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Purpose: Oxidative stress-responsive kinase 1 (OSR1) plays a crucial role in regulating diverse cellular pathophysiologic functions, including ion homeostasis, development, differentiation, angiogenesis, invasive migration, and metastasis. Regardless, the clinical significance of OSR1 in breast cancer is scarce. The current study was conducted to evaluate the effect of OSR1 on the prognosis of patients with breast cancer with a long-term follow-up., Methods: OSR1 expression in formalin-fixed and paraffin-embedded tissue specimens was analyzed. These specimens were collected from 551 evaluable breast cancer cases by immunohistochemistry (IHC). OSR1 expression was dichotomized based on the H-score in IHC. The effects of OSR1 levels on the clinicopathological attributes and survival prediction in patients with breast cancer were explored., Results: Among 551 specimens, 183 (33.2%) exhibited high expression of OSR1 in tumor cells. High OSR1 levels were markedly correlated with histologic grade (P = 0.035), ER (P < 0.001) and PgR (P = 0.043) expression, lymph node involvement (P < 0.001), TNM stage (P < 0.001), and axillary surgery procedures (P = 0.003). Univariate analysis results indicate that patients with high OSR1 expression had significantly poor overall survival (P < 0.001), distant disease-free survival (P < 0.001), and breast cancer-specific survival (P < 0.001). Multivariable Cox regression analyses suggest that OSR1 expression was an independent predictive marker of poor prognosis and lymph node metastasis (HR 3.224, 95% CI 1.182-8.702, P = 0.023) in patients with breast cancer., Conclusions: Our findings indicate that OSR1 is a significantly independent prognosis index for patients with breast cancer with respect to distant disease-free survival, overall survival, and breast cancer-specific survival. High OSR1 expression caused an increase in deaths specifically attributed to breast cancer and was related to increased lymph node metastasis. However, the precise cellular mechanisms for OSR1 in breast cancer require further research.

Background: In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant., Methods: Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors., Results: In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups., Conclusions: Our findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy.

Background: A prognostic model combining biomarkers of metaphase-anaphase transition of the cell cycle was developed for invasive breast cancer. The prognostic value and clinical applicability of the model was evaluated in comparison with the routine prognosticators of invasive breast carcinoma., Methods: The study comprised 1135 breast cancer patients with complete clinical data and up to 22-year follow-up. Regulators of metaphase-anaphase transition were detected immunohistochemically and the biomarkers with the strongest prognostic impacts were combined into a prognostic model. The prognostic value of the model was tested and evaluated in separate patient materials originating from two Finnish breast cancer centers., Results: The designed model comprising immunoexpressions of Securin, Separase and Cdk1 identified 8.4-fold increased risk of breast cancer mortality (p < 0.0001). A survival difference exceeding 15 years was observed between the majority (> 75%) of patients resulting with favorable as opposed to unfavorable outcome of the model. Along with nodal status, the model showed independent prognostic impact for all breast carcinomas and for subgroups of luminal, N+ and N- disease., Conclusions: The impact of the proposed prognostic model in predicting breast cancer survival was comparable to nodal status. However, the model provided additional information in N- breast carcinoma in identifying patients with aggressive course of disease, potentially in need of adjuvant treatments. Concerning N+, in turn, the model could provide evidence for withholding chemotherapy from patients with favorable outcome.

Purpose: The purpose of this study is to predict risk of local recurrence (LR) in ductal carcinoma in situ (DCIS) with a new visualization and quantification approach using centrosome amplification (CA), a cancer cell-specific trait widely associated with aggressiveness., Experimental Design: This first-of-its-kind methodology evaluates the severity and frequency of numerical and structural CA present within DCIS and assigns a quantitative centrosomal amplification score (CAS) to each sample. Analyses were performed in a discovery cohort (DC, n = 133) and a validation cohort (VC, n = 119)., Results: DCIS cases with LR exhibited significantly higher CAS than recurrence-free cases. Higher CAS was associated with a greater risk of developing LR (HR, 6.3 and 4.8 for DC and VC, respectively; P < 0.001). CAS remained an independent predictor of relapse-free survival (HR, 7.4 and 4.5 for DC and VC, respectively; P < 0.001) even after accounting for potentially confounding factors [grade, age, comedo necrosis, and radiotherapy (RT)]. Patient stratification using CAS ( P < 0.0001) was superior to that by Van Nuys Prognostic Index (VNPI; HR for CAS = 6.2 vs. HR for VNPI = 1.1). Among patients treated with breast-conserving surgery alone, CAS identified patients likely to benefit from adjuvant RT., Conclusions: CAS predicted 10-year LR risk for patients who underwent surgical management alone and identified patients who may be at low risk of recurrence, and for whom adjuvant RT may not be required. CAS demonstrated the highest concordance among the known prognostic models such as VNPI and clinicopathologic variables such as grade, age, and comedo necrosis., (©2020 American Association for Cancer Research.)

