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Bibliography on: Invasive Ductal Carcinoma

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 30 Mar 2020 at 01:38 Created: 

Invasive Ductal Carcinoma

Invasive ductal carcinoma (IDC), also known as infiltrating ductal carcinoma, is cancer that began growing in a milk duct and has invaded the fibrous or fatty tissue of the breast outside of the duct. IDC is the most common form of breast cancer, representing 80 percent of all breast cancer diagnoses.

Created with PubMed® Query: ("invasive ductal carcinoma" OR IDC) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2020-03-29

Pareja F, Brown DN, Lee JY, et al (2020)

Whole-Exome Sequencing Analysis of the Progression from Non-Low Grade Ductal Carcinoma In Situ to Invasive Ductal Carcinoma.

Clinical cancer research : an official journal of the American Association for Cancer Research pii:1078-0432.CCR-19-2563 [Epub ahead of print].

PURPOSE: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. Here, we sought to investigate the level of intra-lesion genetic heterogeneity in DCIS and the patterns of clonal architecture changes in the progression from DCIS to invasive disease.

DESIGN: Synchronous DCIS (n=27) and invasive ductal carcinomas of no special type (IDC-NSTs; n=26) from 25 patients and pure DCIS (n=7) from 7 patients were microdissected separately and subjected to high-depth whole-exome (n=56) or massively parallel sequencing targeting ≥410 key cancer-related genes (n=4). Somatic genetic alterations, mutational signatures, clonal composition and phylogenetic analyses were defined using validated computational methods.

RESULTS: DCIS revealed genetic alterations similar to those of synchronously diagnosed IDC-NSTs and of non-related IDC-NSTs from The Cancer Genome Atlas (TCGA), whereas pure DCIS lacked PIK3CA mutations. Clonal decomposition and phylogenetic analyses based on somatic mutations and copy number alterations revealed that the mechanisms of progression of DCIS to invasive carcinoma are diverse, and that clonal selection might have constituted the mechanism of progression from DCIS to invasive disease in 28% (7/25) of patients. DCIS displaying a pattern of clonal selection in the progression to invasive cancer harbored higher levels of intra-lesion genetic heterogeneity than DCIS where no clonal selection was observed.

CONCLUSIONS: Intra-lesion genetic heterogeneity is a common feature in DCIS synchronously diagnosed with IDC-NST. DCIS is a non-obligate precursor of IDC-NST, whose mechanisms of progression to invasive breast cancer are diverse and vary from case to case.

RevDate: 2020-03-28

Greenland NY, Cowan JE, Zhang L, et al (2020)

Expansile cribriform Gleason pattern 4 has histopathologic and molecular features of aggressiveness and greater risk of biochemical failure compared to glomerulation Gleason pattern 4.

The Prostate [Epub ahead of print].

BACKGROUND: Molecular testing of prostate cancer biopsies with Gleason pattern 4 suggests the expansile cribriform pattern is more aggressive than the glomerulation pattern. These two extreme patterns have not been compared at prostatectomy. We hypothesized that at prostatectomy the expansile cribriform pattern would be associated with histopathologic and molecular features of aggressiveness and with greater risk of biochemical recurrence (BCR) than the glomerulation pattern.

METHODS: In a retrospective cohort study, radical prostatectomy reports with expansile cribriform pattern or glomerulation pattern were analyzed for percentage of total pattern 4, extraprostatic extension (EPE), positive lymph nodes, seminal vesicle invasion (SVI), and intraductal carcinoma (IDC). Cases with pattern 5 or with both expansile cribriform and glomerulations patterns present were excluded. The electronic medical record was reviewed for BCR-free survival and for Decipher test results.

RESULTS: Of 1020 radical prostatectomies from July 2015 to July 2018, 110 (11%) had either expansile cribriform or glomerulation pattern present. The expansile cribriform group was associated with more histopathologic features of aggressiveness, with higher average total percentage pattern 4 (43.7 vs 27.0, P = .002), a trend of greater extensive EPE (32.7% vs 17.2%, P = .06), a trend toward statistical significance of higher rate of SVI (11.5% vs 3.4%, P = .1), greater positive lymph nodes (9.6% vs 0%, P = .02), and a higher percentage of cases with or suspicious for IDC (23.1% vs 8.6%, P = .04). The risk of BCR was 4.4 (1.3-15.4) fold greater for the expansile cribriform group vs the glomerulations group (P = .02). For the 38 patients who underwent Decipher testing, the expansile cribriform group had a high-risk assay category mean score whereas the glomerulations group had an average risk assay category mean score (0.61 vs 0.47, P = .02).

CONCLUSIONS: In a comparison of prostatectomy cases with expansile cribriform pattern to those with glomerulation pattern, the expansile cribriform pattern was associated with more histopathologic features of aggressiveness, greater risk of biochemical failure, and higher scores with a molecular classifier (Decipher) test. These findings underscore the importance of reporting the types of pattern 4 and supports the argument that men with expansile cribriform likely require more aggressive management.

RevDate: 2020-03-27

Frasson AL, Lichtenfels M, de Souza AAB, et al (2020)

Risk-reducing mastectomy: a case series of 124 procedures in Brazilian patients.

Breast cancer research and treatment pii:10.1007/s10549-020-05582-w [Epub ahead of print].

PURPOSE: Women with mutations in breast cancer predisposition genes have a significantly higher lifetime risk of developing breast cancer and can opt for risk-reducing mastectomy. Women with positive family history of cancer can also opt for prophylactic surgery as a preventive method in selected cases. Current studies showed reduced risk of developing breast cancer after prophylactic nipple-sparing mastectomy, however, despite the good clinical outcomes, one of the main concerns regarding nipple-sparing mastectomy (NSM) is the oncological safety of nipple-areola complex preservation. In this study, we aimed to evaluate the indications, complication rates, and unfavorable events of 62 Brazilian patients that underwent risk-reducing NSM from 2004 to 2018.

METHODS: Patient data were reviewed retrospectively and descriptive statistics were utilized to summarize the findings.

RESULTS: The mean patients age was 43.8 years. The main indication for risk-reducing NSM was the presence of pathogenic mutation (53.3%), followed by atypia or lobular carcinoma in situ (25.8), and family history of breast cancer and/or ovarian cancer (20.9%). There were four (3.2%) incidental diagnosis of ductal carcinoma in situ and one invasive ductal carcinoma (0.8%). From the 124 prophylactic NSM performed, two (1.6%) complications had occurred: one (0.8%) infection and one (0.8%) partial nipple necrosis. In a mean follow-up of 50 months, there was one (1.6%) newly diagnosed breast cancer in the 62 patients undergoing prophylactic NSM.

CONCLUSIONS: Our findings demonstrated efficacy and safety to perform NSM as prophylactic surgery with good oncological outcomes and low complication rates in a case series of Brazilian patients.

RevDate: 2020-03-27

Louie RJ, Gaber CE, Strassle PD, et al (2020)

Trends in Surgical Axillary Management in Early Stage Breast Cancer in Elderly Women: Continued Over-Treatment.

Annals of surgical oncology pii:10.1245/s10434-020-08388-8 [Epub ahead of print].

INTRODUCTION: In the past two decades, three prospective randomized trials demonstrated that elderly women with early stage hormone positive breast cancer had equivalent disease-specific mortality regardless of axillary surgery. In 2016, the Choosing Wisely campaign encouraged patients and providers to reconsider the role of axillary surgery in this population. We sought to identify factors that contribute to adopting non-operative management of the axilla in these patients.

MATERIALS AND METHODS: We performed a retrospective analysis of women ≥ 70 years old with cT1/T2, hormone positive invasive ductal carcinoma who underwent partial or total mastectomy, with/without axillary surgery, and did not receive adjuvant chemotherapy from the National Cancer Database from 2004 to 2015. We used multivariable log-binomial regression to model the risk of undergoing axillary surgery across region, care setting, and Charlson-Deyo scores, and analyzed temporal trends using Poisson regression. From 2004 to 2015, 87,342 of 99,940 women who met inclusion criteria (83%) had axillary surgery. Over time, axillary surgery increased from 78% to 88% (p < 0.001). This rise was consistent across region (p = 0.81) and care setting (p = 0.09), but flattened as age increased (p < 0.001). Omitting axillary surgery was more likely in patients treated in New England (RR 0.88, 95% CI 0.86, 0.89) and patients ≥ 85 (RR 0.66, 95% CI 0.65, 0.67).

CONCLUSIONS: Axillary surgery continues to be the preferred option of axillary management in elderly women with early stage, clinically node negative, hormone-positive, invasive breast cancer despite no survival benefit. Identifying factors to improve patient selection and dissemination of current recommendations can improve adoption of current evidence on axillary surgery in the elderly.

RevDate: 2020-03-27

Ma S, Lv Y, R Ma (2020)

Prognostic Significance of Metastatic Lymph Nodes Ratio (MLNR) Combined with Protein-Tyrosine Phosphatase H1 (PTPH1) Expression in Operable Breast Invasive Ductal Carcinoma.

Cancer management and research, 12:1895-1901 pii:239085.

Purpose: The metastatic lymph node ratio (MLNR) is one of the most important factors in prognostic analysis of breast cancer. The objective of this study was to determine if MLNR combined with protein-tyrosine phosphatase H1 (PTPH1) pathological expression can be used to predict the prognosis of patients with breast invasive ductal carcinoma (IDC) better than one factor only.

Patients and Methods: A total of 136 patients with invasive ductal carcinoma (IDC) of breast who underwent modified radical mastectomy and were treated with chemotherapy after operation at Qilu Hospital of Shandong University from December 2008 to October 2011 were included. PTPH1 expression was evaluated by immunohistochemistry in surgical specimens retrospectively collected from patients with histologically proven invasive ductal breast cancer. Kaplan-Meier survival analysis and Cox regression analysis were performed to assess the prognostic significance of PTPH1 expression. A prognostic factor for disease-free survival (DFS) was identified by univariate and multivariate analyses. ROC analysis was used to evaluate the performance of single factors and combined feature.

Results: One hundred and thirty-six patients were included in the analysis. By cut-point survival analysis, MLNR cut-off was designed as 0.2. On multivariate analysis, a MLNR>0.2 was associated with a worse DFS (HR=2.581, 95% CI=1.303-5.113, P=0.007). PTPH1 overexpression is correlated with a better DFS (HR=0.391, 95% CI=0.162-0.945, P=0.037). In addition, MLNR and PTPH1 combined feature had better performance in predicting clinical outcomes after surgery long before recurrence had occurred (Area under the curve=0.795 [95% CI=0.694-0.896], P<0.001).

Conclusion: These findings indicate that both PTPH1 and MLNR are accurate independent prognostic parameters in patients with IDC of the breast. Better information on IDC prognosis could be obtained from the combined feature.

RevDate: 2020-03-27

Patel M, Li C, Aronson JH, et al (2020)

The effect of post mastectomy radiation therapy on survival in breast cancer patients with N1mic disease.

Breast (Edinburgh, Scotland), 51:50-56 pii:S0960-9776(20)30066-7 [Epub ahead of print].

BACKGROUND: The role of post mastectomy radiation therapy (PMRT) in patients with N1mic breast cancer has not been well defined. A retrospective analysis was performed using the SEER database to evaluate the impact of PMRT on survival in patients with N1mic breast cancer.

MATERIALS AND METHODS: Women with T1-T2, N1mic, M0 breast cancer who had undergone mastectomy were analyzed. Descriptive statistics were calculated for all variables. Univariate analysis to assess for differences in survival with respect to covariates was performed using the log rank test while multivariate analysis was performed with Cox proportional hazards regression. Sub-cohort analysis with propensity score matching was used to assess differences in survival among patients undergoing PMRT vs no PMRT. Comparisons were considered statistically significant at P < 0.05.

RESULTS: Among 5878 patients, 1202 (20%) underwent PMRT. On univariate analysis, PMRT was a significant predictor of CSS, but not OS. There was no difference in either OS or CSS between the PMRT vs no PMRT groups on multivariate Cox regression analysis and after propensity score matching.

CONCLUSIONS: Among patients with T1-T2, N1mic, M0 breast IDC from the SEER database, there was no difference in either OS or CSS among patients who underwent PMRT vs no PMRT. These results suggest that PMRT does not impact survival among breast cancer patients with N1mic disease. However, additional prospective studies with longer follow up are necessary for further evaluation.

RevDate: 2020-03-27

Rasmy A, Y Sorour (2020)

Effect of Obesity on Neoadjuvant Systemic Therapy Outcomes in Patients with Early Breast Cancer: A Retrospective Institutional Study.

Asian Pacific journal of cancer prevention : APJCP, 21(3):683-691.

BACKGROUND: Obesity and overweight are usually considered as poor prognostic factors in early breast cancer. Body mass index (BMI) is a significant predictive factor for lower pathologic complete response (pCR) rates after neo-adjuvant systemic therapy (NST). The relationship between obesity and breast cancer prognosis varies according to patient and tumor characteristics such as menopausal status and tumor subtype, respectively.

PATIENTS AND METHODS: Between March 2010 and October 2013, 80 patients with early breast cancer who had received standard NST from KFSH Saudi Arabia were included in this study. For statistical analysis, the study participants were categorized into two groups based on their BMI, as normal (BMI < 25 kg/m2) and obese groups (BMI ≥ 25 kg/m2). pCR was defined as non-invasive cancer in the breast/axillary tissue.

RESULTS: The median age of our patients was 48 (range, 38-68) years. Invasive ductal carcinoma (IDC) subtype was identified in 93.8% of the cases. Additionally, 26 (32.5%) and 33 (41.25%) patients were diagnosed with stage II and stage IIIA breast cancer, respectively. Lymphovascular invasion was detected in 32.5%, whereas intermediate and high-grade malignancy were found in 61.25% and 32.5% of the patients, respectively. Forty-four patients (55%) were obese. pCR was achieved in 56 patients (70%), and the comparison between patients with and without pCR revealed that those in the former group had significantly lower tumor grades. Significantly, lower relapse and mortality rates were distinguished in patients who achieved pCR than in those who did not. Additionally, comparison between normal and obese patients revealed that a high number of patients in both groups were post-menopausal (p = 0.001). However, survival analysis indicated the absence of significant differences in disease-free survival between the two groups based on BMI (p = 0.19). Conversely, patients with normal BMI had significantly better overall survival than obese patients (p = 0.029), with a higher mortality rate noted in the obese group (16.7% vs 2.3%, p = 0.037).

CONCLUSIONS: In the present study, 58.3% of patients that failed to achieve pCR had BMI above the normal level; they moreover had higher relapse rates and lower survival compared with normal BMI patients. This finding needs to be verified through further prospective studies to determine if BMI is a risk factor for breast cancer.

RevDate: 2020-03-26

Chelban V, Carecchio M, Rea G, et al (2020)

MYORG-related disease is associated with central pontine calcifications and atypical parkinsonism.

Neurology. Genetics, 6(2):e399 pii:NG2019011999.

Objective: To identify the phenotypic, neuroimaging, and genotype-phenotype expression of MYORG mutations.

Methods: Using next-generation sequencing, we screened 86 patients with primary familial brain calcification (PFBC) from 60 families with autosomal recessive or absent family history that were negative for mutations in SLC20A2, PDGFRB, PDGBB, and XPR1. In-depth phenotyping and neuroimaging investigations were performed in all cases reported here.

Results: We identified 12 distinct deleterious MYORG variants in 7 of the 60 families with PFBC. Overall, biallelic MYORG mutations accounted for 11.6% of PFBC families in our cohort. A heterogeneous phenotypic expression was identified within and between families with a median age at onset of 56.4 years, a variable combination of parkinsonism, cerebellar signs, and cognitive decline. Psychiatric disturbances were not a prominent feature. Cognitive assessment showed impaired cognitive function in 62.5% of cases. Parkinsonism associated with vertical nuclear gaze palsy was the initial clinical presentation in 1/3 of cases and was associated with central pontine calcifications. Cerebral cortical atrophy was present in 37% of cases.

Conclusions: This large, multicentric study shows that biallelic MYORG mutations represent a significant proportion of autosomal recessive PFBC. We recommend screening MYORG mutations in all patients with primary brain calcifications and autosomal recessive or negative family history, especially when presenting clinically as atypical parkinsonism and with pontine calcification on brain CT.

RevDate: 2020-03-26

Cai SM, Wang HY, Zhang XY, et al (2020)

The Vascular Index of Superb Microvascular Imaging Can Improve the Diagnostic Accuracy for Breast Imaging Reporting and Data System Category 4 Breast Lesions.

Cancer management and research, 12:1819-1826 pii:242101.

Purpose: To investigate whether the vascular index (VI) of superb microvascular imaging (SMI) could improve the diagnostic efficiency for BI-RADS 4 breast lesions and reduce the number of unnecessary biopsies.

Patients and Methods: For this study, we selected 222 consecutive BI-RADS 4 breast lesions detected by ultrasound and confirmed by pathology from January 2016 to October 2018. A VI of 4.0 was set as the cutoff value to degrade BI-RADS classification. We calculated the accuracy, sensitivity and PPV of a BI-RADS diagnosis alone and the combination of BI-RADS and the VI.

Results: Pathologically, of the 222 lesions, 129 were confirmed to be benign, and 93 were found to be malignant. A VI of 4.0 was set as the cutoff value; when the VI≤4.0, those BI-RADS 4 masses were downgraded one level (4C-4B, 4B-4A, 4A-3) to an integral BI-RADS grade, while the others maintained the conventional grade. A total of 54 BI-RADS 4 lesions were degraded to BI-RADS 3, including 53 benign lesions and 1 malignant lesion. The diagnostic accuracy (65.3% vs 41.9%) and PPV (54.8% vs 41.9%) were significantly improved. The sensitivity decreased slightly (98.9% vs 100%) because 1 of the 54 downgraded BI-RADS 4 lesions, which had a pathological type of invasive ductal carcinoma, was incorrectly downgraded.

Conclusion: SMI is a noninvasive tool for visualizing the vascular structure with high-resolution microvascular images. As a quantitative index, the VI can be used to appropriately downgrade benign lesions classified as BI-RADS 4, which can improve the diagnostic accuracy and PPV and reduce unnecessary biopsies.

RevDate: 2020-03-26

Yap RV, FM De La Serna (2020)

Outcomes of Sentinel Lymph Node Biopsy Using Blue Dye Method for Early Breast Cancer - A Single-Institution Experience in the Philippines.

Breast cancer (Dove Medical Press), 12:37-44 pii:242115.

Purpose: This study aimed to share our experience with SLNB in the Filipino population with early breast cancer.

Patients and Methods: A retrospective review was done on all patients with confirmed invasive breast carcinoma, tumor size of 5 cm or less (T1/T2), who preoperatively had no clinical signs of axillary metastasis and subsequently underwent SLNB with blue dye method from January 01, 2008 to December 31, 2017. Clinicopathologic profiles were recorded. Outcomes of patients who had SLNB only were assessed.

Results: One hundred twenty-nine patients matched the inclusion criteria with a mean age of 54.3 years. The majority (88.4%) had a total mastectomy. Invasive ductal carcinoma (65.1%) was the most common tumor. Estrogen and progesterone receptors were positive in 69% and 61.2% respectively while only 28.7% were HER2 positive. SLNB was successfully carried out in 126 (97.7%) patients with a range of 2-4 SLNs harvested. Thirty-four (26.4%) patients had completion ALND. With a median of 25 months follow-up, 75 out of 95 patients who underwent SLNB alone had follow-up data. Forty-six (61.3%) patients had seroma formation. One (1.3%) patient developed arm paresthesia, 2 (2.7%) local (chest wall) and 2 (2.7%) axillary recurrences after a negative SLNB. None of the patients developed lymphedema.

Conclusion: The blue dye method alone is acceptable and can be readily employed in institutions with limited resources. Even with the limited population, the morbidity and oncologic outcomes of patients who underwent SLNB alone were low and comparable to similar international published data. SLNB should be the preferred method for staging the axilla.

RevDate: 2020-03-26

Liu Q, Zhang J, Kulkarni HR, et al (2020)

177Lu-DOTATOC Peptide Receptor Radionuclide Therapy in a Patient With Neuroendocrine Breast Carcinoma and Breast Invasive Ductal Carcinoma.

Clinical nuclear medicine [Epub ahead of print].

Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)-targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on Ga-DOTATOC PET/CT, and remarkably partial remission after Lu-DOTATOC PRRT.

RevDate: 2020-03-24

Liu W, Zhang R, Ling Y, et al (2020)

Automatic recognition of breast invasive ductal carcinoma based on terahertz spectroscopy with wavelet packet transform and machine learning.

Biomedical optics express, 11(2):971-981 pii:381623.

We demonstrate an automatic recognition strategy for terahertz (THz) pulsed signals of breast invasive ductal carcinoma (IDC) based on a wavelet entropy feature extraction and a machine learning classifier. The wavelet packet transform was implemented into the complexity analysis of the transmission THz signal from a breast tissue sample. A novel index of energy to Shannon entropy ratio (ESER) was proposed to distinguish different tissues. Furthermore, the principal component analysis (PCA) method and machine learning classifier were further adopted and optimized for automatic classification of the THz signal from breast IDC sample. The areas under the receiver operating characteristic curves are all larger than 0.89 for the three adopted classifiers. The best breast IDC recognition performance is with the precision, sensitivity and specificity of 92.85%, 89.66% and 96.67%, respectively. The results demonstrate the effectiveness of the ESER index together with the machine learning classifier for automatically identifying different breast tissues.

RevDate: 2020-03-24

Boltežar L, Gašljević G, Novaković S, et al (2020)

An interesting case of likely BRCA2 related bilateral breast cancer with metastasis in the fimbrial part of fallopian tube.

Hereditary cancer in clinical practice, 18:7 pii:139.

Background: In a patient with a germline BRCA2 pathogenic variant with breast cancer, an adnexal mass can represent either a metachronous primary tumor or a metastasis of the breast cancer. A clear distinction between those two possibilities is crucial since treatments differ substantially and so does survival of the patient.

Case presentation: We present a case of a 47-year-old patient with bilateral breast carcinoma with a germline BRCA2 pathogenic variant. The first manifestation of the disease was a lump in her left breast in 1998, histological report was invasive ductal carcinoma, triple-negative. She was treated with surgery, chemotherapy and radiotherapy. In 2011 a new occult carcinoma was found in her right axilla, however the specimen was estrogen receptor (ER) and progesterone receptor (PgR) positive. She was treated as a new primary occult carcinoma of the right breast with surgery, radiotherapy and adjuvant hormonal treatment. In 2016 a mass in the left adnexa was found with imaging techniques. She underwent surgery as if it was primary ovarian cancer, yet histology revealed it was a metastasis of a triple-negative breast carcinoma in the fimbrial part of the left Fallopian tube. She received adjuvant chemotherapy after surgery and is now in complete remission.

Conclusion: We present an interesting and quite rare case of two primary breast carcinomas in a patient with a known BRCA2 pathogenic variant with metastasis in the fimbrial part of the left Fallopian tube. We conclude that there were two primary breast tumours and the one from 2011 spread into the fimbrial part of the left Fallopian tube in 2016. Despite the fact that molecular analyses could not confirm the joint tumour origin, we believe that there was a receptor status conversion over time explaining different receptor status. The possibility of a triple-negative metastasis from the tumour treated in 1998 is less probable. With both of aforementioned possibilities being prognostically unfavourable, the patients' outcome is so far excellent and she was in complete remission at the time of writing this article.

RevDate: 2020-03-24

Shah T, Shah N, Vijay DG, et al (2020)

Male Breast Cancer: Current Trends-a Tertiary Care Centre Experience.

Indian journal of surgical oncology, 11(1):7-11.

Male breast cancer is a rare tumour in all parts of the world. About 1% of all breast cancers occur in men. Occurrence of male breast cancer peaks at age 71 years. Familial cases usually have BRCA2 rather than BRCA1 mutations. Presentation is usually a lump or nipple inversion, but is often late, with more than 40% of individuals having stage III or IV disease. We retrospectively reviewed 25 male patients with breast cancer who came to the HCG Cancer Centre, Ahmedabad between 2014 and 2018, and their demographic details, tumor profile, and radiological, histopathological as well as luminal profile findings were studied. The average age at presentation and detection of male breast cancer was 61.08 years. Incidence of male ca. breast over these 4 years was 4.75/year which had a significant increase compared with our own data in the last 8 years (3/year). Male to female ratio for ca. breast was 1:61. One out of 25 (4%) patients had gynaecomastia. The most common histology was invasive ductal carcinoma-not otherwise specified with none of the patients having lobular carcinoma. Majority of patients were ER/PR positive and HER-2 negative. Male breast cancer is having a rising incidence, which in our study is 1.56%. Males have relatively older age at presentation and stage-by-stage treatment remains the same. Males are more likely to be having prognostically favourable luminal subtypes. Male breast cancer in Indian population is currently experiencing an increasing trend. Improved awareness amongst patients and high index of suspicion by the clinicians along with accurate diagnostic techniques help detect the disease at an earlier stage culminating into prolonged overall and disease-free survival.

RevDate: 2020-03-24

Bao J, Markovic T, Brancato L, et al (2020)

Novel Fabrication Process for Integration of Microwave Sensors in Microfluidic Channels.

Micromachines, 11(3): pii:mi11030320.

This paper presents a novel fabrication process that allows integration of polydimethylsiloxane (PDMS)-based microfluidic channels and metal electrodes on a wafer with a micrometer-range alignment accuracy. This high level of alignment accuracy enables integration of microwave and microfluidic technologies, and furthermore accurate microwave dielectric characterization of biological liquids and chemical compounds on a nanoliter scale. The microfluidic interface between the pump feed lines and the fluidic channels was obtained using magnets fluidic connection. The tube-channel interference and the fluidic channel-wafer adhesion was evaluated, and up to a pressure of 700 mBar no leakage was observed. The developed manufacturing process was tested on a design of a microwave-microfluidic capacitive sensor. An interdigital capacitor (IDC) and a microfluidic channel were manufactured with an alignment accuracy of 2.5 μm. The manufactured IDC sensor was used to demonstrate microwave dielectric sensing on deionized water and saline solutions with concentrations of 0.1, 0.5, 1, and 2.5 M.

RevDate: 2020-03-23

Szentirmai E, GA Giannico (2020)

Intraductal carcinoma of the prostate.

Pathologica, 112(1):17-24.

Intraductal carcinoma of the prostate (IDC-P) is a diagnostic entity characterized by architecturally or cytologically malignant-appearing prostatic glandular epithelium confined to prostatic ducts. Despite its apparent in situ nature, this lesion is associated with aggressive prostatic adenocarcinoma and is a predictor for poor prognosis when identified on biopsy or radical prostatectomy. This review discusses diagnosis, clinical features, histogenesis, and management of IDC-P, as well as current research and controversies surrounding this entity.

RevDate: 2020-03-23

Manthri S, Sharma P, Mejbel HA, et al (2020)

Third Line Eribulin for Triple-negative Metastatic Breast Ductal Carcinoma Resulting in Extended Progression-free Survival of 57 Months.

Cureus, 12(2):e6980.

Eribulin is a non-taxane microtubule inhibitor approved for the treatment of metastatic breast carcinoma after two prior chemotherapeutic regimens. We report a patient with extended progression-free survival (PFS) of more than 57 months with metastatic breast carcinoma treated with eribulin in the third-line setting. A 48-year-old lady was diagnosed with stage IIA (pT2N0M0), high grade, triple-negative, invasive ductal carcinoma (IDC) of the left breast on core needle biopsy. She underwent neoadjuvant chemotherapy with adriamycin, and cyclophosphamide followed by a negative sentinel lymph node (SLN) biopsy. Subsequent mastectomy and axillary lymph node dissection revealed a 2.5 cm, high grade, triple-negative IDC with three additional lymph nodes negative for metastatic carcinoma, consistent with the initial diagnosis. Eight months into the surveillance program, the patient developed a 2.8 cm right lower lobe (RLL) lung mass with standard uptake value (SUV) of 27 on positron emission tomography-computed tomography (PET/CT). Core needle biopsy of the lung lesion revealed sheets of poorly differentiated carcinoma, immunophenotypically compatible with the initial diagnosis of breast pathology. She then commenced single-agent paclitaxel in the 1st line metastatic setting with a significant decrease in RLL lung mass to less than 1 cm with an SUV of 1.7 noted. The patient developed progression after seven months and started 2nd line gemcitabine noting initial improvement and subsequent stable disease for a period of 12 months. Eventual progression of RLL lung nodule measuring 2.1 cm with SUV of 10 noted. Initiated 3rd line eribulin with a notable response on imaging studies within three months and with no evidence of disease (NED) on scans over the subsequent 57 months. Eribulin related mild neuropathy superimposed on previous paclitaxel associated grade 2 neuropathy required a 20% eribulin dose reduction. The patient is currently clinically and radiographically stable with plateaued serum tumor markers. Our patient has shown excellent response and tolerance to eribulin with PFS of over 57 months (nineteen times the norm) which is rare.

RevDate: 2020-03-21

Bao J, Maenhout G, Markovic T, et al (2020)

A Microwave Platform for Reliable and Instant Interconnecting Combined with Microwave-Microfluidic Interdigital Capacitor Chips for Sensing Applications.

Sensors (Basel, Switzerland), 20(6): pii:s20061687.

This work presents a novel platform conceived as an interconnect box (ICB) that brings high-frequency signals from microwave instruments to consumable lab-on-a-chip devices. The ICB can be connected to instruments with a standard coaxial connector and to consumable chips by introducing a spring-levered interface with elastomer conductive pins. With the spring-system, microwave-microfluidic chips can be mounted reliably on the setup in a couple of seconds. The high-frequency interface within the ICB is protected from the environment by an enclosure having a single slit for mounting the chip. The stability and repeatability of the contact between the ICB and inserted consumable chips are investigated to prove the reliability of the proposed ICB. Given the rapid interconnecting of chips using the proposed ICB, five different interdigital capacitor (IDC) designs having the same sensing area were investigated for dielectric permittivity extraction of liquids. The designed IDCs, embedded in a polydimethylsiloxane (PDMS) channel, were fabricated with a lift-off gold patterning technology on a quartz substrate. Water-Isopropanol (IPA) mixtures with different volume fractions were flushed through the channel over IDCs and sensed based on the measured reflection coefficients. Dielectric permittivity was extracted using permittivity extraction techniques, and fitted permittivity data shows good agreement with literature from 100 to 25 GHz.

RevDate: 2020-03-20

Kader T, Elder K, Zethoven M, et al (2020)

The genetic architecture of breast papillary lesions as a predictor of progression to carcinoma.

NPJ breast cancer, 6:9 pii:150.

Intraductal papillomas (IDP) are challenging breast findings because of their variable risk of progression to malignancy. The molecular events driving IDP development and genomic features of malignant progression are poorly understood. In this study, genome-wide CNA and/or targeted mutation analysis was performed on 44 cases of IDP, of which 20 cases had coexisting ductal carcinoma in situ (DCIS), papillary DCIS or invasive ductal carcinoma (IDC). CNA were rare in pure IDP, but 69% carried an activating PIK3CA mutation. Among the synchronous IDP cases, 55% (11/20) were clonally related to the synchronous DCIS and/or IDC, only one of which had papillary histology. In contrast to pure IDP, PIK3CA mutations were absent from clonal cases. CNAs in any of chromosomes 1, 16 or 11 were significantly enriched in clonal IDP lesions compared to pure and non-clonal IDP. The observation that 55% of IDP are clonal to DCIS/IDC indicates that IDP can be a direct precursor for breast carcinoma, not limited to the papillary type. The absence of PIK3CA mutations and presence of CNAs in IDP could be used clinically to identify patients at high risk of progression to carcinoma.

RevDate: 2020-03-20

Shiino S, Yoshida M, Tokura M, et al (2020)

Locally advanced triple negative breast cancer arising from fibroadenoma with complete response to neoadjuvant chemotherapy: A case report.

INTRODUCTION: Breast cancer arising from benign fibroadenoma (FA) is rare. The histological type of the former was either carcinoma in situ or early-stage invasive breast carcinoma with hormone receptor positive/HER2 (human epidermal growth factor receptor-2)-negative phenotype. Meanwhile, advanced breast cancer of triple negative (TN) phenotype such as our case is extremely uncommon and clinically challenging.

PRESENTATION OF CASE: We experienced a case of a 53-year-old woman that had invasive ductal carcinoma of TN phenotype in FA with multiple lymph node metastases. After receiving neoadjuvant chemotherapy (NAC), she underwent breast mastectomy and axillary dissection. The pathological examination on postoperative specimens revealed the dense fibrous stroma in the FA without any residual viable tumor cells and was considered as pathological complete response (pCR).

DISCUSSION: This is the first report presenting a case of NAC treatment for invasive ductal carcinoma (IDC) in FA. Furthermore, the patient achieved pCR even if IDC was located within FA. Diagnosing breast cancer in FA may be challenging as the carcinoma component may be hidden by the FA component. If imaging of FA became larger or abnormal changes during follow-up examinations, needle biopsy should be recommended for assessment of the lesion positively.

CONCLUSION: This is the first report presenting a case of advanced breast cancer in FA of TN phenotype with multiple lymph node metastases who achieved pCR even if IDC was located within FA.

RevDate: 2020-03-19

Lee RA, Vo DT, Zurko JC, et al (2020)

Infectious Diseases Consultation Is Associated With Decreased Mortality in Enterococcal Bloodstream Infections.

Open forum infectious diseases, 7(3):ofaa064 pii:ofaa064.

Background: Enterococcus species frequently cause health care-associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown.

Methods: This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients >18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture.

Results: Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P < .001), echocardiography (79% vs 45%; P < .001), surgical intervention (20% vs 7%; P = 0.01), and have appropriate antibiotic duration (90% vs 46%; P < .001). Thirty-day mortality was significantly higher in the no-IDC group (27 % vs 12 %; P < .007). In multivariate analysis, 30-day in-hospital mortality was associated with both E. faecium bacteremia (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.09-5.23) and IDC (aOR, 0.35; 95% CI, 0.16-0.76).

Conclusions: Patients who received IDC for Enterococcus bacteremia had significantly lower 30-day mortality. Further prospective studies are necessary to determine if these outcomes can be validated in other institutions for patients who receive IDC with Enterococcus bacteremia.

RevDate: 2020-03-19

Ibrahim ME, Saleh M, Ali A, et al (2020)

Multiple Primary Malignant Neoplasms: An Unusual Case of Metachronous Breast Ductal and Squamous Cell Carcinomas.

Cureus, 12(2):e6954.

Multiple primary malignant neoplasms (MPMN) are generally defined as the co-occurrence of multiple primary malignant neoplasms of distinct histology in the same individual. Second and higher-order primary malignancies now comprise about 18% of all incidence of cancer in the USA. The incidence ratio of developing multiple primary cancers (MPCs) in female cancer survivors is 1.17 to 1.6. In women with breast cancer, the incidence ratio is even higher, according to age at diagnosis of breast cancer. However, the concurrence of breast cancer and squamous cell carcinoma is not described in the literature. Primary squamous cell carcinoma of bone is also rare in the skeletal system other than in the skull, with only three such cases reported in the English literature. We present a case of a 59-year-old woman with high-grade primary invasive ductal carcinoma of the breast and second distinct squamous cell carcinoma metastasis to the bone of unknown primary site. A search for a primary squamous cell carcinoma, including CT head and neck, CT chest, colposcopy, esophagogastroduodenoscopy (EGD) and colonoscopy, did not show any evidence of a primary site.