Background: The purpose of this study was to investigate whether combining pembrolizumab with palliative radiation therapy (RT) improves outcomes in patients with hormone receptor-positive (HR + ) metastatic breast cancer (MBC)., Patients and Methods: Eligible patients had HR + /human epidermal growth factor receptor 2-negative MBC; were candidates for RT to ≥ 1 bone, soft tissue, or lymph node lesion; and had ≥ 1 lesion outside the RT field. Patients received 200 mg pembrolizumab intravenously 2 to 7 days prior to RT and on day 1 of repeating 21-day cycles. RT was delivered to a previously unirradiated area in 5 treatments each of 4 Gy. The primary endpoint was objective response rate. The study used a 2-stage design: 8 women were enrolled into the first stage, and if at least 1 of 8 patients experienced an objective response, 19 more would be enrolled. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory endpoints included association of overall response rate with programmed death-ligand 1 status and tumor-infiltrating lymphocytes., Results: Eight patients were enrolled in stage 1. The median age was 59 years, and the median prior lines of chemotherapy for metastatic disease was 2. There were no objective responses, and the study was closed to further accrual. The median progression-free survival was 1.4 months (95% confidence interval, 0.4-2.1 months), and the median overall survival was 2.9 months (95% confidence interval, 0.9-3.6 months). All-cause adverse events occurred in 87.5% of patients, including just 1 grade 3 event (elevation of aspartate aminotransferase)., Conclusions: RT combined with pembrolizumab did not produce an objective response in patients with heavily pre-treated HR + MBC. Future studies should consider alternative radiation dosing and fractionation in patients with less heavily pre-treated HR + MBC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We previously reported that breast conservation was feasible for women with large or irregularly shaped breast cancers when tumor resection was guided by multiple localizing wires. We now report long-term outcomes of multiple-wire versus single-wire localized lumpectomies for breast cancer., Patients and Methods: We retrospectively reviewed wire-localized lumpectomies at our institution from May 2000 to November 2006. Rates of ipsilateral in-breast tumor recurrence, metastasis, and subsequent unplanned diagnostic imaging and biopsy were compared between multiple-wire and single-wire cohorts., Results: We identified 112 multiple-wire and 160 single-wire breast cancer lumpectomies that achieved clear margins. Median age was 64 years in the multiple-wire cohort and 57 years in the single-wire cohort. Mean lumpectomy volume was 75 mL in multiple-wire patients and 49 mL in single-wire patients (P = .003). Invasive tumor size, axillary node status, and use of radiation and systemic therapy were similar, but the multiple-wire group had more patients with ductal carcinoma-in-situ only (38% vs. 28%). At 108 months' median follow-up, there was no significant difference in local or distant recurrence rates between multiple-wire and single-wire cohorts. Six (5%) multiple-wire patients and 6 (4%) single-wire patients had local recurrences and 3 (3%) multiple-wire and 5 (3%) single-wire patients developed metastatic disease. Unplanned diagnostic imaging was required for 53 (47%) multiple-wire and 65 (41%) single-wire patients. Subsequent ipsilateral biopsy occurred in 15 (13%) multiple-wire and 19 (12%) single-wire patients., Conclusion: Breast-conserving surgery with multiple localizing wires is a safe alternative to mastectomy for breast cancer patients with large mammographic lesions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The objective of this study is to analyse the relative survival with breast cancer in women diagnosed after new treatments were generalised and to ascertain the current effect that tumour characteristics such as grade, stage or subtype have on survival as well as the new AJCC-pathological prognostic score., Methods: The breast cancer MCC-Spain follow-up study is a prospective cohort study of 1685 incident breast cancer cases. Women between 20 and 85 years old were recruited between the years 2008 and 2013 in 18 hospitals located in 10 Spanish provinces and they have been followed until 2017/2018. Relative survival was estimated after 3, 5 and 8 years of follow-up using Ederer II method. In addition, Weibull regression adjusted by age, hospital, grade and stage was used to investigate prognosis factors., Results: Among components of TNM staging system, tumour size greater than 50 mm (i.e. T3 or T4) more than doubled the risk of dying, while N3 nodal involvement and presence of metastasis had a huge effect on mortality. The AJCC pathological prognostic score strongly correlated with survival; thus, hazard ratios increased as the score rose, being 2.31, 4.00, 4.94, 7.92, 2.26, 14.9 and 58.9 for scores IB, IIA, IIB, IIIA, IIIB, IIIC and IV, respectively., Conclusion: Both TNM staging and histological/molecular biomarkers are associated with overall survival in Spanish women with breast cancer; when both are combined in the AJCC pathological prognosis score, the prognostic value improved with risk indices that increased rapidly as the pathological prognosis score increased.

Background: Ultrafast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived kinetic parameters have demonstrated at least equivalent accuracy to standard DCE-MRI in differentiating malignant from benign breast lesions. However, it is unclear if they have any efficacy as prognostic imaging markers. The aim of this study was to investigate the relationship between ultrafast DCE-MRI-derived kinetic parameters and breast cancer characteristics., Methods: Consecutive breast MRI examinations between February 2017 and January 2018 were retrospectively reviewed to determine those examinations that meet the following inclusion criteria: (1) BI-RADS 4-6 MRI performed on a 3T scanner with a 16-channel breast coil and (2) a hybrid clinical protocol with 15 phases of ultrafast DCE-MRI (temporal resolution of 2.7-4.6 s) followed by early and delayed phases of standard DCE-MRI. The study included 125 examinations with 142 biopsy-proven breast cancer lesions. Ultrafast DCE-MRI-derived kinetic parameters (maximum slope [MS] and bolus arrival time [BAT]) were calculated for the entire volume of each lesion. Comparisons of these parameters between different cancer characteristics were made using generalized estimating equations, accounting for the presence of multiple lesions per patient. All comparisons were exploratory and adjustment for multiple comparisons was not performed; P values < 0.05 were considered statistically significant., Results: Significantly larger MS and shorter BAT were observed for invasive carcinoma than ductal carcinoma in situ (DCIS) (P < 0.001 and P = 0.008, respectively). Significantly shorter BAT was observed for invasive carcinomas with more aggressive characteristics than those with less aggressive characteristics: grade 3 vs. grades 1-2 (P = 0.025), invasive ductal carcinoma vs. invasive lobular carcinoma (P = 0.002), and triple negative or HER2 type vs. luminal type (P < 0.001)., Conclusions: Ultrafast DCE-MRI-derived parameters showed a strong relationship with some breast cancer characteristics, especially histopathology and molecular subtype.

Invasive ductal carcinoma (IDC) is the most common breast cancer. Our study used gene microarray data to select differentially expressed genes between normal and IDC mammary tissues. From these, we selected genes related to the proliferation of tumor cells and compared their prognostic value with known biomarker Ki67 for IDC. Analysis of publicly available Gene Expression Omnibus (GEO) data revealed 24 differentially expressed genes (DEGs) in normal and 31 DEGS in IDC tissues that were used for further analyses. Gene chip analysis software was used to identify DEGs. DEG profiles were confirmed using quantitative PCR (qPCR). DEG functions where shown to be related to cell proliferation. We confirmed MCM3 expression using immunohistochemical staining in 45 IDC patients. The relationship between MCM3 expression and survival was investigated using Kaplan-Meier survival curves and Cox proportional hazard regression models. A total of 1307 differentially expressed genes were identified between IDC and normal tissues, which were enriched in 32 Gene Ontology (GO) terms and 9 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. qPCR demonstrated that both COL1A1 and MCM3 were significantly up-regulated in IDC tissues, of which only MCM3 was related to cell proliferation. Ki67 is closely associated with the tumor grade, ER status, PR status and HER2 status, while MCM3 was shown to relate to tumor size, lymph node, and PR status. There was significant association between survival and MCM3, but not for Ki67. High MCM3 expression demonstrated statistically significant associations with poor prognosis in IDC patients. Findings from the gene microarray data analysis confirmed that MCM3 is associated with the response to cell proliferation. MCM3 represents a better proliferation marker than Ki67 making it a valuable prognostic tool that is independent of ER and HER2 status.