RevDate: 2020-03-19

Young CR, Harigopal M, D Pucar (2020)

Rapid progression of carcinoma en cuirasse breast dermal metastases on 18F-fludeoxyglucose positron emission tomography-computed tomography.

World journal of nuclear medicine, 19(1):65-68 pii:WJNM-19-65.

Cancer in the dermis of the breast has a poor prognosis. The breast dermis can become malignantly involved primarily in inflammatory breast cancer, through the direct extension of locally advanced breast cancer, or metastatically from an underlying breast mass or a distant primary malignancy (e.g., gastric adenocarcinoma). Breast dermal metastases have the shortest median survival among them. Breast dermal metastases are classified into eight clinicohistopathologic groups, one of which is carcinoma en cuirasse. We present a case of a 52-year-old female with a history of invasive ductal carcinoma, Stage IIIC (pT2N3a), treated with lumpectomy, axillary node dissection, and chemoradiation therapy that recurred as carcinoma en cuirasse breast dermal metastases. Through 18F-fludeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) and clinical images, the case illustrates the rapid progression and devastating consequences of carcinoma en cuirasse breast dermal metastases over a 4-month period despite optimal therapy. Furthermore, the case emphasizes the sensitivity of 18F-FDG PET-CT to detect pathology in the breast dermis. Finally, the case highlights the crucial role that nuclear medicine physicians play in helping clinical colleagues differentiate between the various breast dermal malignant manifestations and benign mastitis, a common confounder in postradiation patients.

RevDate: 2020-03-18

Hasan SS, Jabs M, Taylor J, et al (2020)

Endothelial Notch signaling controls insulin transport in muscle.

EMBO molecular medicine [Epub ahead of print].

The role of the endothelium is not just limited to acting as an inert barrier for facilitating blood transport. Endothelial cells (ECs), through expression of a repertoire of angiocrine molecules, regulate metabolic demands in an organ-specific manner. Insulin flux across the endothelium to muscle cells is a rate-limiting process influencing insulin-mediated lowering of blood glucose. Here, we demonstrate that Notch signaling in ECs regulates insulin transport to muscle. Notch signaling activity was higher in ECs isolated from obese mice compared to non-obese. Sustained Notch signaling in ECs lowered insulin sensitivity and increased blood glucose levels. On the contrary, EC-specific inhibition of Notch signaling increased insulin sensitivity and improved glucose tolerance and glucose uptake in muscle in a high-fat diet-induced insulin resistance model. This was associated with increased transcription of Cav1, Cav2, and Cavin1, higher number of caveolae in ECs, and insulin uptake rates, as well as increased microvessel density. These data imply that Notch signaling in the endothelium actively controls insulin sensitivity and glucose homeostasis and may therefore represent a therapeutic target for diabetes.

RevDate: 2020-03-17

Bianchi A, Pozza S, Giovannacci L, et al (2020)

Phlegmasia Cerulea Dolens in a Patient with Breast Cancer and Inferior Vena Cava Hypoplasia.

Case reports in vascular medicine, 2020:2176848.

Background: No clear guidelines exist for the management of phlegmasia cerulea dolens. This case report shows how a hybrid approach might be successful. It also shows how rare pathologies can combine to create a life- and limb-threatening condition. Case Presentation. A 75-year-old man, known for nephrotic syndrome currently under investigation, presented to the emergency department with a 24-hour history of left leg swelling followed by intense pain. The left lower limb showed a phlegmasia cerulean dolens. Renal function, coagulation profile, and inflammatory parameters were normal; D-Dimers 5,6 mg/L. The CT scan showed juxtarenal thrombosis of the hypoplastic IVC, involving both renal veins, reaching the left iliac-femoral-popliteal axis, with collateralization to the pelvic and mesenteric veins, associated with bilateral segmental pulmonary embolisms. A suspected left breast nodule was also found. Intravenous heparin was immediately administered, and urgent hybrid procedure with surgical thrombectomy and venous angiography and thromboaspiration, liberating the iliolumbar collaterals, was performed. A lateral leg fasciotomy was mandatory due to the phlegmasia cerulea. Postoperative Doppler US showed a good venous compressibility of the left leg. Thrombophilia screening was negative. The breast nodule was biopsied showing an invasive ductal carcinoma. The patient was discharged with oral rivaroxaban and indication for left mastectomy and oncological therapy with aromatase inhibitors.

Conclusion: This case highlights the dramatic consequence of different risk factors for venous thromboembolism as cancer and nephrotic syndrome in a patient with hypoplasia of the inferior cava vein. Venous thromboaspiration has been used in order to timely recanalize important collaterals. Phlegmasia cerulea dolens was resolved after the procedure and lateral calf fasciotomy. Further evidence is needed to clearly define the role of venous thromboaspiration in the treatment of complex proximal deep venous thrombosis of the lower extremity.

RevDate: 2020-03-17

Fernández-Nogueira P, Mancino M, Fuster G, et al (2020)

Breast Mammographic Density: Stromal Implications on Breast Cancer Detection and Therapy.

Journal of clinical medicine, 9(3): pii:jcm9030776.

Current evidences state clear that both normal development of breast tissue as well as its malignant progression need many-sided local and systemic communications between epithelial cells and stromal components. During development, the stroma, through remarkably regulated contextual signals, affects the fate of the different mammary cells regarding their specification and differentiation. Likewise, the stroma can generate tumour environments that facilitate the neoplastic growth of the breast carcinoma. Mammographic density has been described as a risk factor in the development of breast cancer and is ascribed to modifications in the composition of breast tissue, including both stromal and glandular compartments. Thus, stroma composition can dramatically affect the progression of breast cancer but also its early detection since it is mainly responsible for the differences in mammographic density among individuals. This review highlights both the pathological and biological evidences for a pivotal role of the breast stroma in mammographic density, with particular emphasis on dense and malignant stromas, their clinical meaning and potential therapeutic implications for breast cancer patients.

RevDate: 2020-03-16

Palacios-Fuenmayor LJ, Naranjo-Isaza AM, Serna-Ortiz CA, et al (2020)

Evaluation of the pathologic response to neoadjuvant treatment in rectal cancer. Experience at the Instituto de Cancerología de Medellín (Colombia, 2011-2017).

Revista de gastroenterologia de Mexico pii:S0375-0906(20)30012-4 [Epub ahead of print].

INTRODUCTION AND AIMS: Neoadjuvant therapy in rectal cancer is associated with a decrease in tumor size and is the therapeutic indication for patients with T3 or T4 tumors or lymph node involvement. Our aim was to describe the frequency of pathologic response and the survival rate in patients that underwent neoadjuvant therapy for rectal cancer.

MATERIALS AND METHODS: A retrospective follow-up study with a survival analysis was conducted. Patients with locally advanced rectal cancer that received neoadjuvant treatment and were operated on at the Instituto de Cancerología Las Américas (Medellín, Colombia) were analyzed. Survival was calculated using the Kaplan-Meier method.

RESULTS: A total of 152 patients were included. Mean patient age was 59 years (12.8 SD), 53.9% were men, and 58.6% of the patients were diagnosed with stage IIIB disease. The pathologic complete response (pCR) was achieved in 17% of the patients. A total of 146 (96.1%) patients received the chemoradiotherapy protocol. Fifty-two (34.2%) patients developed metastasis and/or relapse, and one (3.8%) of those patients had presented with pCR. The median follow-up period was 33 months (Q1-Q3: 20-45), with an overall survival rate of 79.5% (95% CI 70.9-85.8). The 5-year survival rate for the patients that had pCR was 80% (95% CI 20.3-96.9).

CONCLUSIONS: The frequency of pCR was similar to that in other published studies and disease recurrence was lower, compared with patients with no response. The 5-year survival rate in patients with pCR was high, albeit lower than that reported in other studies.

RevDate: 2020-03-15

Ye F, Yu P, Li N, et al (2020)

Prognosis of invasive micropapillary carcinoma compared with invasive ductal carcinoma in breast: A meta-analysis of PSM studies.

Breast (Edinburgh, Scotland), 51:11-20 pii:S0960-9776(20)30056-4 [Epub ahead of print].

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a rare histological subtype of breast cancer. The outcome of IMPC remains controversial; we conducted a meta-analysis of propensity score matching (PSM) studies to evaluate the prognostic difference between IMPC and invasive ductal carcinoma (IDC).

METHODS: We searched PubMed, EMBASE and the Cochrane library for PSM studies comparing survival data between IMPC and IDC. The summarized odds ratios (ORs) and 95% confidence interval (95% CI) are calculated by STATA software utilizing fixed-effect or random-effect models, depending on the heterogeneity of the eligible studies.

RESULTS: Eight PSM studies including 2102 IMPC patients are included in the meta-analysis. Compared with IDC, IMPC has a similar overall survival (OS) (estimated OR = 0.87, 95% CI: 0.61-1.25), but a shorter relapse free survival (RFS) (estimated OR = 1.31, 95% CI: 1.06-1.61); the shorter RFS might owe to the significantly higher loco-regional recurrence rate of IMPC (estimated OR = 3.60, 95% CI: 1.99-6.52). Funnel plots and Egger's tests are used to evaluate publication bias and the p value for OS and RFS are 0.036 and 0.564 respectively.

CONCLUSIONS: Our results demonstrate that compared with IDC, IMPC exhibits a similar, even favorite OS, but a shorter RFS; and the shorter RFS might owe to the significantly higher loco-regional recurrence rate of IMPC. These results could contribute to the individualized therapy and follow-up strategies for IMPC patients.

RevDate: 2020-03-13

Dixon J, Jasra B, Ankola A, et al (2020)

Bracketed Radioactive Seed Localization for Breast Conservation Surgery.

The American surgeon, 86(2):90-94.

We aimed to evaluate the surgical margin outcomes and re-excision rates in patients undergoing bracketed seed localization of biopsy-proven breast cancer detected on screening mammogram. After approval by our Institutional Review Board, we retrospectively identified patients who had undergone iodine-125 seed localized lumpectomy at our institution from January 2010 to June 2017 by one of two fellowship-trained breast surgeons. Of those patients, a subset of 25 patients were identified who had undergone bracketed seed localization, defined as two or more seeds used to delineate the radiographic borders of the area of concern. All patients had originally presented with calcifications identified on screening mammogram that were subsequently diagnosed as ductal carcinoma in situ and/or invasive ductal carcinoma by image-guided biopsy performed at our institution. Eight patients had one positive margin on final surgical pathology and required re-excision (32%). One patient was converted to mastectomy. Of the patients requiring re-excision, the average maximum linear extent of calcifications was 3.4 cm (SD 0.97), whereas it was 3.1 cm (SD 1.2) in patients with negative surgical margins (P = 0.5). Bracketing calcifications with radioactive seeds can potentially allow more patients to undergo breast conservation surgery.

RevDate: 2020-03-12

Guo T, Chen Z, Xu J, et al (2020)

Change of Pathological Type to Metaplastic Squamous Cell Carcinoma of the Breast During Disease Recurrence: Case Report and Literature Review.

Frontiers in oncology, 10:32.

Background: Metaplastic squamous cell carcinoma (SCC) of the breast is a rare and heterogeneous group of primary breast malignancies. The etiology, pathogenesis, and proper treatment for this kind rare breast cancer are still unclear. Case presentation: We reported a case of a 55-year-old woman with a palpable lump in the inner quadrant of the right breast. She underwent a right breast mass resection and sentinel lymph node biopsy, which revealed that the tumor was an invasive ductal carcinoma, followed by four cycles of doxorubicin plus cyclophosphamide and four cycles of docetaxel as adjuvant chemotherapy, and then simultaneous integrated boost intensity modulated radiotherapy to the whole right breast. After 2 years' follow-up, she had biopsy-proven disease recurrence in the right breast, which revealed SCC, and a mammogram showed abnormalities in the lower inner quadrant of the right breast and left axillary lymph nodes. Then we performed bilateral breast modified radical mastectomy, which confirmed that the recurrent tumors were metaplastic SCC, followed by adjuvant chemotherapy and adjuvant radiotherapy of the left supraclavicular and apical axillary regions. There has been no recurrent or metastatic evidence in the 16 months' follow-up since the second surgery. Conclusion: This case report shows that evolution of pathology type in recurrent breast cancer after initial treatment is possible. Detailed pathologic and immunohistochemical analyses are needed for identification of this change. Surgery and adjuvant radiation and chemotherapy are appropriate treatments for recurrent primary SCC of the breast.

RevDate: 2020-03-11

Egawa C, Yanai A, Yanagawa T, et al (2019)

[Long-Term Survival in a Case of Breast Cancer with Brain Metastases and No Other Distant Metastases Treated by Surgical Removal and Gamma Knife Radiosurgery].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2063-2065.

A 44-year-oldwoman was diagnosedwith right breast cancer andund erwent mastectomy andaxillary lymph node dissection in February 2006. She was pathologically diagnosed with invasive ductal carcinoma without lymph node metastasis. Immunohistochemical examination showedthat the tumor was estrogen receptor positive, progesterone receptor negative, andhada HER2 status score of 0. She received 4 cycles of AC, followedby leuprorelin andtamoxifen. Several metastases were identified in the right supraclavicular lymph nodes in August 2008 during the endocrine therapy. Then, she received S-1 as the first-line chemotherapy. Although metastases showed complete response, she developed an eye disorder caused by S-1 and thus the treatment agent was changedto leuprorelin andanastrozole. She complainedof headache andright homonymous hemianopsia in November 2013. MRI showeda 42mm diameter tumor in the left occipital lobe, suspectedto be brain metastasis from breast cancer. Craniotomy was performedto remove the brain tumor, which was pathologically diagnosedas metastasis from breast cancer. In the brain tumor, the estrogen receptor status hadchangedto negative, but the HER2 status remained unchanged, showing a score of 0. Vinorelbine was administered after the brain surgery. Unfortunately, brain metastasis was foundin the dura mater near the surgical cavity, andgamma knife radiosurgery was performedin January 2014. Thereafter, brain metastases were repeatedly found, and gamma knife radiosurgery was again performed in January 2015, September 2016, and February 2017. In addition, a large tumor appearedin the left occipital lobe andwas surgically removed in June 2016. No other distant metastases were found, andvinorelbine was continueduntil February 2018. Because the patient developed dyslexia caused by gamma knife-induced radiation necrosis, bevacizumab was administered between November 2018 and April 2019. MRI showed that the edema due to radiation necrosis reduced and dyslexia symptoms improved. As of now, she has survivedfor 5 years and 6 months after the diagnosis of brain metastases.

RevDate: 2020-03-11

Miyoshi T, Yamaguchi S, Shiobara M, et al (2019)

[A New Projection-Marking Technique for Breast-Conserving Surgery Using a Radiation Treatment Planning System and Multi-Leaf Collimator in Patients with Breast Cancer-A Pilot Study].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):1922-1924.

In this study, a breast-conserving surgery(BCS)was performed involving the new image projection technique, using a radiation treatment planning system(RTPS)and a multi-leaf collimator(MLC), for patients with ductal carcinoma in situ (DCIS)and invasive ductal carcinoma(IDC)with ductal components. This study aimed to evaluate the feasibility of this procedure as a pilot study. From June 2014 to May 2017, 27 patients diagnosed with DCIS and IDC with ductal components underwent BCS. In the RTPS, the design of tumor resection was simulated, and the extent of resection was projected to the breast surface using the MLC. BCS was performed using this skin marking. Among 27 patients, 4(14.8%)had carcinoma in the surgical margins. As a pilot study, the simplicity and usefulness of this procedure was confirmed in BCS for patients with DCIS and IDC with ductal components. Further evaluation of its safety and efficacy will be conducted in more patients.

RevDate: 2020-03-11

Kinoshita H, Teraoka H, Mori T, et al (2019)

[A Case of Breast Cancer Liver Metastases with Jaundice Responding to Chemotherapy].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2461-2463.

A 50-year-old woman was referred to our hospital due to breast cancer with multiple liver metastasis diagnosed by CT scan. Laboratory findings showed liver dysfunction(T-Bil 7.6mg/dL)with marked elevation of tumor markers(CEA 727.9 ng/mL). Breast tumor biopsy showed an invasive ductal carcinoma(scirrhous type), ER(+), PgR(-), and HER2(3+). Combination therapy with docetaxel, carboplatin and, trastuzumab was administered after the end of 1 course of weekly paclitaxel plus bevacizumab regimen. The patient maintained a good condition without liver dysfunction 8 months after the first visit. Follow-up CT scan showed partial response of breast and hepatic tumors. Our case suggests that careful chemotherapy can improve the prognosis of breast cancer with liver metastasis even if a patient is in an icteric condition.

RevDate: 2020-03-11

Morisaki T, Takashima T, Asano Y, et al (2019)

[Two Cases of Orbital Metastasis from Breast Cancer].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2392-2394.

Orbital metastasis from breast cancer is a rare condition. Here, we describe 2 cases of orbital metastasis from breast cancer. The first patient was a 26-year-old woman diagnosed with triple-negative invasive ductal carcinoma. She underwent surgery after neoadjuvant chemotherapy. One year after surgery, she had multiple bone metastases and then multiple liver metastases developed. During chemotherapy for metastatic disease, she complained ofheadaches and visual disturbances. Findings ofa MRI scan suggested a metastatic tumor in the left orbit. A total of 30 Gy of radiation therapy was administered, but she died a month after the orbital metastasis was discovered. The second patient was a 42-year-old woman, who had advanced breast cancer with bone metastasis. Diplopia developed 8 months after initiation of chemotherapy. Meningeal dissemination was suspected because ophthalmological examination revealed swelling ofbilateral optic discs. She lost her sight within a month. She died 2 months after the diagnosis oforbital metastasis. There was no evidence ofcentral nervous system metastasis in either case. Loss ofvision severely impairs patients' quality oflif e. It is important to know that there is rarely such a rapid progression ofdisease, especially in young patients with triple-negative disease.