Purpose: The aim of this study is to evaluate the prognostic value of the Mitotic Activity Index (MAI) in combination with the human epidermal growth factor receptor (Her2) for distant metastases-free survival (DMFS) and disease-specific survival (DSS) in breast cancer and compare it with the immunohistochemically (IHC) profile types., Methods: Analyses were based on 2.923 breast-conserving breast cancer specimens with known MAI, Her2 status, and hormone receptor status, resulting in 2.678 Her2MAI combinations, MAI ≤ 12/Her2negative, MAI > 12/Her2negative, MAI > 12/Her2positive, and MAI ≤ 12/Her2positive, and 2.560 IHC profile types, luminal A, luminal B, triple negative, and non-luminal Her2positive., Results: For DMFS, the MAI > 12/Her2negative combination showed a significantly worse outcome in multivariate analyses compared to the MAI ≤ 12/Her2negative combination. None of the IHC profile types showed significantly different outcomes for DMFS and DSS as compared to luminal A. We performed a separate analysis on age and lymph node status. The significance of MAI > 12/Her2negative seems to be limited to women ≤ 55 years for both DMFS and DSS. However, with respect to DSS, this seems to be limited to node negative cases. The IHC profile types for DSS, luminal B showed a significantly worse outcome for women > 55 years compared to that for luminal A, although it showed rather wide confidence interval., Conclusion: The MAI > 12/Her2negative combination seems to be a strong prognosticator for DMFS and DSS, particularly for women ≤ 55 years. However, none of the IHC profile types seems to be a prognosticator in breast cancer.

Background: African American women (AAW) die more frequently from estrogen receptor (ER) positive breast cancer than European American women (EAW). We investigated the relationship between race, percent ER staining, treatment, and clinical outcomes., Methods: Percent ER staining (weakly ER+: 1-10%, moderately ER+: 11-50%, strongly ER+: > 50%) was abstracted from pathology reports for 1573 women with ER+/HER2- invasive breast cancer treated at a single cancer center in Detroit, MI from 2010 to 2017. Clinical outcomes and tumor characteristics were obtained from the Metropolitan Detroit Cancer Surveillance System. Associations of ER levels with demographic and clinical characteristics were evaluated using logistic regression. Overall and breast cancer-specific (BCS) survival were evaluated using Cox proportional hazards models., Results: AAW were more likely to have tumors with lower ER staining levels than EAW (weakly ER+: Odds ratio (OR) 2.19, p = 0.019; moderately ER+: OR 2.80, p = 0.005). Women with weakly compared to strongly ER+ tumors were less likely to receive endocrine therapy (ET) regardless of race (OR 0.79, p < 0.001). Mortality was predicted by both AA race (Overall hazard ratio (HR) = 1.72, p < 0.001; BCS HR 1.45, p = 0.08) and low (1-50%) ER (Overall HR 1.57, p = 0.083; BCS HR 2.11, p = 0.017) adjusting for clinic-pathologic characteristics. ET was associated with improved BCS survival in all women (1-50%: HR 0.11, p < 0.001; > 50%: HR 0.24, p < 0.001)., Conclusion: The biology of ER+/HER2- tumors varies by race, although this does not appear to account for racial differences in survival. Although ET substantially reduces mortality among women with weakly ER+ tumors, these women are less likely to be treated with ET and have poorer outcomes.