RevDate: 2020-03-11

Asano Y, Kashiwagi S, Kouhashi R, et al (2019)

[A Case of Advanced Breast Cancer with Altered Biology by Eribulin Chemotherapy].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2330-2332.

In the treatment of advanced breast cancer, onlya few drugs confer overall survival(OS)benefit. Eribulin is a drug that was shown to extend OS in an international phase Ⅲtrial; however, the underlying mechanism is thought to involve cancer microenvironment regulation. The concept of "breast cancer subtype discordance" implies the biological changes that accompany treatment. Herein, we encountered a case of advanced breast cancer in a 54-year-old woman that showed biological changes after eribulin chemotherapy. The patient noticed a lump in her left breast and visited a nearby doctor, who referred her to our hospital for close examination and treatment. Ultrasonographyrevealed a large mass at the center of the left mammarygland and axillaryly mph node swelling. Core-needle biopsyconfirmed an invasive ductal carcinoma(ER stronglypositive, PgRnegative, HER-2 negative, Ki-67 low expression). CT findings showed multiple lung metastases. Letrozole was administered for cT4N2M1, stage Ⅳ, Luminal A, which showed progression to the left side with advances in breast cancer. Six months later, the primarytumor and axillaryly mph nodes showed progression. Subsequent treatment with eribulin was started, and partial response was obtained; however, new lymph node metastasis developed in the axilla after 11 cycles. The primary tumor and axillaryly mph nodes showed stronglypositive ER expression, were PgR-negative and HER2-positive, and showed Ki-67 low expression and HER2-positive conversion.

RevDate: 2020-03-11

Sannomiya H, Okamoto T, Ryu S, et al (2019)

[A Case of Small Cell Carcinoma of the Pancreas].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2312-2314.

A 55-year-old man was admitted to our hospital for jaundice. Magnetic resonance cholangiopancreatography showed a mass in the pancreatic head as well as biliary obstruction. We strongly suspected invasive ductal carcinoma of the pancreas. We performed pancreaticoduodenectomy with partial resection of the portal vein. The histopathological diagnosis was small cell carcinoma of the pancreas. We detected metastasis of the right hilar lymph node in PET-CT scan performed 2 months after the surgery and started chemotherapy with cisplatin(CDDP)plus irinotecan(CPT-11). However, we observed recurrent metastasis of the right hilar lymph node 12 months after the surgery. We started second-line chemotherapy with amrubicin(AMR)and radiotherapy. Unfortunately, the patient died from multiple metastases of the left adrenal gland and brain 26 months after the surgery. The prognosis of small cell carcinoma of the pancreas is extremely poor. Multimodal treatment such as chemotherapy, radiotherapy, and curative operation are required for long-term survival.

RevDate: 2020-03-11

Nakama Y, Maruyama Y, Hisaka T, et al (2019)

[A Vesected Case of Pancreatic Metastasis from Breast Cancer Which Recurred Six Years after Breast Surgery].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2309-2311.

A 43-year-old woman who underwent surgical resection of invasive ductal carcinoma in the left breast at the age of 37 years old presented at our hospital for evaluation of pancreatic tumor. The original tumor was estrogen receptor(ER)progesterone receptor(PgR)and HER2 positive. At that time, she underwent radical mastectomy with no evident nodal disease. Postoperatively, the patient was placed on adjuvant tamoxifen therapy for several years. Six years following the original diagnosis of breast cancer, she was referred to the hospital for routine check-up while asymptomatic. Follow-up examination showed a solitary hypodense mass approximately 0.9 cm in size in the pancreas body on dynamic CT scan. The patient underwent a standard distal pancreatectomy with standard regional lymphadenectomy. Histopathological examination and immunohistochemical features revealed that the tumor was compatible with metastatic pancreatic adenocarcinoma from breast cancer.

RevDate: 2020-03-11

Sugimoto H, Miura T, Kawamura Y, et al (2019)

[Case Report of Long-Term Clinical Efficacy of Paclitaxel plus Bevacizumab Combination Therapy for Stage Ⅳ AdvancedBreast Cancer].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2246-2248.

A 50-year-old woman had noted a mass in her right breast 2 years ago but did not consult a hospital. She consulted our hospital because the mass increased in size and also reddened. The tumor measured 10 cm in diameter and was palpable in the whole right breast. A core needle biopsy was performed, and invasive ductal carcinoma was diagnosed. CT showed multiple lung and liver metastases and bone scintigraphy showed bone metastases in a rib. Because the lung and liver metastases were life-threatening, paclitaxel(PTX)chemotherapy was administered weekly. Biomarkers analysis revealed ER(+), PgR(+), HER2(2+), HER2 FISH 1.27, Ki-67 30%, and bevacizumab (Bev) was added from 2 courses. After 4 courses of chemotherapy, the multiple lung and liver metastases were found to be significantly reduced on CT. Toxicities included alopecia, hypertension, and proteinuria. At this time, 3 years after the treatment started, PTX plus Bev combination therapy was also administered.

RevDate: 2020-03-11

Fushimi K, Kusashio K, Yasutomi J, et al (2019)

[Adenosquamous Carcinoma in the Remnant Pancreas after Pancreatoduodenectomy for Invasive Pancreas Cancer-A Resected Case with Five-Year Relapse-Free Survival].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2198-2200.

A 52-year-old man underwent pancreatoduodenectomy(PD)for invasive cancer of the pancreatic head, with a histopathological diagnosis of moderately to poorly differentiated invasive ductal carcinoma. One year and 2 months after PD, follow- up CT revealed a mass 3 cm in diameter in the remnant pancreas without distant metastasis. Therefore, total remnant pancreatectomy was performed with a histopathological diagnosis of adenosquamous carcinoma. Five years after re-excision, the patient remains alive without recurrence. Although no tumor component was found at the anastomotic site of the pancreatojejunostomy, squamous metaplasia with chronic inflammation with carcinogenic potential was diffusely observed in the main pancreatic duct. Clinical cases of remnant pancreatic resection after PD for invasive cancer are relatively rare. Furthermore, this case of adenosquamous carcinoma with long-term recurrence-free survival is extremely rare.

RevDate: 2020-03-11

Sakakibara J, Okubo Y, Tanabe N, et al (2019)

[Differences in Treatment Effect between Local and Distant Lesions in Breast Cancer Patients Administered Neoadjuvant Endocrine TherapyGuided byOncoty pe DX-A Case Report].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2170-2172.

We report different treatment effects between local and distant lesions based on oncotype DX in a patient with breast cancer administered neoadjuvant endocrine therapy. The patient was a 50-year-old woman. Ultrasound(US)showed a mass 16×11×11mm in diameter in the C area of her right breast. Histological examination revealed invasive ductal carcinoma positive for estrogen and progesterone receptor and negative for human epidermal growth factor receptor type 2(HER2), and a Ki-67 index of 38%. The recurrence score(RS)calculated from the core needle biopsy was 4(low-risk group)with a predicted 10-year risk of distant recurrence of 4% after 5 years of endocrine therapy. Oncotype DX showed that this patient would not benefit from chemotherapy. We administered neoadjuvant endocrine therapy. However, the tumor size increased to 26×18×15mm 1 month after treatment initiation. Therefore, right breast-conserving surgery and sentinel lymph node biopsy were performed. Histopathologically, the effect of the endocrine therapy was grade 0 and the surgical margins were negative. Even though RS was low in the breast, the effect of endocrine therapy differed between local and distant lesions such as circulating tumor cells.

RevDate: 2020-03-11

Adachi M, Sasaki M, Ogawa N, et al (2019)

[A Case of Locally Advanced Breast Cancer Successfully Treated with Epirubicin/Cyclophosphamide].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(13):2152-2154.

A 66-year-old woman was referred to our hospital with the chief complaint of a huge exposed left breast mass with bleeding. Triple-negative invasive ductal carcinoma of the breast was diagnosed by core needle biopsy. Computed tomogra- phy showed axillary and infraclavicular lymph node metastases. Epirubicin/cyclophosphamide(EC)therapy was started. We reduced the dose to 80%during courses 2-4. After 4 courses of treatment, CT showed a complete response. We reduced the dose to 50% during courses 5-12 and stopped chemotherapy. Five years have passed without recurrence since the first treatment.

RevDate: 2020-03-11

Salvatorelli L, Puzzo L, Vecchio GM, et al (2020)

Ductal Carcinoma In Situ of the Breast: An Update with Emphasis on Radiological and Morphological Features as Predictive Prognostic Factors.

Cancers, 12(3): pii:cancers12030609.

Ductal carcinoma in situ (DCIS) shows overlapping epidemiology with invasive ductal carcinoma of the breast, sharing similar risk factorssuch as age, mammographic density, family history, and hormonal therapy as well as genetic factors such as BRCA1/BRCA2, histotypes, and molecular subtypes such as luminal A and B, HER2 enriched, and basal-type, thus suggesting its potential precursor role. A small percentage of patients with a history of DCIS die without a documented intermediate diagnosis of invasive breast carcinoma (IBC). The increased risk of death is usually associated with ipsilateral recurrence such as IBC. The slightly variable incidence of DCIS in different countries is mainly due to a different diffusion of mammographic screening and variability of the risk factors. The majority of DCIS lesions are not palpable lesions, which can be only radiologically detected because of the association with microcalcifications. Mammography is a highly sensitive diagnostic procedure for detecting DCIS with microcalcifications, while magnetic resonance imaging (MRI) is considered more sensitive to detect DCIS without calcifications and/or multifocal lesions. The aim of the present overview was to focus on the clinical, radiological, and pathological features of DCIS of the breast, with an emphasis on the practical diagnostic approach, predictive prognostic factors, and therapeutic options.

RevDate: 2020-03-10

Li Z, Fan M, Zhong Z, et al (2020)

Coupling Effect of Molecular Chain Displacement and Carrier Trap Characteristics on DC Breakdown of HDPE/LDPE Blend Insulation.

Polymers, 12(3): pii:polym12030589.

This work focuses on the coupling effect of molecular chain displacement and trap characteristics on direct current (DC) breakdown properties of high density/low density polyethylene (HDPE/LDPE) blend insulation. Frequency domain spectroscopy (FDS) and isothermal discharge current (IDC) are used to characterize the dielectric relaxation and trap characteristics of HDPE/LDPE blends. A DC breakdown model is proposed to reveal the mechanisms of the molecular chain displacement and carrier trap on the DC breakdown strength. The dielectric relaxation α and δ present segmental motions and thermal ion polarization behaviours of HDPE/LDPE blends, respectively. α dielectric relaxation strength (Δεα) increases as the amount of HDPE increases from 0 to 5 wt%, and then declines with a further increase of HDPE content to 20 wt%. According to the velocity equation, the increase of Δεα will increase the molecular chain displacement, resulting in a larger free volume, which will provide electrons with larger free path λ to form hot electrons. A positive correlation exists between the activation energy of the dielectric relaxation process δ and trap density, and the increase of δ dielectric relaxation strength (Δεδ) will adversely affect the breakdown strength of the specimen. HDPE/LDPE blends with 15 wt% HDPE content have lower Δεα and lowest Δεδ, which decreases the mean free path λ of molecular chain and thermal ion polarization. At the same time, it has the highest deep trap density, thus increasing the probability of hot electrons being captured and improving the DC breakdown strength. It is concluded the breakdown of the dielectric is synergistically affected by the molecular chain displacement and carrier trap.

RevDate: 2020-03-09

Karanis M, Koksal H, Ates E, et al (2019)

Clinical importance of fibulin-5 immunohistochemical staining in breast lesions.

Polish journal of pathology : official journal of the Polish Society of Pathologists, 70(4):259-263.

The aim of this study was to evaluate the clinical importance of fibulin-5, which has been shown to display tumour-promoting and tumour-protective functions in breast lesions. Sixty-two breast cancer patients, 19 patients with fibroadenoma, and 15 healthy breast tissues were enrolled. Forty-seven patients had invasive ductal carcinoma (IDC) (12 of them also had in situ carcinoma DCIS), and 15 had invasive lobular carcinoma (ILC). A scoring system from 0 to 4 was used to evaluate the fibulin-5 staining according to the percentage of stained cells. The median values of fibulin-5 staining scores of the breast cancer, fibroadenoma, and healthy breast tissues were 2 (range: 0-4), 3 (range: 3-4), and 4 (range: 1-4), respectively, and the difference is statistically significant (p = 0.0001). There was no significant difference between the fibulin-5 scores of IDC, ILC, and DCIS. Fifteen patients with triple-negative breast cancer (TNBC) had the lowest fibulin-5 score (p < 0.0001). The median fibulin-5 scores of the patients according to Ki-67 index ≥ 14% and < 14% were 2 (range: 1-5) and 4 (range: 1-5), respectively, and the difference is statistically significant (p = 0.001). These data can be explained by the inhibitory effect of fibulin-5 on epithelial cell proliferation, which is closely related to differentiation and prognosis.

RevDate: 2020-03-09

Bernsen MLE, van der Zant FM, Wondergem M, et al (2020)

Incidental Breast Carcinoma Detected With 13N-NH3 Cardiac PET Imaging.

Clinical nuclear medicine [Epub ahead of print].

A 78-year-old woman with chest pain and a history of pacemaker implantation for arrhythmia underwent myocardial perfusion imaging by means of N-NH3 cardiac PET/CT. N-NH3 cardiac PET showed no signs of ischemia or infarction. Incidentally, a nodule with increased N-NH3 activity was observed in the right breast. Histopathologic examination revealed invasive ductal carcinoma.

RevDate: 2020-03-09

Hoffman A, Ben Ishay O, Horesh N, et al (2020)

Breast Cancer in Men: A Single Center Experience Over a Period of 22 years.

The Israel Medical Association journal : IMAJ, 22(3):160-163.

BACKGROUND: Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women.

OBJECTIVES: To review the experience with MBC of a single center in Israel over a period of 22 years.

METHODS: This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993-2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes.

RESULTS: The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A-2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2-178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival.

CONCLUSIONS: MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.

RevDate: 2020-03-09

Mori N, Mugikura S, Miyashita M, et al (2020)

Turbo Spin-echo Diffusion-weighted Imaging Compared with Single-shot Echo-planar Diffusion-weighted Imaging: Image Quality and Diagnostic Performance When Differentiating between Ductal Carcinoma in situ and Invasive Ductal Carcinoma.

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine [Epub ahead of print].

PURPOSE: To compare the image quality between turbo spin-echo (TSE)-diffusion weighted imaging (DWI) and single-shot echo-planar imaging (EPI)-DWI, and to verify the diagnostic performance of the apparent diffusion coefficient (ADC) parameters of the two techniques by using histogram analysis in terms of differentiation between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions.

METHODS: Ninety-four women with 94 lesions diagnosed as breast cancer by surgery underwent IRB-approved preoperative magnetic resonance imaging, including TSE and EPI-DWI with b-values of 50 and 850 s/mm2. Twenty lesions were identified as DCIS and 74 as IDC. Image quality [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and geometric distortion] was evaluated quantitatively and compared between the TSE and EPI-DWI. A histogram analysis of the entire tumor voxel-based ADC data was performed, and the 10th, 25th, 50th, 75th, and 90th percentile values of each technique were compared between DCIS and IDC lesions.

RESULTS: The SNR and CNR of TSE-DWI were significantly higher than those of EPI-DWI (P < 0.0001 and < 0.0001). The geometric distortion of TSE-DWI was significantly lower than that of EPI-DWI (P < 0.0001). In TSE-DWI, the 10th, 25th, 50th, and 75th percentile values were significantly different between the DCIS and IDC lesions (P = 0.0010, 0.0004, 0.0008, and 0.0044, respectively). In EPI-DWI, the 50th and 75th percentile values were significantly different between the two groups (P = 0.0009 and 0.0093). There was no significant difference in the area under the curve of the receiver operating characteristic analysis of the 10th, 25th, 50th, and 75th percentile values of TSE-DWI, and the 50th and 75th percentile values of EPI-DWI (P = 0.29).

CONCLUSION: The image quality of TSE-DWI was better than that of EPI-DWI. DCIS lesions were distinguished from IDC lesions with a wider range of percentile values in TSE-DWI than in EPI-DWI, although diagnostic performance was not significantly different between the techniques.

RevDate: 2020-03-06

Urbaniak A, Jousheghany F, Piña-Oviedo S, et al (2020)

Carbamate derivatives of colchicine show potent activity towards primary acute lymphoblastic leukemia and primary breast cancer cells-in vitro and ex vivo study.

Journal of biochemical and molecular toxicology [Epub ahead of print].

Colchicine (COL) shows strong anticancer activity but due to its toxicity towards normal cells its wider application is limited. To address this issue, a library of 17 novel COL derivatives, namely N-carbamates of N-deacetyl-4-(bromo/chloro/iodo)thiocolchicine, has been tested against two types of primary cancer cells. These included acute lymphoblastic leukemia (ALL) and human breast cancer (BC) derived from two different tumor subtypes, ER+ invasive ductal carcinoma grade III (IDCG3) and metastatic carcinoma (MC). Four novel COL derivatives showed higher anti-proliferative activity than COL (IC50 = 8.6 nM) towards primary ALL cells in cell viability assays (IC50 range of 1.1-6.4 nM), and several were more potent towards primary IDCG3 (IC50 range of 0.1 to 10.3 nM) or MC (IC50 range of 2.3-9.1 nM) compared to COL (IC50 of 11.1 and 11.7 nM, respectively). In addition, several derivatives were selectively active toward primary breast cancer cells compared to normal breast epithelial cells. The most promising derivatives were subsequently tested against the NCI panel of 60 human cancer cell lines and seven derivatives were more potent than COL against leukemia, non-small-cell lung, colon, CNS and prostate cancers. Finally, COL and two of the most active derivatives were shown to be effective in killing BC cells when tested ex vivo using fresh human breast tumor explants. The present findings indicate that the select COL derivatives constitute promising lead compounds targeting specific types of cancer.

RevDate: 2020-03-06

Choi JE, Hyun CL, Jin MS, et al (2020)

Downregulation of N-myc and STAT Interactor Protein Predicts Aggressive Tumor Behavior and Poor Prognosis in Invasive Ductal Carcinoma.

Journal of breast cancer, 23(1):36-46.

Purpose: We investigated the expression of the N-myc and STAT interactor (NMI) protein in invasive ductal carcinoma tissue and estimated its clinicopathologic significance as a prognostic factor. The expression levels and prognostic significance of NMI were also analyzed according to the molecular subgroup of breast cancers.

Methods: Human NMI detection by immunohistochemistry was performed using tissue microarrays of 382 invasive ductal carcinomas. The correlation of NMI expression with patient clinicopathological parameters and prognostic significance was analyzed and further assessed according to the molecular subgroup of breast cancers. Moreover, in vitro experiments with 13 breast cancer cell lines were carried out. We also validated NMI expression significance in The Cancer Genome Atlas cohort using the Human Protein Atlas (HPA) database.

Results: Low NMI expression was observed in 190 cases (49.7%). Low NMI expression was significantly associated with the "triple-negative" molecular subtype (p < 0.001), high nuclear grade (p < 0.001), high histologic grade (p < 0.001), and advanced anatomic stage (p = 0.041). Patients with low NMI expression had poorer progression-free survival (p = 0.038) than patients with high NMI expression. Low NMI expression was not significantly associated with patient prognosis in the molecular subgroup analysis. In vitro, a reduction of NMI expression was observed in 8 breast cancer cell lines, especially in the estrogen receptor-positive and basal B type of triple-negative breast cancer molecular subgroups. The HPA database showed that low NMI expression levels were associated with a lower survival probability compared with that associated with high NMI expression (p = 0.053).

Conclusion: NMI expression could be a useful prognostic biomarker and a potential novel therapeutic target in invasive ductal carcinoma.

RevDate: 2020-03-06

Roy S, Kumar R, Mittal V, et al (2020)

Classification models for Invasive Ductal Carcinoma Progression, based on gene expression data-trained supervised machine learning.

Scientific reports, 10(1):4113 pii:10.1038/s41598-020-60740-w.

Early detection of breast cancer and its correct stage determination are important for prognosis and rendering appropriate personalized clinical treatment to breast cancer patients. However, despite considerable efforts and progress, there is a need to identify the specific genomic factors responsible for, or accompanying Invasive Ductal Carcinoma (IDC) progression stages, which can aid the determination of the correct cancer stages. We have developed two-class machine-learning classification models to differentiate the early and late stages of IDC. The prediction models are trained with RNA-seq gene expression profiles representing different IDC stages of 610 patients, obtained from The Cancer Genome Atlas (TCGA). Different supervised learning algorithms were trained and evaluated with an enriched model learning, facilitated by different feature selection methods. We also developed a machine-learning classifier trained on the same datasets with training sets reduced data corresponding to IDC driver genes. Based on these two classifiers, we have developed a web-server Duct-BRCA-CSP to predict early stage from late stages of IDC based on input RNA-seq gene expression profiles. The analysis conducted by us also enables deeper insights into the stage-dependent molecular events accompanying IDC progression. The server is publicly available at http://bioinfo.icgeb.res.in/duct-BRCA-CSP.

RevDate: 2020-03-06

Sun T, Yang W, Toprani SM, et al (2020)

Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram.

Cell communication and signaling : CCS, 18(1):36 pii:10.1186/s12964-019-0507-3.

BACKGROUND: The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response.

METHODS: High aldehyde dehydrogenase activity (ALDH)bright and CD44+/CD24-/ESA+ cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA).

RESULTS: We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors.

CONCLUSION: DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.

RevDate: 2020-03-05

Lawrence MG, Porter LH, Clouston D, et al (2020)

Knowing what's growing: Why ductal and intraductal prostate cancer matter.

Science translational medicine, 12(533):.

Prostate cancer is a common malignancy, but only some tumors are lethal. Accurately identifying these tumors will improve clinical practice and instruct research. Aggressive cancers often have distinctive pathologies, including intraductal carcinoma of the prostate (IDC-P) and ductal adenocarcinoma. Here, we review the importance of these pathologies because they are often overlooked, especially in genomics and preclinical testing. Pathology, genomics, and patient-derived models show that IDC-P and ductal adenocarcinoma accompany multiple markers of poor prognosis. Consequently, "knowing what is growing" will help translate preclinical research to pinpoint and treat high-risk prostate cancer in the clinic.

RevDate: 2020-03-02

Rangel GW, Clark MA, Kanjee U, et al (2020)

Plasmodium vivax transcriptional profiling of low input cryopreserved isolates through the intraerythrocytic development cycle.

PLoS neglected tropical diseases, 14(3):e0008104 pii:PNTD-D-19-00667 [Epub ahead of print].

Approximately one-third of the global population is at risk of Plasmodium vivax infection, and an estimated 7.51 million cases were reported in 2017. Although, P. vivax research is currently limited by the lack of a robust continuous in vitro culture system for this parasite, recent work optimizing short-term ex vivo culture of P. vivax from cryopreserved isolates has facilitated quantitative assays on synchronous parasites. Pairing this improved culture system with low-input Smart-seq2 RNAseq library preparation, we sought to determine whether transcriptional profiling of P. vivax would provide insight into the differential survival of parasites in different culture media. To this end we probed the transcriptional signature of three different ex vivo P. vivax samples in four different culture media using only 1000 cells for each time point taken during the course of the intraerythrocytic development cycle (IDC). Using this strategy, we achieved similar quality transcriptional data to previously reported P. vivax transcriptomes. We found little effect with varying culture media on parasite transcriptional signatures, identified many novel gametocyte-specific genes from transcriptomes of FACS-isolated gametocytes, and determined invasion ligand expression in schizonts in biological isolates and across the IDC. In total, these data demonstrate the feasibility and utility of P. vivax RNAseq-based transcriptomic studies using minimal biomass input to maximize experimental capacity.

RevDate: 2020-03-02

Ruiz-Esparza-Garrido R, Torres-López J, Piña-Sánchez P, et al (2020)

Expression changes of BIK in breast cancer tissues of different histological subtypes.

Cirugia y cirujanos, 88(2):163-169.

Objective: The objective of the study was to determine the expression levels of BIK in breast cancer (BC) tissues of different histological subtype and to delve into the participation of BIK in this type of cancer.

Materials and methods: BIK and p-BIK (the phosphorylated form) protein expressions were tested by immunohistochemistry in BC tissue microarrays (Tumoral [n = 90] and adjacent [n = 40] tissues).

Results: The data revealed an overexpression of BIK in invasive ductal (Grades I, IIA, and IIB) and in lobular (Grades IIA and IIB) carcinomas compared to their respective adjacent tissues. By contrast, canalicular carcinoma (Grades I and IIB) and phyllodes tumors had very low expression levels of BIK. Only levels of p-BIK were shown to be increased in invasive ductal carcinoma (Grades I, IIA, and IIB). Meanwhile, quantitative polymerase chain reaction analysis showed lower BIK levels in MCF-10A and MCF-7 cells than in MDA-MB-231 and human mammary epithelial cells. In agreement with this, BIK protein was shown to be overexpressed in MDA-MB 231 relative to MCF-7 cells.

Conclusions: Our results showed an association between BIK expression and the BC tumor subtype under study, which could be related to different BIK functions in the BC subtypes.

RevDate: 2020-03-02

Veverkova L, Melichar B, Zlamalova N, et al (2020)

Association between negative preoperative axillary node staging and surgical sentinel node biopsy in patients with newly diagnosed breast cancer: A retrospective analysis.

Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia [Epub ahead of print].

AIM: The aim of this retrospective study was to analyse the preoperative ultrasound findings in patients with minimal or almost no morphological changes of axillary lymph nodes (LN) and to correlate these findings with the results of sentinel node (SN) biopsy.

MATERIALS AND METHODS: Between January 2014 and September 2018, 289 female patients with newly diagnosed breast cancer and negative preoperative axillary staging were examined with preoperative ultrasound evaluation of axillary LNs. Patients with no evidence of LN metastases underwent primary surgical treatment with SN biopsy. Negative predictive value (NPV) of preoperative ultrasound was evaluated and the histopathological findings in positive SN biopsies were correlated with tumour type and preoperative ultrasound LN imaging.

RESULTS: Of 289 patients with negative preoperative axillary staging who had primary surgical treatment, 268 patients had negative SN biopsy while SN metastases were detected in 21 patients. Of patients with positive SN biopsies, 2 patients had negative core biopsy of axillary LN before surgery. The preoperative ultrasound examination was negative in the remaining 19 patients with SN metastases.

CONCLUSIONS: Preoperative ultrasonography is very accurate in the detecting of axillary LN metastases. Patients with primary tumour size ≥ 1 cm, with grade ≥ 2 no special type carcinomas (NST - no special type, also known as invasive ductal carcinoma) or multicentric lobular invasive cancer should undergo a more thorough ultrasound evaluation.

RevDate: 2020-02-28

Monfared SS, Lebeau JC, Mason J, et al (2020)

A Bio-Physio-Psychological Investigation of Athletes' Burnout.

Research quarterly for exercise and sport [Epub ahead of print].

Purpose: Changes in biophysiological markers related to perceived burnout and self-comfort were tested in this study. Method: Forty-two student-athletes from middle and high school grades were evaluated for burnout, salivary cortisol levels, measures of arousal-related physiological markers (i.e., blood volume pulse; BVP), galvanic skin response (GSR), and respiratory rate, and self-comfort variables during the last two weeks of the season. Using self-comfort theory as its conceptual framework, we examined burnout through a conceptual model in which feeling of discomfort with the self was related to biophysiological markers affecting perceived burnout. The proposed model was tested by using a partial least squares structural equation modeling (PLS-SEM). Results: The main findings indicate that increased self-discomfort is significantly (p < .001) associated with increased salivary cortisol (β = - 0.189) along with a significant (p = .050) decrease in GSR (β = - 0.259). Increased salivary cortisol is significantly (p < .001) associated with increased burnout (β = 0.242). Conclusion: The findings partially support the model and encourage further effort to capture the burnout syndrome through the integration of biological and psychological markers.

RevDate: 2020-02-28

Kumarguru BN, Ramaswamy AS, Shaik S, et al (2020)

Tumor budding in invasive breast cancer - An indispensable budding touchstone.

Indian journal of pathology & microbiology, 63(Supplement):S117-S122.

Background: Tumor budding denotes a phenomenon in which the tumor cells, singly or in small aggregates, become detached from the neoplastic glands at the invasive front of adenocarcinoma. Tumors with budding cells have a significantly more aggressive clinical course. Significance of tumor budding has mainly been examined in the field of colorectal cancer.

Aims: To document the number tumor buds at the invasive front of invasive breast cancer. To correlate the number of tumor buds with other histopathological parameters, and available clinical details.

Setting and Study Design: Analytical study at a rural tertiary care referral institute.

Materials and Methods: It was a retrospective study of invasive breast cancer cases from January 2012 to April 2015. Tumor buds were counted in H and E stained sections in 10 High Power Fields (HPFs). Association of tumor budding with histological parameters and available clinical details were analyzed statistically.

Statistical Analysis Used: Frequencies, Chi-Square Test and Crosstabs were used for calculation.

Results: 50 cases of invasive breast carcinoma were analyzed. Invasive ductal carcinoma constituted predominant histological type (92%). Low tumor budding (tumor buds ≤20/10HPFs) constituted 20 cases. High tumor budding (tumor buds >20/10HPFs) constituted 30 cases. Association of high tumor budding with lympho-vascular invasion, lymph node metastasis, primary tumor staging, regional lymph node staging, necrosis and Monckeberg medial sclerosis was statistically significant.

Conclusion: Tumor budding may be incorporated as a new parameter in reporting protocols. Tumor budding serves as an indispensable touchstone in evaluating cases of invasive breast cancer.

RevDate: 2020-02-27

Tewari SG, Swift RP, Reifman J, et al (2020)

Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite.

Malaria journal, 19(1):94 pii:10.1186/s12936-020-03174-z.

BACKGROUND: Human blood cells (erythrocytes) serve as hosts for the malaria parasite Plasmodium falciparum during its 48-h intraerythrocytic developmental cycle (IDC). Established in vitro protocols allow for the study of host-parasite interactions during this phase and, in particular, high-resolution metabolomics can provide a window into host-parasite interactions that support parasite development.

METHODS: Uninfected and parasite-infected erythrocyte cultures were maintained at 2% haematocrit for the duration of the IDC, while parasitaemia was maintained at 7% in the infected cultures. The parasite-infected cultures were synchronized to obtain stage-dependent information of parasite development during the IDC. Samples were collected in quadruplicate at six time points from the uninfected and parasite-infected cultures and global metabolomics was used to analyse cell fractions of these cultures.

RESULTS: In uninfected and parasite-infected cultures during the IDC, 501 intracellular metabolites, including 223 lipid metabolites, were successfully quantified. Of these, 19 distinct metabolites were present only in the parasite-infected culture, 10 of which increased to twofold in abundance during the IDC. This work quantified approximately five times the metabolites measured in previous studies of similar research scope, which allowed for more detailed analyses. Enrichment in lipid metabolism pathways exhibited a time-dependent association with different classes of lipids during the IDC. Specifically, enrichment occurred in sphingolipids at the earlier stages, and subsequently in lysophospholipid and phospholipid metabolites at the intermediate and end stages of the IDC, respectively. In addition, there was an accumulation of 18-, 20-, and 22-carbon polyunsaturated fatty acids, which produce eicosanoids and promote gametocytogenesis in infected erythrocyte cultures.

CONCLUSIONS: The current study revealed a number of heretofore unidentified metabolic components of the host-parasite system, which the parasite may exploit in a time-dependent manner to grow over the course of its development in the blood stage. Notably, the analyses identified components, such as precursors of immunomodulatory molecules, stage-dependent lipid dynamics, and metabolites, unique to parasite-infected cultures. These conclusions are reinforced by the metabolic alterations that were characterized during the IDC, which were in close agreement with those known from previous studies of blood-stage infection.

RevDate: 2020-02-27

Nakamura R, Oyama T, Inokuchi M, et al (2020)

The relation between anti-TGBFR1 immunohistochemical reaction and low Ki67, small tumor size and high estrogen receptor expression in invasive breast cancer.

Pathology international [Epub ahead of print].

Most breast cancers are derived from the luminal epithelium, which composes the inside of the breast ductal structure. Ductal carcinoma in situ (DCIS) leads to invasive ductal carcinoma, but noncancerous intraductal proliferative lesions are also a risk factor for ductal carcinoma. The transforming growth factor beta (TGFB) signaling pathway behaves as a tumor suppressor in the early stage of cancer, and conversely as a tumor growth factor in invasive stages in several cancers. In this study, we performed immunohistochemistry with an antibody that detects the cytoplasmic region of TGFB receptor 1 (TGFBR1) and elucidated TGFBR1 protein expression in luminal epithelial cells of noncancerous breast ducts and in several cases of DCIS and invasive carcinoma. TGFBR1 expression was higher in noncancerous breast tissue than in cancerous tissue, and a difference in expression was also seen among histological subtypes. Comparing the expression level of TGFBR1 in cancer cells and clinico-pathological parameters, cases expressing low TGFBR1 tended to show low estrogen receptor expression, large tumor size (≥10 mm), and a high Ki67 labeling index. These data suggested that TGFBR1 protein expression may be related to the suppression of breast cancer cell growth.

RevDate: 2020-02-26

Mohamed KEH, A Elamin (2020)

Adherence to endocrine therapy and its relation to disease-free survival among breast cancer patients visiting an out-patient clinic at Khartoum Oncology Hospital, Sudan.

Journal of evaluation in clinical practice [Epub ahead of print].

RATIONALE: Adherence to endocrine therapy provides substantial reduction in breast cancer (BC) relapses and improve survival. Hence, non-adherence remains an under reported issue mainly in developing countries.

AIMS AND OBJECTIVES: The aim of this study is to evaluate the adherence to endocrine therapy (tamoxifen [TAM] and aromatase inhibitors [AIs]) among BC patients visiting an out-patient clinic (2015-2016) in Khartoum Oncology Hospital, Sudan.

METHODS: Adherence was assessed using pills count and self-reporting methods. A total of 172 patients were interviewed. Also, records were reviewed for demographic and other cancer characteristics.

RESULTS: The patients' mean age at diagnosis was 53 years, with the highest frequency at (41-60) years. Invasive ductal carcinoma 69.2% formed the main pathological diagnosis. T2 tumour size (51.2%) and lymph node involvement (N1) (31.4%) were most evident. Also, the majority of patients were stage III (45.9%) and grade II (48%). The studied women were postmenopausal (49.4%) and premenopausal (47.7%). Regarding hormonal receptors, about 68% were oestrogen (ER)+/progesterone (PR)+ and 23.3% were ER+/PR-. Studying adherence, almost (93%) of the studied group were ≥80% adherent to TAM and AIs. The hormonal therapy persistence mean was 27.2 ± 22.5 months (40-96). While adherence percentage mean was 93.7 ± 13.6% (0%-100%). Also disease-free survival (DFS) mean was 36.3 ± 32.7 months (4-312). Adherence to hormonal therapy and persistence were significantly correlated (P < .000). Also, statistically significant association was found between hormonal therapy adherence (≥80%) and patient poor to average economic status (P = .006), and the marital status "married" (P = .008).