Background: Concern for cardiovascular disease (particularly atrial fibrillation-AF) among women with breast cancer is becoming a major issue. We aimed at determining the incidence of cardiovascular disease events (AF, arterial and cardiac events, venous-thromboembolism-VTE) in patients diagnosed with breast cancer, and assessing potential risk factors., Methods: We reviewed medical records of all patients diagnosed with breast cancer from 2010 to 2011 in our cancer center. Baseline characteristics of patients and tumors were collected. The main outcome was the occurrence of cardiovascular disease events (AF, VTE, arterial and cardiac events) during the 5-years follow-up., Results: Among the 682 breast cancer patients, 22 (3.2%) patients had a history of atrial fibrillation. Thirty-four patients (5%) presented at least one cardiovascular disease event, leading to a cumulative incidence of 5.8% events at 5-years ([3.8-7.7] CI 95%), with most of them occurring in the first 2 years. AF cumulative incidence was 1.1% ([0.1-2.1] CI 95%). Factors associated with the occurrence of cardiovascular disease events (including AF) were an overexpression of HER-2 (HR 2.6 [1.21-5.56] p < 0.011), UICC-stage III tumors or more (HR 5.47 [2.78-10.76] p < 0.001) and pre-existing cardiovascular risk factors (HR 2.91 [1.36-6.23] p < 0.004)., Conclusion: The incidence of cardiovascular disease events was 5.8% ([3.8-7.7] CI 95%), with HER-2 over-expression, UICC-stage III tumors or more and pre-existing cardiovascular diseases being associated with them. These findings call for the development of preventive strategies in patients diagnosed with breast cancer.

Background: Breast adenomyoepithelioma (AME) is rare. We sought to evaluate clinical characteristics, treatment, and outcomes of a contemporary patient cohort stratified by histology., Methods: We queried health records containing "adenomyoepithelioma" between 2000 and 2018. Histology was confirmed with centralized review and classified into benign, atypical, and malignant. Clinical characteristics, demographics, treatment, and oncologic outcomes were compared., Results: Our query yielded 24 patients with adenomyoethelioma. Histologic diagnosis was confirmed in 12 (benign n = 6, atypical n = 3, malignant n = 3). Excision (n = 11) was the usual initial treatment, with margin status available in 10 patients. Mean follow up was 44 months (range 1-138 months) with no local recurrence observed. Two patients with benign AME presented with concurrent contralateral breast cancer, and one with malignant AME died of metastatic AME., Conclusion: Wide excision of atypical and malignant AME is recommended as local recurrence when excised completely was not observed. Given metastatic potential of malignant AME, multimodal therapy may be warranted., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: BRCA1/BRCA2 mutation carriers indefinitely comprise a distinct group of patients with breast cancer (BC), with their tumors displaying specific pathologic characteristics. Although these connections are known, they are not fully elucidated. We therefore sought to investigate the clinicopathologic characteristics and overall survival of Greek patients with BC carrying BRCA1/BRCA2 mutations., Patients and Methods: Greek patients with BC diagnosed between 1999 and 2016, fulfilling the National Comprehensive Cancer Network criteria for genetic testing, were analyzed for BRCA1/BRCA2 mutations by Sanger sequencing or by a 94-gene panel. Medical records and pathology reports were retrospectively reviewed to retrieve patient and tumor baseline characteristics. Potential associations with mutation status were assessed using the Fisher exact, Pearson χ 2 , and Mann-Whitney tests., Results: Of 2096 selected patients with BC, we identified 297 (14.2%) BRCA1 and 88 (4.2%) BRCA2 carriers. The mean age at BC diagnosis was 40 and 42.6 years, respectively (P = .02). Tumor histologic subtypes in BRCA1 and BRCA2 carriers were predominantly ductal (79%) followed by medullary (10%), and ductal (72%) followed by lobular (15%), respectively. A significantly higher percentage of BRCA2 tumors were human epidermal growth factor receptor 2-positive, compared with BRCA1 tumors (21.7% vs. 5.8%; P < .001). Second primary cancer diagnosis was more frequent in BRCA1 compared with BRCA2 mutation carriers (36.2% vs. 10.7%; P < .001), whereas there was no difference in 15-year overall survival (hazard ratio, 0.92; 95% confidence interval, 0.48-1.83; P = .804) between the 2 groups., Conclusions: These data confirm established observations in the pathology of BRCA-related tumors and provide further insight on the association of rare histologic entities with mutations in these genes, which can be clinically beneficial., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Mucinous carcinoma (MC) of the breast is a rare and special type of malignancy, with a substantial amount of extracellular mucin. We compared the clinicopathological features and the long-term survival of MC patients with those of invasive ductal carcinoma-no special type (IDC-NST) patients, and we examined prognostic factors of MC. A total of 116 patients with mucinous carcinoma and 3,258 patients with IDC-NST who underwent surgery at our hospital (1977-2008) were enrolled. The 10-year overall survival rate and breast cancer-specific survival rate (BSS) of the MC patients (88.3%, 93.7%) were both significantly higher than those of IDC-NST patients (81.6%, 85.0%) (p=0.015, p=0.005, respectively). A Cox regression analysis demonstrated that MC tended to be an independent prognostic factor (hazard ratio 0.44, p=0.098). The BSS of the MC patients with positive lymph node (LN) metastasis was significantly poorer than that of the patients without it, by univariate analysis (p=0.002). The tumor size in the MC patients with positive LN metastasis (mean 3.2 cm) was significantly larger than that in the patients without it (mean 1.9 cm) (p=0.0004). Although a Cox regression analysis revealed no independent factor, MC patients with positive LN metastasis should be treated for advanced invasive ductal breast cancer., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Despite data demonstrating the safety of omitting axillary surgery in older women with early-stage breast cancer, the incidence of axillary surgery remains high. It was hypothesized that the prevalence of nodal positivity would decrease with advancing age., Methods: The National Cancer Data Base was used to construct a cohort of adult women with early-stage, clinically node-negative, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative breast cancer treated between 2013 and 2015. Multivariable logistic regression was used to assess the relationship between age and nodal positivity, and this was stratified by the axillary surgery category. Modified Poisson regression was used to estimate the proportion of women receiving adjuvant therapy according to age and nodal status., Results: The incidence of axillary surgery among women aged 70 and older (n = 51,917) remained high nationwide (86%). There was a significant decrease in nodal positivity with advancing age in women with early-stage, ER+, clinically node-negative breast cancer from the youngest cohort up to patients aged 70 to 89 years, and this was independent of histologic subtype (ductal vs lobular), race, comorbidities, and socioeconomic factors. Overall, less than 10% of women aged 70 or older who underwent surgery had node-positive disease, regardless of axillary surgery type, and almost 95% of node-positive patients aged 70 or older were at pathological stage N1mi or N1., Conclusions: Axillary surgery may be safely omitted for many older women with ER+, clinically node-negative, early-stage breast cancer. Nodal positivity declines with advancing age, and this suggests varied biology in older patients versus younger patients., (© 2019 American Cancer Society.)