CONCLUSIONS: A high rate of adherence (93%) to endocrine therapy was estimated in the present study. Also, a positive association was found between the hormonal therapy persistence, and the DFS year's groups (P = .000), and the hormonal therapy types (P = .000). Adherence to hormonal therapy and persistence were significantly correlated (P < .000).

RevDate: 2020-02-26

Xu Z, Shen W, Pan A, et al (2020)

Decreased Nek9 expression correlates with aggressive behaviour and predicts unfavourable prognosis in breast cancer.

Pathology pii:S0031-3025(20)30458-X [Epub ahead of print].

As a new member of Neks family, Nek9 regulates spindle assembly and controls chromosome alignment and centrosome separation. In the current study we aimed to investigate the expression of Nek9 in breast cancer and its clinical significance. We evaluated the expression of Nek9 in invasive ductal carcinoma (IDC, n=316), ductal carcinoma in situ (DCIS), usual ductal hyperplasia, atypical ductal hyperplasia, fibroadenoma and normal breast tissues using immunohistochemistry. The results revealed significantly reduced Nek9 in IDCs (41.8%) compared to benign breast lesions. Moreover, gradually reduced Nek9 was found from DCIS to invasive carcinoma and metastatic tumour within the same tumours. The decrease in Nek9 expression was associated with larger tumour size (p=0.0087), high grade (p<0.0001) and high Ki-67 index (p<0.0020). TCGA and GEO datasets analysis revealed low level of Nek9 mRNA was more frequent in triple negative breast cancers, and associated with poor overall survival and distant metastasis-free survival. These findings suggest an important role of Nek9 in the progression of breast cancer, and aberrantly expressed Nek9 correlates with more aggressive clinicopathological variables and predicts poor clinical prognosis. Nek9 may serve as a potential predictive factor for patients with breast cancer.

RevDate: 2020-02-25

Kadivar M, F Aram (2020)

Assessment of Ki67 in Breast Cancer: A Comparison Between the Eye-10 Method, Stepwise Counting Strategy, and International System of Ki67 Evaluation.

Iranian journal of pathology, 15(1):13-18.

Background & Objective: Ki-67 evaluation is an essential tool to define luminal A and B breast cancers, which is not yet systematized. The International Ki67 in Breast Cancer Working Group suggests the counting of 500 or 1000 cancer cells, which is a time-consuming process. Therefore, novel methods, such as the Eye-10 method and stepwise counting strategy, are proposed to facilitate measurement.

Methods: Immunohistochemical staining of Ki67 was performed on 100 hormone-receptor-positive invasive ductal carcinoma specimens. Ki67LI was evaluated for each case, and then results were dichotomized by a cut-off point of 20%. Next, for each sample, an expert pathologist visually assessed percentages of Ki67-positive cells in 10% intervals at a glance (Eye-10 method). Finally, by using a dynamic process with rejection regions, Ki67 was defined so if the estimate belonged to the upper or lower rejection region, the Ki67 status had been determined and if the rejection region could not be reached after counting the maximum number of 400 tumor cells, the specimen was regarded as equivocal (stepwise counting strategy).

Results: The comparison between Eye-10 and Ki67LI revealed almost perfect agreement (kappa coefficient =0.889), and the concordance between the stepwise counting strategy and Ki67LI was substantial (kappa coefficient =0.639).

Conclusion: Both two methods left some results in the gray/intermediate zone, which is unavoidable. Both methods are much faster and simpler than evaluation of Ki67LI and are also reliable. Regarding the gray zone in both methods, further improvements in the methodology, as well as more analytical studies, are needed.

RevDate: 2020-02-24

Long M, Verbeke W, Ein-Dor T, et al (2020)

A functional neuro-anatomical model of human attachment (NAMA): Insights from first- and second-person social neuroscience.

Cortex; a journal devoted to the study of the nervous system and behavior, 126:281-321 pii:S0010-9452(20)30035-6 [Epub ahead of print].

Attachment theory, developed by Mary Ainsworth and John Bowlby about seventy years ago, has become one of the most influential and comprehensive contemporary psychology theories. It predicts that early social interactions with significant others shape the emergence of distinct self- and other-representations, the latter affecting how we initiate and maintain social relationships across the lifespan. A person's attachment history will therefore associate with inter-individual differences in emotional and cognitive mechanisms sustaining representations, modeling, and understanding of others on the biological and brain level. This review aims at summarizing the currently available social neuroscience data in healthy participants on how inter-individual differences in attachment associate with brain anatomy and activity across the lifespan, and to integrate these data into an extended and refined functional neuro-anatomical model of human attachment (NAMA). We first propose a new prototypical initial attachment pathway and its derivatives as a function of attachment security, avoidance, and anxiety. Based on these pathways, we suggest a neural attachment system composed of two emotional mentalization modules (aversion and approach) and two cognitive mentalization modules (emotion regulation and mental state representation) and provide evidence on their functionality depending on inter-individual differences in attachment. We subsequently expand this first-person social neuroscience account by also considering a second-person social neuroscience perspective comprising the concepts of bio-behavioral synchrony and particularly inter-brain coherence. We hope that such extended and refined NAMA can inform attachment theory and ultimately help devising new prevention and intervention strategies for individuals and families at risk for attachment-related psychopathology.

RevDate: 2020-02-23

Guillet C, Rechsteiner M, Bellini E, et al (2020)

Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations.

Human pathology pii:S0046-8177(20)30020-4 [Epub ahead of print].

Juvenile papillomatosis (JP), the so-called Swiss cheese disease is a rare benign breast disease of young adults. An association (up to 28 %) with breast-cancer within the family of affected patients has been reported. A multinodular cystic breast-mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal-papillomas, usual ductal hyperplasia (UDH), ductectasias, perifocal sclerosing adenosis and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family-history in context with a comprehensive review of JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were female with a median-age of 38 years (26 to 50 years). Follow-up information was available in 11 of 13 patients. Sufficient paraffin embedded tissue and good DNA quality for next generation sequencing (NGS) was available in 10 patients. Paraffin blocks were microdissected in the area of intraductal proliferative disease, the tissue cores underwent NGS analysis using Oncomine Comprehensive Panel. In 5 of 10 patients, we found PIK3CA mutations, in 2 of 10 patients AKT1 mutations in known hotspot regions. Further mutations in MET, FGFR3, PTEN, ATM, NF1 and GNAS genes were detected in individual patients. Some of these mutations were present at high allelic frequencies suggesting germ line mutations. 2 of 3 patients with positive family history had PIK3CA mutation; one patient with positive family history had an AKT1 mutation. One patient who subsequently developed invasive ductal carcinoma in the contralateral breast possibly had a germ line ATM mutation. Our results confirm hotspot mutations in PIK3CA and AKT1 genes in JP associated with positive family history for breast cancer, although these mutations are not specific for JP. The genetic link between JP, positive family history and subsequent risk of breast cancer, needs further studies.

RevDate: 2020-02-22

Luo Y, Kishi S, Sasaki T, et al (2020)

Targeting claudin-4 enhances chemosensitivity in breast cancer.

Cancer science [Epub ahead of print].

Triple negative breast cancer (TNBC) possesses highly aggressive phenotype, treatment with limited options, and a poor prognosis. In this study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDCs (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and correlated with histological grade. In contrast, expression of CLDN4 correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors in association with increase in the intratumoral pH. Moreover, concurrent treatment of 4D3, PTX, or tamoxifen; or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects.

RevDate: 2020-02-21

Amichai-Hamburger Y, Mor Y, Wellingstein T, et al (2020)

The Personal Autonomous Car: Personality and the Driverless Car.

Cyberpsychology, behavior and social networking [Epub ahead of print].

Road traffic accidents, congestion and their ensuing issues are of international concern. A recent technological development to alleviate this situation is the autonomic car. A driverless vehicle will transport its passengers to their destinations. User experience would be enhanced by adapting the workings of the vehicle in line with the personality of its user. An autonomic car information system preference questionnaire was designed, focusing on different components of a futuristic information system. Participants comprised 155 students. The results demonstrated two factors: willingness to share information and need for control. A regression analysis on the automatic car preferences, personality (the Big 5), gender, and age showed that openness, consciousnesses, and age were related to different preferences. The results are assessed, followed by a discussion on personality in relation to the autonomic car.

RevDate: 2020-02-23

Sarah B, Ahmed G, Saloua B, et al (2020)

Nodular Scleritis Revealing Metastasis of Breast Cancer: Diagnosis Not to Be Neglected.

Case reports in ophthalmological medicine, 2020:8689463.

We report the case of ocular metastasis in a 48-year-old woman presenting left eye redness and pain. The patient was followed in another health institution for nodular scleritis and received systemic corticosteroids with moderate improvement. Medical history revealed that she was diagnosed three years ago with invasive ductal carcinoma of the left breast treated by tumorectomy with ganglion dissection. An ophthalmological examination found a hard scleral nodule with vascular architectural disorganization. A biopsy was performed, and the histopathological study revealed the presence of secondary tumor proliferation of poorly differentiated carcinoma of mammary cancer. This case report shows the fact that any unusual ocular presentation, even one simulating anterior scleritis, in a patient with a history of breast cancer should raise suspicion of metastasis.

RevDate: 2020-02-21

Yin S, Fan Y, He X, et al (2020)

The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum.

RNA biology [Epub ahead of print].

The tight gene expression regulation controls the development and pathogenesis of human malaria parasites Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in the dynamic gene expression. However, the landscape and related biological functions of nascent non-coding RNAs (ns-ncRNAs) are still poorly explored. Here we profiled the transcription dynamics of nascent RNAs by rRNA-depleted and stranded RNA sequencing over the course of 48-hour intraerythrocytic developmental cycle (IDC). We identified the genome-wide sources of a total of 2252 ns-ncRNAs, mostly originating from intergenic and untranslated regions of annotated genes. By integrating the nascent RNA abundances with ATAC-seq and ChIP-seq analysis, we uncovered the euchromatic microenvironment surrounding the ns-ncRNA loci, and revealed a positive correlation between ns-ncRNAs and corresponding mRNA abundances. Finally, by gene knock-down strategy, we showed that the cooperation of RNA exosome catalytic subunit PfDis3 and PfMtr4 cofactor played a major role in ns-ncRNAs degradation. Collectively, this study contributes to understanding of the potential roles of short-lived nascent ncRNAs in regulating gene expression in malaria parasites.

RevDate: 2020-02-20

Nissim M, Livny A, Barmatz C, et al (2020)

Effects of aquatic physical intervention on fall risk, working memory and hazard-perception as pedestrians in older people: a pilot trial.

BMC geriatrics, 20(1):74 pii:10.1186/s12877-020-1477-4.

BACKGROUND: Normal aging is associated with balance, mobility and working memory decline that increase fall risk and influence activity of daily living functions. Mounting evidence suggests that physical activity is beneficial for decreasing aging effects. Previous studies have focused on land-based physical activity. Research concerning the aquatic environment is scarce. The primary objectives of this three arm intervention pilot study were to examine the effects of an aquatic physical intervention program on balance, gait, fall risk and working memory among community-dwelling older individuals. The secondary objective was to examine the effects of an aquatic physical intervention program on safety of street-crossing among community-dwelling older individuals.

METHODS: Forty-two healthy participants aged 65 or older were enrolled into one of three intervention groups: aquatic physical intervention (API) (N = 13), on-land physical intervention (OLPI) (N = 14) or non-physical intervention (NPI) (N = 15). The intervention took place from 2018 until 2019 at Tel-Aviv University, Sheba medical center and Reich Center. The protocol included 30-min sessions twice a week for 12 weeks. Balance, gait and fall risk were assessed by the Tinneti test, working memory abilities were assessed by digit span and Corsi blocks tests and simulated safe streets-crossing was assessed by the hazard perception test for pedestrians. Testing and data collection was conducted at baseline, after six weeks and 12 weeks of intervention. All members of the professional team involved in evaluating participants were blind to the intervention group to which participants were allocated.

RESULTS: The differences in Tinetti balance (F (2, 39)=10.03, p < 0.01), fall risk (F (2, 39)=5.62, p0 > .05), digit span forward (F (2, 39)=8.85, p < 0.01) and Corsi blocks forward (F (2, 39)=3.54, p < 0.05) and backward (F (2, 39)=6.50, p < 0.05) scores after 12 weeks between the groups were significant. The API group showed improved scores. The differences in hazard perception test for pedestrians scores after 12 weeks of intervention between the groups were marginally significant (F (2, 39)=3.13, p = 0.055). The API group showed improved scores.

CONCLUSIONS: These findings may affect experts working with the elderly population when making decisions concerning therapeutic prevention interventions for the deficiencies of elderly patients. Older adults practicing aquatic physical activity could contribute to their increased safety.

TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov Registry NCT03510377. Date of registration: 10/31/2017.

RevDate: 2020-02-21

Sarikaya I, Sarikaya A, Albatineh AN, et al (2020)

Is there a difference in FDG PET findings of invasive ductal carcinoma of the breast with and without coexisting DCIS?.

Asia Oceania journal of nuclear medicine & biology, 8(1):27-35.

Objectives: Studies have reported that invasive ductal carcinoma (IDC) with coexisting ductal carcinoma in situ (DCIS) show lower metastatic potential and recurrence and better overall survival than pure IDC. In this study, we assessed F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images of patients with newly diagnosed IDC to determine if there is any difference in PET findings in IDC-DCIS and pure IDC cases.

Methods: FDG PET/CT images of patients with newly diagnosed IDC of the breast who subsequently underwent breast surgery and had histopathology result in our records were further evaluated. Tumor grade, pathological staging, and presence of DCIS were noted from the histopathology results. Standardized uptake value (SUV) of the primary tumor (SUVmax and SULmax), other hypermetabolic foci in the breast, and ipsilateral normal breast were measured. Presence of axillary and distant metastases was noted.

Results: Fifty seven (57) patients with IDC were included. Coexisting DCIS was present in 44 (IDC-DCIS) and not present in 13 (pure IDC) cases. Per histopathology, the primary tumor was unifocal in 33 IDC-DCIS (75%) and 12 pure IDC (92.3%) cases, and multifocal in 11 IDC-DCIS cases (25%), and 1 pure IDC case (7.7%). FDG uptake was multifocal in 20 IDC-DCIS cases (45.5%) and 1 pure IDC case (7.7%), and unifocal in 24 IDC-DCIS (54.5%), and 12 pure IDC (92.3%) cases. There was no significant difference in patient age, size of the primary tumor, SUVmax and SULmax of the primary tumor and SUVmax of the normal breast in IDC-DCIS and pure IDC cases (p>0.05). Pathology showed axillary metastasis in all 13 pure IDC (100%), and 27 IDC-DCIS (61.4%) cases. PET showed axillary uptake in 25 IDC-DCIS (56.8%), and 8 pure IDC (61.5%) cases, and abnormal/questionable distant uptake in 12 IDC-DCIS cases and 1 pure IDC case.

Conclusion: In our preliminary findings, multifocal breast FDG uptake and multifocal tumor appear to be more common in IDC-DCIS than pure IDC. There is no significant difference in SUV and size of the primary tumor in IDC-DCIS and pure IDC cases. Axillary metastases appear to be more common in pure IDC than IDC-DCIS cases.

RevDate: 2020-02-17

Granados K, Hüser L, Federico A, et al (2020)

T-type calcium channel inhibition restores sensitivity to MAPK inhibitors in de-differentiated and adaptive melanoma cells.

British journal of cancer pii:10.1038/s41416-020-0751-8 [Epub ahead of print].

BACKGROUND: Drug resistance remains as one of the major challenges in melanoma therapy. It is well known that tumour cells undergo phenotypic switching during melanoma progression, increasing melanoma plasticity and resistance to mitogen-activated protein kinase inhibitors (MAPKi).

METHODS: We investigated the melanoma phenotype switching using a partial reprogramming model to de-differentiate murine melanoma cells and target melanoma therapy adaptation against MAPKi.

RESULTS: Here, we show that partially reprogrammed cells are a less proliferative and more de-differentiated cell population, expressing a gene signature for stemness and suppressing melanocyte-specific markers. To investigate adaptation to MAPKi, cells were exposed to B-Raf Proto-Oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors. De-differentiated cells became less sensitive to MAPKi, showed increased cell viability and decreased apoptosis. Furthermore, T-type calcium channels expression increased in adaptive murine cells and in human adaptive melanoma cells. Treatment with the calcium channel blocker mibefradil induced cell death, differentiation and susceptibility to MAPKi in vitro and in vivo.

CONCLUSION: In summary, we show that partial reprogramming of melanoma cells induces de-differentiation and adaptation to MAPKi. Moreover, we postulated a calcium channel blocker such as mibefradil, as a potential candidate to restore sensitivity to MAPKi in adaptive melanoma cells.

RevDate: 2020-02-24

Kanwar N, Carmine-Simmen K, Nair R, et al (2020)

Amplification of a calcium channel subunit CACNG4 increases breast cancer metastasis.

EBioMedicine, 52:102646.

BACKGROUND: Previously, we found that amplification of chromosome 17q24.1-24.2 is associated with lymph node metastasis, tumour size, and lymphovascular invasion in invasive ductal carcinoma. A gene within this amplicon, CACNG4, an L-type voltage-gated calcium channel gamma subunit, is elevated in breast cancers with poor prognosis. Calcium homeostasis is achieved by maintaining low intracellular calcium levels. Altering calcium influx/efflux mechanisms allows tumour cells to maintain homeostasis despite high serum calcium levels often associated with advanced cancer (hypercalcemia) and aberrant calcium signaling.

METHODS: In vitro 2-D and 3-D assays, and intracellular calcium influx assays were utilized to measure tumourigenic activity in response to altered CANCG4 levels and calcium channel blockers. A chick-CAM model and mouse model for metastasis confirmed these results in vivo.

FINDINGS: CACNG4 alters cell motility in vitro, induces malignant transformation in 3-dimensional culture, and increases lung-specific metastasis in vivo. CACNG4 functions by closing the channel pore, inhibiting calcium influx, and altering calcium signaling events involving key survival and metastatic pathway genes (AKT2, HDAC3, RASA1 and PKCζ).

INTERPRETATION: CACNG4 may promote homeostasis, thus increasing the survival and metastatic ability of tumour cells in breast cancer. Our findings suggest an underlying pathway for tumour growth and dissemination regulated by CACNG4 that is significant with respect to developing treatments that target these channels in tumours with aberrant calcium signaling.

FUNDING: Canadian Breast Cancer Foundation, Ontario; Canadian Institutes of Health Research.

RevDate: 2020-02-17

Bartelt A, SB Widenmaier (2019)

Proteostasis in thermogenesis and obesity.

Biological chemistry pii:/j/bchm.just-accepted/hsz-2019-0427/hsz-2019-0427.xml [Epub ahead of print].

The proper production, degradation, folding and activity of proteins, proteostasis, is essential for any cellular function. From single cell organisms to humans, selective pressures have led to the evolution of adaptive programs that ensure proteins are properly produced and disposed of when necessary. Environmental factors such as temperature, nutrient availability, pathogens as well as predators have greatly influenced the development of mechanisms such the unfolded protein response, endoplasmic reticulum-associated protein degradation and autophagy, working together in concert to secure cellular proteostasis. In our modern society, the metabolic systems of the human body face the distinct challenge of changed diets, chronic overnutrition and sedentary lifestyles. Obesity and excess white adipose tissue accumulation are linked to a cluster of metabolic diseases and disturbed proteostasis is a common feature. Conversely, processes that promote energy expenditure such as exercise, shivering as well as non-shivering thermogenesis by brown adipose tissue (BAT) and beige adipocytes counteract metabolic dysfunction. Here we review basic concepts of proteostasis in obesity-linked metabolic diseases and focus on adipocytes, which are critical regulators of mammalian energy metabolism.

RevDate: 2020-02-15

Corona SP, Bortul M, Scomersi S, et al (2020)

Management of the axilla in breast cancer: outcome analysis in a series of ductal versus lobular invasive cancers.

Breast cancer research and treatment pii:10.1007/s10549-020-05565-x [Epub ahead of print].

INTRODUCTION: Axillary lymph node dissection (ALND) has been considered essential for the staging of breast cancer (BC). As the impact of tumor biology on clinical outcomes is recognized, a surgical de-escalation approach is being implemented. We performed a retrospective study focused on surgical management of the axilla in invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: 1151 newly diagnosed BCs, IDCs (79.6%) or ILCs (20.4%), were selected among patients treated at our Breast Cancer Unit from 2012 to 2018. Tumor characteristics and clinical information were collected and predictors of further metastasis after positive sentinel lymph node biopsy (SLNB) analyzed in relation to disease-free survival (DFS) and overall survival (OS).

RESULTS: 27.5% of patients with ILC had ≥ 3 metastatic lymph nodes at ALND after positive SLNB versus 11.48% of IDCs (p = 0.04). Risk predictors of further metastasis at ALND were the presence of > 2 positive lymph nodes at SLNB (OR = 4.72, 95% CI 1.15-19.5 p = 0.03), T3-T4 tumors (OR = 4.93, 95% CI 1.10-22.2, p = 0.03) and Non-Luminal BC (OR = 2.74, 95% CI 1.16-6.50, p = 0.02). The lobular histotype was not associated with the risk of further metastasis at ALND (OR = 1.62, 95% CI 0.77-3.41, p = 0.20).

CONCLUSIONS: ILC histology is not associated with higher risk of further metastasis at ALND in our analysis. However, surgical management decisions should be taken considering tumor histotype, biology and expected sensitivity to adjuvant therapies.

RevDate: 2020-02-23

Beetch M, Harandi-Zadeh S, Yang T, et al (2020)

DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer.

Scientific reports, 10(1):2415.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer unresponsive to traditional receptor-targeted treatments, leading to a disproportionate number of deaths. Invasive breast cancer is believed to evolve from non-invasive ductal carcinoma in situ (DCIS). Detection of triple-negative DCIS (TN-DCIS) is challenging, therefore strategies to study molecular events governing progression of pre-invasive TN-DCIS to invasive TNBC are needed. Here, we study a canine TN-DCIS progression and investigate the DNA methylation landscape of normal breast tissue, atypical ductal hyperplasia (ADH), DCIS and invasive breast cancer. We report hypo- and hypermethylation of genes within functional categories related to cancer such as transcriptional regulation, apoptosis, signal transduction, and cell migration. DNA methylation changes associated with cancer-related genes become more pronounced at invasive breast cancer stage. Importantly, we identify invasive-only and DCIS-specific DNA methylation alterations that could potentially determine which lesions progress to invasive cancer and which could remain as pre-invasive DCIS. Changes in DNA methylation during TN-DCIS progression in this canine model correspond with gene expression patterns in human breast tissues. This study provides evidence for utilizing methylation status of gene candidates to define late-stage (DCIS and invasive), invasive stage only or DCIS stage only of TN-DCIS progression.

RevDate: 2020-02-21

Dettogni RS, Stur E, Laus AC, et al (2020)

Potential biomarkers of ductal carcinoma in situ progression.

BMC cancer, 20(1):119.

BACKGROUND: Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.

METHODS: In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies.

RESULTS: The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis.

CONCLUSIONS: We propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.

RevDate: 2020-02-13

Mostyka M, Jessurun J, C Matrai (2020)

Sarcoid-Like Granulomatosis in a Patient With Breast Cancer Mimicking Refractory Metastatic Disease.

International journal of surgical pathology [Epub ahead of print].

Sarcoid-like granulomatosis is a known but rare adverse reaction to immune checkpoint inhibitors and chemotherapy in the treatment of advanced solid tumors. We present a case of a 29-year-old female with a pathologically confirmed poorly differentiated invasive ductal carcinoma of the breast with presumed metastases to the lungs, hilar lymph nodes, liver, and spleen. Despite appropriate chemotherapy, the patient developed pulmonary lesions that were interpreted on imaging studies as progression of malignancy. Autopsy revealed disseminated sarcoid-like granulomatosis with multiple noncaseating granulomata with associated fibrosis in the lungs, liver, and spleen. No residual invasive carcinoma or metastatic disease was identified. This case illustrates the difficulty in differentiating this nonneoplastic process from progressive disease in the clinical setting.

RevDate: 2020-02-19

Burusapat C, Buarabporn N, Wongchansom K, et al (2020)

Mammary adenoid cystic carcinoma presenting with Ductal carcinoma in situ and axillary lymph node metastasis.

Journal of surgical case reports, 2020(2):rjz362.

Mammary adenoid cystic carcinoma (ACC) is extremely rare tumors, comprising <0.1% of all breast cancers. Moreover, lymph node metastasis is <2% of mammary ACC. Here, we report a case of 51-year-old female presented with painful mass on her left breast and left axillary lymph node enlargement. Core needle biopsy revealed invasive ductal carcinoma. Left lumpectomy and axillary lymph nodes dissections were performed. The final pathological report showed triple-negative mammary ACC arising with high grade ductal carcinoma in situ (DCIS) and axillary lymph node metastasis. Immunohistochemistry study is useful in confirming a diagnosis. Given the rarity of this cancer, natural history of disease is still not clearly understood. Complete surgical excision is the mainstay of treatment. To our best knowledge, mammary ACC presenting with DCIS and axillary lymph node metastasis has never been reported and should be considered in the differential diagnosis of breast cancers.

RevDate: 2020-02-19

Moreno AC, Lin YH, Bedrosian I, et al (2020)

Outcomes after Treatment of Metaplastic Versus Other Breast Cancer Subtypes.

Journal of Cancer, 11(6):1341-1350.

Purpose: Metaplastic breast cancer (BC) is an uncommon yet aggressive histologic subtype of BC. We sought to identify factors associated with its diagnosis and compare the management and outcomes of metaplastic BC with those of other BCs and triple negative invasive ductal carcinoma in particular given how often it has a triple negative phenotype. Patients and Methods: We identified women diagnosed with invasive BC in 2010-2014 in the National Cancer Data Base, and used univariate analysis to compare baseline patient and tumor characteristics by BC subtype. Overall survival (OS) was estimated with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to identify independent predictors of OS. Results: Of 247,355 cases, 2,084 (0.8%) were metaplastic BC, 55,998 (23%) triple negative BC, and 77% other BC. Relative to non-metaplastic BC, women with metaplastic BC were more likely to be older at diagnosis (median age, 62 vs. 59 years), have ≥1 comorbid conditions (22% vs. 18%), and be on Medicare (41% vs. 33%; P<0.001). Metaplastic BCs tended to be basal-like (77%), and relative to triple-negative or other BC, metaplastic BC was associated with higher clinical T status (cT3-4, 18% vs. 11%, 8%), no clinical nodal involvement (cN0, 86%, 77%, 80%), no lymphovascular invasion (72%, 65%, 62%), and high-grade tumors (71%, 77%, 35%) (P<0.001). Most metaplastic BCs were treated with mastectomy (58%), sentinel lymph node dissection (65%), chest wall or breast irradiation (74%), and chemotherapy (75%) as adjuvant therapy (60%). At a median follow-up time of 44.5 months, OS rates were lower for metaplastic BC than for triple-negative or other BC across all clinical stages at 5 years (stage I, 85%, 87%, 91%; II, 73%, 77%, 87%; III, 43%, 53%, 75%) and at 3 years (Stage IV, 15%, 22%, 64%; P<0.001). On multivariate analysis, increasing age, advanced clinical stage, lymphovascular invasion, axillary (vs. sentinel) node dissection, and no radiation or chemotherapy were associated with worse outcomes in metaplastic BC. Extent of surgery affected survival for triple-negative and other BC but not for metaplastic BC. Conclusion: Outcomes for metaplastic BC continue to be worse than those for other BC subtypes despite modern treatments. Optimizing systemic therapy options, which was a significant predictor of survival, should be a priority in managing metaplastic BC.

RevDate: 2020-02-12

Kong J, Shahait AD, Kim S, et al (2020)

Radiation-induced undifferentiated pleomorphic sarcoma of the breast.

BMJ case reports, 13(2): pii:13/2/e232616.

Breast sarcoma is a rare form of malignancy that arises from connective tissue within the breast, comprising less than 5% of all sarcomas. They develop as primary tumours or as secondary following radiation therapy. Diagnosis can be challenging as breast sarcomas are often asymptomatic and resemble benign breast tissue changes. Radiation-induced breast sarcomas present in various forms with an average latency period of 10-20 years following initial radiation therapy. Angiosarcomas are the most common form, while other types such as undifferentiated pleomorphic sarcomas remain rare. Here, we report a case of radiation-induced undifferentiated pleomorphic breast sarcoma in a 75-year-old woman that developed nearly 20 years following breast conserving surgery and radiation for invasive ductal carcinoma. The patient initially noticed a mass in 2017 on self-examination. The mammogram, ultrasound and biopsy at the time showed a benign 2.2 cm nodular fasciitis without malignancy. The mass grew rapidly in the next 6 months to 5.6 cm and repeat biopsy diagnosed undifferentiated pleomorphic sarcoma. The mass abutted the pectoralis muscle but staging workup ruled out distant metastasis and the patient underwent wide local resection of the mass with clear margins. The patient subsequently underwent further postoperative radiation due to insufficient posterior margin width on wide local excision, as chest wall resection would have been required for a wider posterior margin. Prognosis for postradiation sarcomas is generally poor with 27%-36% 5-year survival, with surgical resection as the main line of treatment. The patient currently remains disease-free after 15 months of surveillance.

RevDate: 2020-02-11

Shahir M, Mahmoud Hashemi S, Asadirad A, et al (2020)

Effect of mesenchymal stem cell-derived exosomes on the induction of mouse tolerogenic dendritic cells.

Journal of cellular physiology [Epub ahead of print].

Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T-cell activation via direct cell-cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T-cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC-derived exosomes on the induction of mouse tolDCs, murine adipose-derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick-TC kits. BM-derived DCs (BMDCs) were prepared and cocultured with MSCs-derived exosomes (100 μg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1μg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester-labeled BALB/C-derived splenocytes p. Interleukin-6 (IL-6), IL-10, and transforming growth factor-β (TGF-β) release were measured by enzyme-linked immunosorbent assay. MSC-derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells (≤ .05). MSC-derived exosomes decrease IL-6 release but augment IL-10 and TGF-β release (p ≤ .05). Lymphocyte proliferation was decreased (p ≤ .05) in the presence of DCs treated with MSC-derived exosomes. CMSC-derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC-induced immune responses.

RevDate: 2020-02-14

Lee JS, Kim JS, Lee JH, et al (2019)

Prepectoral breast reconstruction with complete implant coverage using double-crossed acellular dermal matrixs.

Gland surgery, 8(6):748-757.

Background: Prepectoral implant-based breast reconstruction involving full implant coverage with an acellular dermal matrix (ADM) is more convenient, provides better aesthetic results, and carries lower risk of complications than does the traditional dual-plane method with an ADM. However, the recently reported technique usually involves full wrapping of the implant using a single, large ADM. We aimed to clarify the usefulness of an implant covering technique using two double-crossed ADMs.

Methods: We retrospectively evaluated the records of 23 breast cancer patients who, between February 2017 and March 2018, received skin-sparing or nipple-sparing mastectomy followed by immediate prepectoral implant-breast reconstruction. We assessed preoperative characteristics, cancer treatment parameters, incidence of postoperative complications (necrosis, capsular contracture, infection), and patient satisfaction at 12 months postoperatively.

Results: This cohort (mean age, 45.5 years; body mass index, 22.1 kg/m2; preoperative breast volume, 315.7 cc, excised mass weight, 291.4 g; silicone implant size, 252.4 cc) included 11 patients with ductal carcinoma in situ and 12 with invasive ductal carcinoma. Postoperatively, one patient received radiotherapy and nine received chemotherapy. Among postoperative complications, we noted capsular contracture (1/23, 4.3%), wound dehiscence (2/23, 8.7%), and seroma (3/23, 13.0%). Good patient satisfaction (mean score, 4.2-4.8 on the KNUH Breast Reconstruction Satisfaction Questionnaire) was obtained in all categories (breast symmetry, reconstructed breast size, shape, feel, pain, scar, self-confidence, sexual attractiveness, and overall satisfaction).

Conclusions: Prepectoral breast reconstruction involving complete implant coverage with double-crossed ADMs represents a good alternative to the traditional dual-plane subpectoral method, providing good patient satisfaction without adverse outcomes.

RevDate: 2020-02-14

English SW, Carabenciov ID, Lehman VT, et al (2019)

Zoster vasculopathy surveillance using intracranial vessel wall imaging.

Neurology. Clinical practice, 9(6):462-464.

RevDate: 2020-02-10

Satpathy G, Chandra GK, Manikandan E, et al (2020)

Pathogenic Escherichia coli (E. coli) detection through tuned nanoparticles enhancement study.

Biotechnology letters pii:10.1007/s10529-020-02835-y [Epub ahead of print].

OBJECTIVE: This study aims to detect pathogenic Escherichia coli (E. coli) bacteria using non-destructive fluorescence microscopy and micro-Raman spectroscopy.

RESULTS: Raman vibrational spectroscopy provides additional information regarding biochemical changes at the cellular level. We have used two nanomaterials zinc oxide nanoparticles (ZnO-NPs) and gold nanoparticles (Au-NPs) to detect pathogenic E. coli. The scanning electron microscope (SEM) with energy dispersive X-ray (EDAX) spectroscopy exhibit surface morphology and the elemental composition of the synthesized NPs. The metal NPs are useful contrast agents due to the surface plasmon resonance (SPR) to detect the signal intensity and hence the bacterial cells. The changes due to the interaction between cells and NPs are further correlated to the change in the surface charge and stiffness of the cell surface with the help of the fluorescence microscopic assay.

CONCLUSIONS: We conclude that when two E. coli strains (MTCC723 and MTCC443) and NPs are respectively mixed and kept overnight, the growth of bacteria are inhibited by ZnO-NPs due to changes in cell membrane permeability and intracellular metabolic system under fluorescence microscopy. However, SPR possessed Au-NPs result in enhanced fluorescence of both pathogens. In addition, with the help of Raman microscopy and element analysis, significant changes are observed when Au-NPs are added with the two strains as compared to ZnO-NPs due to protein, lipid and DNA/RNA induced conformational changes.

RevDate: 2020-02-14

Crocker C (2020)

Radiation-induced pemphigus in a patient with an invasive ductal carcinoma of the breast: a case report.

Oxford medical case reports, 2020(1):omaa001.

A 72-year-old woman with a known history of breast cancer was treated with adjuvant external beam radiation therapy. She initially developed radiation field localized blistering and erosions of the skin, before developing more widespread lesions. Immunofluorescence confirmed pemphigus vulgaris, which was responsive to corticosteroids. Pemphigus vulgaris is an autoimmune blistering disease of the skin that can rarely be associated with exposure to ionizing radiation.

RevDate: 2020-02-07

Söyleyici NA, Aslan F, Avcýkurt AS, et al (2020)

Importance of MACC1 expression in breast cancer and its relationship with pathological prognostic markers.

Indian journal of pathology & microbiology, 63(1):19-24.

Background: Metastasis associated colon cancer gene 1 (MACC1) is a gene that was first described as a c-Met transcription regulator causing the progression of colon cancer. In this study, protein and messenger RNA (mRNA) expression of MACC1 in breast cancer and its relationship with clinicopathological prognostic parameters were investigated.