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.

Background: Metastatic regional lymph nodes (LN) is a strong predictor of worse long-term outcome. Therefore, different LN staging systems have been proposed in recent years. In this study, we proposed a modified lymph node ratio (mLNR) as a new lymph node staging system and then compared the prognostic performance of mLNR with American Joint Committee on Cancer N stage, lymph node ratio (LNR) and log odds of metastatic lymph nodes in breast cancer patients., Methods: Breast cancer patients who underwent surgery between 2004 and 2012 were identified from the Surveillance, Epidemiology, and End Results database. Restricted cubic spline functions were calculated to characterize the association between variables and the risk of death. The Cox proportional hazards models were constructed to assess the predictive ability of different lymph node staging systems using the Akaike's Information Criterion (AIC) and Harrell's concordance index (C-index)., Results: A total of 264,096 breast cancer patients were enrolled and 187,785 (71.1%) patients had a limited number of LNs harvested. In the limited LN harvest cohort, the prognostic performance of LNR decreased and mLNR could greatly solve this problem. In addition, among the entire cohort, mLNR modeled as a continuous value had the best predictive ability (AIC: 922021.9 and C-index: 0.727) than other lymph node staging systems., Conclusions: The predictive ability of LNR is restricted by a limited LN harvest. However, mLNR shows superiority to LNR and other lymph node staging systems especially in a limited LN harvest cohort, making mLNR the most powerful lymph node staging systems., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Flat epithelial atypia (FEA) is an alteration of terminal duct lobular units by a proliferation of ductal epithelium with low-grade atypia. No consensus exists on whether the diagnosis of FEA in core needle biopsy (CNB) requires excision (EXC). We retrospectively identified all in-house CNBs obtained between January 2012 and July 2018 with FEA. We reviewed all CNB slides and assessed radiologic-pathologic concordance. An upgrade was defined as invasive carcinoma (IC) and/or ductal carcinoma in situ in the EXC. The EXC slides of all upgraded cases were rereviewed. Out of ∼15,700 consecutive CNBs in the study period, 106 CNBs from 106 patients yielded FEA alone or with classic lobular neoplasia (LN). We excluded 52 CNBs (40 patients with prior/concurrent carcinoma and 12 without EXC). After rereview, we reclassified 14 cases (2 marked nuclear atypia, 10 focal atypical ductal hyperplasia, 2 benign). The final FEA study cohort consisted of 40 CNBs from 40 women. The CNB targeted mammographic calcifications in 36 (90%) cases, magnetic resonance imaging nonmass enhancement in 3 (8%), and 1 (2%) sonographic mass. All CNBs were deemed radiologic-pathologic concordant. FEA was present alone in 34 CNBs and with LN in 6. EXC yielded 2 low-grade IC, each spanning <2 mm, identified in tissue sections without biopsy site changes. The remaining 38 cases had no upgrade. Classic LN did not affect the upgrade. The upgrade rate of FEA was 5%; both minute, low-grade "incidental" IC. We conclude that nonsurgical management may be considered in patients without prior/concurrent carcinoma and radiologic-pathologic concordant CNB diagnosis of FEA.