Methods: Sixty-six cases with tumors underwent radical mastectomy for invasive ductal carcinoma and 25 control cases operated for mammoplasty were included in the study. In paraffin blocks of tumor and control tissues, MACC1 expression was investigated by the immunohistochemical method and Real-time polymerase chain reaction (Real-Time PCR). In addition, vascular endothelial growth factor (VEGF) expression was examined immunohistochemically in tumor tissues. The relationship between MACC1 expression in tumor tissues, clinicopathological prognostic parameters, and VEGF was investigated.

Results: In this study, protein and mRNA expressions of MACC1 were found to be higher in tumor tissues compared with normal breast tissues. MACC1 protein expression was also associated with significant poor prognostic markers, such as high histologic grade, ER negativity, and HER2 positivity. However, there was no correlation between MACC1 expression and VEGF.

Conclusion: According to these results, MACC1 expression may be a marker of breast carcinoma as well as an independent predictor of poor prognosis. In addition, MACC1 may not affect angiogenesis in breast cancer or even if it has an effect, it may not be associated with VEGF. However, it would be appropriate to support these results in a larger series by investigating in vivo and in vitro studies.

RevDate: 2020-02-07

Varma K, Chauhan A, Bhargava M, et al (2020)

Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma.

Indian journal of pathology & microbiology, 63(1):13-18.

Background: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet.

Materials and Methods: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association.

Results: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns.

Conclusion: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.

RevDate: 2020-02-11

Schwitzer JA, Dekker P, Kanuri A, et al (2019)

Post-mastectomy radiation arteritis in a patient presenting with upper extremity claudication.

AME case reports, 3:49.

Radiation arteritis is a rare but serious complication following radiation therapy for the treatment of breast cancer. We present the case of a 53-year-old female presenting with right upper extremity claudication 4 months following radiation therapy for the treatment of right breast cancer, stage 3b invasive ductal carcinoma. She was referred to vascular surgery and initial imaging with computed tomography angiography (CTA) revealed occlusion from the origin of the subclavian to axillary artery. We discuss the implications that these vascular findings have on potential breast reconstruction options.

RevDate: 2020-02-19

Mohd Sobri SN, Abdul Sani SF, Sabtu SN, et al (2020)

Structural Studies of Epithelial Mesenchymal Transition Breast Tissues.

Scientific reports, 10(1):1997.

At the supramolecular level, the proliferation of invasive ductal carcinoma through breast tissue is beyond the range of standard histopathology identification. Using synchrotron small angle x-ray scattering (SAXS) techniques, determining nanometer scale structural changes in breast tissue has been demonstrated to allow discrimination between different tissue types. From a total of 22 patients undergoing symptomatic investigations, different category breast tissue samples were obtained in use of surgically removed tissue, including non-lesional, benign and malignant tumour. Structural components of the tissues were examined at momentum transfer values between q = 0.2 nm-1 and 1.5 nm-1. From the SAXS patterns, axial d-spacing and diffuse scattering intensity were observed to provide the greatest discrimination between the various tissue types, specifically in regard to the epithelial mesenchymal transition (EMT) structural component in malignant tissue. In non-lesional tissue the axial period of collagen is within the range 63.6-63.7 nm (formalin fixed paraffin embedded (FFPE) dewaxed) and 63.4 (formalin fixed), being 0.9 nm smaller than in EMT cancer-invaded regions. The overall intensity of scattering from cancerous regions is a degree of magnitude greater in cancer-invaded regions. Present work has found that the d-spacing of the EMT positive breast cancer tissue (FFPE (dewaxed)) is within the range 64.5-64.7 nm corresponding to the 9th and 10th order peaks. Of particular note in regard to formalin fixation of samples is that no alteration is observed to occur in the relative differences in collagen d-spacing between non-lesional and malignant tissues. This is a matter of great importance given that preserved-sample and also retrospective study of samples is greatly facilitated by formalin fixation. Present results indicate that as aids in tissue diagnosis SAXS is capable of distinguishing areas of invasion by disease as well as delivering further information at the supramolecular level.

RevDate: 2020-02-07

Aminian A, Zajichek A, Arterburn DE, et al (2020)

Predicting 10-Year Risk of End-Organ Complications of Type 2 Diabetes With and Without Metabolic Surgery: A Machine Learning Approach.

Diabetes care pii:dc19-2057 [Epub ahead of print].

OBJECTIVE: To construct and internally validate prediction models to estimate the risk of long-term end-organ complications and mortality in patients with type 2 diabetes and obesity that can be used to inform treatment decisions for patients and practitioners who are considering metabolic surgery.

RESEARCH DESIGN AND METHODS: A total of 2,287 patients with type 2 diabetes who underwent metabolic surgery between 1998 and 2017 in the Cleveland Clinic Health System were propensity-matched 1:5 to 11,435 nonsurgical patients with BMI ≥30 kg/m2 and type 2 diabetes who received usual care with follow-up through December 2018. Multivariable time-to-event regression and random forest machine learning models were built and internally validated using fivefold cross-validation to predict the 10-year risk for four outcomes of interest. The prediction models were programmed to construct user-friendly web-based and smartphone applications of Individualized Diabetes Complications (IDC) Risk Scores for clinical use.

RESULTS: The prediction tools demonstrated the following discrimination ability based on the area under the receiver operating characteristic curve (1 = perfect discrimination and 0.5 = chance) at 10 years in the surgical and nonsurgical groups, respectively: all-cause mortality (0.79 and 0.81), coronary artery events (0.66 and 0.67), heart failure (0.73 and 0.75), and nephropathy (0.73 and 0.76). When a patient's data are entered into the IDC application, it estimates the individualized 10-year morbidity and mortality risks with and without undergoing metabolic surgery.

CONCLUSIONS: The IDC Risk Scores can provide personalized evidence-based risk information for patients with type 2 diabetes and obesity about future cardiovascular outcomes and mortality with and without metabolic surgery based on their current status of obesity, diabetes, and related cardiometabolic conditions.

RevDate: 2020-02-05

Kennedy SA, Faughnan ME, Vozoris NT, et al (2020)

Reperfusion of Pulmonary Arteriovenous Malformations Following Embolotherapy: A Randomized Controlled Trial of Detachable Versus Pushable Coils.

Cardiovascular and interventional radiology pii:10.1007/s00270-020-02422-8 [Epub ahead of print].

PURPOSE: To compare 1 year post-embolization reperfusion rates in pulmonary arteriovenous malformations (PAVMs) treated with the 0.035″ Interlock™ Fibered IDC™ Occlusion System coils (IDC) (Boston Scientific, Marlborough, Massachusetts) versus 0.035″ Nester coils (Cook Medical Inc., Bloomington, Indiana).

MATERIALS AND METHODS: A randomized controlled trial was performed randomizing individual PAVMs to treatment with IDC versus Nester coils at the largest hereditary hemorrhagic telangiectasia center in Canada. The primary outcome was CT evidence of reperfusion at 1 year. Secondary outcomes included periprocedural complications, fluoroscopy time and contrast volume.

RESULTS: Our study was terminated prematurely due to slow recruitment and subsequent expiration of funding. A total of 46 PAVMs in 25 patients (64% female) were included in our study; 26 randomized to Nester coils and 20 randomized to IDC. One patient was lost to follow-up. At a mean follow-up of 421.2 ± 215.7 days, no significant difference in PAVM reperfusion was detected between Nester coils and IDC (0% vs. 5.6%, p > 0.05). No major periprocedural complications were noted in either group. Fluoroscopy time (Nester: 15.0 ± 11.8 min vs. IDC 16.0 ± 5.4 min, p > 0.05) and contrast volume (Nester: 80.3 ± 36.5 ml vs. IDC 87.3 ± 51.7 ml, p > 0.05) utilized did not differ between groups.

CONCLUSION: No significant difference was detected in PAVM reperfusion rates, periprocedural complication rates, contrast volume utilization or fluoroscopy time following embolization with IDC and Nester coils.

RevDate: 2020-02-05

Wu J, Ding S, Lin L, et al (2020)

Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study.

Cancer research and treatment : official journal of Korean Cancer Association pii:crt.2019.387 [Epub ahead of print].

Purpose: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).

Materials and Methods: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay of 21 genes was conducted to calculate the recurrence score (RS). Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log rank test.

Results: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).

Conclusion: RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

RevDate: 2020-02-11

Tsay AJ, Paine AR, Lighthall JG, et al (2020)

A possible pitfall of Mohs surgery in collision tumor diagnosis: A case of a squamous cell carcinoma of the scalp overlying a metastatic breast lesion of the skull.

JAAD case reports, 6(2):119-121.

RevDate: 2020-02-18

Milne DM, Sookar N, Umakanthan S, et al (2020)

Primary Osteosarcoma of the Breast in a Patient Treated Previously for Invasive Ductal Carcinoma: An Unusual Presentation of a Very Rare Primary Breast Malignancy.

Case reports in surgery, 2020:1594127.

Primary osteogenic sarcoma of the breast is a rare clinical entity with few cases described in the literature. Unfortunately, the prognosis for these patients is poor when compared to invasive carcinomas of the breast. We report a case of a 58-year-old female who developed a primary osteogenic sarcoma of the breast five years after being treated for invasive carcinoma of the ipsilateral breast without the use of radiotherapy.

RevDate: 2020-02-11

Scholl AR, MB Flanagan (2020)

Educational Case: Invasive Ductal Carcinoma of the Breast.

Academic pathology, 7:2374289519897390.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

RevDate: 2020-02-04

Komaei I, Guccione F, Sarra F, et al (2019)

Radiation-induced undifferentiated pleomorphic sarcoma of the breast: a rare but serious complication following breast-conserving therapy. A case report and literature review.

Il Giornale di chirurgia, 40(6):544-550.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) of the breast is an extremely rare, but aggressive subtype of sarcoma that can develop in radiotherapy (RT)-treated breast cancer patients. Due to the low incidence, there are many uncertainties regarding the adequate management of these tumors. We present a rare case of radiation-induced UPS in a 63-year-old woman who had undergone breast conserving therapy for invasive ductal carcinoma of the left breast, six years prior to presentation.

CASE PRESENTATION: A 63-year-old woman presented with a rapidly growing left breast mass. She had been diagnosed with invasive ductal carcinoma of the left breast for which she underwent a left upper outer quadrantectomy and ipsilateral axillary dissection followed by RT, six years previously. During her routine oncologic follow-up, the mammography revealed a dense, nodular opacity with microcalcifications. The breast ultrasound (US) confirmed the presence of the nodule. US-guided fine needle aspiration biopsy was performed and the diagnosis of UPS was made, the reason for which the patient underwent wide local excision of the left breast.

CONCLUSION: The diagnosis of RT-induced UPS is challenging and often missed due to the low incidence, long latency period, unspecific imaging findings, and difficulties in clinical and histological detection of these lesions. These tumors should be considered in differential diagnoses of rapidly-growing breast masses in previously RT-treated breast cancer patients, as they can mimic the local recurrence of the primary tumor. Since the prevalence of breast-conserving surgery followed by RT has been increasing, the careful monitoring of at risk patients is of utmost importance, as UPSs are highly aggressive tumors associated with very poor outcomes.

RevDate: 2020-02-10

Selvakumaran V, Hou R, Baker JA, et al (2020)

Predicting Upstaging of DCIS to Invasive Disease: Radiologists's Predictive Performance.

Academic radiology pii:S1076-6332(19)30623-3 [Epub ahead of print].

RATIONALE AND OBJECTIVES: The purpose of this study is to quantify breast radiologists' performance at predicting occult invasive disease when ductal carcinoma in situ (DCIS) presents as calcifications on mammography and to identify imaging and histopathological features that are associated with radiologists' performance.

MATERIALS AND METHODS: Mammographically detected calcifications that were initially diagnosed as DCIS on core biopsy and underwent definitive surgical excision between 2010 and 2015 were identified. Thirty cases of suspicious calcifications upstaged to invasive ductal carcinoma and 120 cases of DCIS confirmed at the time of definitive surgery were randomly selected. Nuclear grade, estrogen and progesterone receptor status, patient age, calcification long axis length, and breast density were collected. Ten breast radiologists who were blinded to all clinical and pathology data independently reviewed all cases and estimated the likelihood that the DCIS would be upstaged to invasive disease at surgical excision. Subgroup analysis was performed based on nuclear grade, long axis length, breast density and after exclusion of microinvasive disease.

RESULTS: Reader performance to predict upstaging ranged from an area under the receiver operating characteristic curve (AUC) of 0.541-0.684 with a mean AUC of 0.620 (95%CI: 0.489-0.751). Performances improved for lesions smaller than 2 cm (AUC: 0.676 vs 0.500; p = 0.002). The exclusion of microinvasive cases also improved performance (AUC: 0.651 vs 0.620; p = 0.005). There was no difference in performance based on breast density (p = 0.850) or nuclear grade (p = 0.270) CONCLUSION: Radiologists were able to predict invasive disease better than chance, particularly for smaller DCIS lesions (<2 cm) and after the exclusion of microinvasive disease.

RevDate: 2020-01-30
CmpDate: 2020-01-30

Knowles S, Maxwell J, Lumsden A, et al (2020)

An alternative to standard lumpectomy: a 5-year case series review of oncoplastic breast surgery outcomes in a Canadian setting.

Canadian journal of surgery. Journal canadien de chirurgie, 63(1):E46-E51.

Background: Oncoplastic surgery (OPS) is becoming the new standard of care for breast-conserving surgery (BCS). It has become increasingly popular in Europe; however, it has not yet been widely accepted in North America. This study aims to describe the experience with OPS at a Canadian tertiary care centre.

Methods: This study is a retrospective case series consisting of consecutive OPS cases at a single Canadian centre, the Royal Victoria Regional Health Centre in Barrie, Ontario, between 2009 and 2015.

Results: A total of 275 women who consecutively underwent OPS were included. The average size of the tumour was 17 mm (standard deviation [SD] 13 mm; range 0–110 mm). The average specimen weight was 155 g (SD 146 g; range 15–1132 g). Invasive ductal carcinoma was the most common diagnosis (237 patients, 86.2%), followed by ductal carcinoma in situ (18 patients, 6.6%) and then invasive lobular carcinoma (15 patients, 5.5%). A positive margin was recorded in 37 (13.5%) patients. Immediate postoperative complications included seroma and edema (32.7%), wound infection (13.1%), hematoma (8.7%) and delayed wound healing (6.5%). A delay to adjuvant therapy due to postoperative complications occurred in 7 of 217 (3.2%) patients. The median follow-up was 18 months. There were local and distant recurrences in 9 (3.3%) and 2 (0.7%) patients, respectively. Overall survival was 99.3%.

Conclusion: The findings of this study are comparable to results in the literature on OPS and demonstrate that OPS is an attractive alternative to standard lumpectomy for Canadian general surgeons who treat breast cancer.

RevDate: 2020-02-05

Assefa T, Zhang J, Chowda-Reddy RV, et al (2020)

Deconstructing the genetic architecture of iron deficiency chlorosis in soybean using genome-wide approaches.

BMC plant biology, 20(1):42.

BACKGROUND: Iron (Fe) is an essential micronutrient for plant growth and development. Iron deficiency chlorosis (IDC), caused by calcareous soils or high soil pH, can limit iron availability, negatively affecting soybean (Glycine max) yield. This study leverages genome-wide association study (GWAS) and a genome-wide epistatic study (GWES) with previous gene expression studies to identify regions of the soybean genome important in iron deficiency tolerance.

RESULTS: A GWAS and a GWES were performed using 460 diverse soybean PI lines from 27 countries, in field and hydroponic iron stress conditions, using more than 36,000 single nucleotide polymorphism (SNP) markers. Combining this approach with available RNA-sequencing data identified significant markers, genomic regions, and novel genes associated with or responding to iron deficiency. Sixty-nine genomic regions associated with IDC tolerance were identified across 19 chromosomes via the GWAS, including the major-effect quantitative trait locus (QTL) on chromosome Gm03. Cluster analysis of significant SNPs in this region deconstructed this historically prominent QTL into four distinct linkage blocks, enabling the identification of multiple candidate genes for iron chlorosis tolerance. The complementary GWES identified SNPs in this region interacting with nine other genomic regions, providing the first evidence of epistatic interactions impacting iron deficiency tolerance.

CONCLUSIONS: This study demonstrates that integrating cutting edge genome wide association (GWA), genome wide epistasis (GWE), and gene expression studies is a powerful strategy to identify novel iron tolerance QTL and candidate loci from diverse germplasm. Crops, unlike model species, have undergone selection for thousands of years, constraining and/or enhancing stress responses. Leveraging genomics-enabled approaches to study these adaptations is essential for future crop improvement.

RevDate: 2020-02-24

Billena C, Padia S, O'Brien B, et al (2020)

Radiation recall dermatitis after treatment of stage IV breast cancer with nivolumab: a case report.

Immunotherapy, 12(2):123-130.

Radiation recall dermatitis (RRD) is an uncommon dermatologic reaction provoked notably by chemotherapy in an area of skin irradiated weeks to years prior. We report a case of RRD with nivolumab in a woman with breast cancer. The patient was diagnosed with invasive ductal carcinoma of the left breast with an isolated spinal metastasis approached in an oligometastatic fashion with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant radiotherapy. Unfortunately, after progression of bony metastases treated with radiotherapy, the patient received nivolumab and subsequently developed a rash corresponding to the adjuvant radiation field. This case highlights the unpredictable nature and characteristic rash of RRD. It is an important differential diagnosis for multidisciplinary teams who also see chemotherapy-induced dermatitis and immune-related adverse events.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Cancer is the generic name for more than 100 diseases in which cells begin to grow and divide in an uncontrolled manner. Usually, when cells get too old or damaged, they die and new cells take their place. Cancer begins when genetic changes impair this orderly process so that some cells start to grow uncontrollably. The Emperor of All Maladies is a "biography" of cancer — from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence. This is a must read book for anyone with an interest in cancer. R. Robbins

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