Objectives: Triple negative breast cancer (TNBC) is a heterogenous disease and associated with unfavorable outcomes. The role of sonographic features and its association with disease outcome in TNBC is uncertain. Our study aimed to determine the prognosis predictive value of sonographic features in TNBC., Methods: Women with TNBC patients treated between January 2009 and December 2015 were retrospectively included. Patients' clinic-pathological, sonographic features, recurrence-free survival (RFS), and breast cancer-specific survival (BCSS) events were reviewed and analyzed. Kaplan-Meier analysis and multivariable Cox regression were used to determine the prognostic factors in TNBC., Results: A total of 433 TNBC patients were included. With a median follow-up of 4.8 years, 58 (13.4%) RFS and 35(8.1%) BCSS events were detected. Besides lymphatic vascular invasion (LVI), nuclear grade III, tumor >2.0 cm, and positive axillary lymph node (ALN), multivariable analysis found that vertical orientation in ultrasound imaging was independently associated with worse RFS (Hazard Ratio (HR) = 3.238; 95% Confidential Interval (CI), 1.661-6.312; P = 0.001) and BCSS (HR = 7.028; 95% CI, 3.199-15.436; P < 0.001). TNBC with vertical orientation in ultrasound imaging had higher ALN metastasis burden than those with sonographic parallel features (2.7 ± 1.0 vs 1.5 ± 0.2, P = 0.003)., Conclusions: TNBC presenting with vertical orientation in ultrasound imaging was associated with worse disease outcome and a greater number of ALN metastasis., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC., Methods: The National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS., Results: Altogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p < 0.001). The greater observed OS for patients with TNBC persisted when controlling for stage and when comparing propensity score matched cohorts. On Cox regression, lower age, T1 status, N0 status, chemotherapy, TNBC disease, and radiation therapy (RT) were associated with improved OS., Conclusions: MBC had an association with poorer OS compared to TNBC, while RT and chemotherapy receipt were associated with improved OS for patients regardless of stage. Further studies are needed to corroborate the conclusions herein., Competing Interests: Declaration of competing interest The authors have no conflicts of interest. There was no funding for this study. Ethical approval was not required for the present manuscript., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There is no consensus on the ideal time interval between the completion of neo-adjuvant chemotherapy (NAC) and definitive surgery for patients with breast cancer. This study sought to determine the ideal time interval from completion of systemic therapy to surgery in an attempt to define a best practice. A retrospective analysis of all patients undergoing NAC for Stage I-III breast cancer from 1998-2010 was undertaken. Analysis of all demographic and clinical information was performed, with emphasis on interval from completion of systemic therapy to definitive surgical management. Three hundred and eighty eight patients met the inclusion criteria with a median age of 50 (61.9% white, 33.8% black and 4.3% other). Overall, 2.8% of patients were Stage I, 57.2% Stage II and 40% Stage III. Median follow-up was 85 months. Pathologic response to systemic therapy was complete in 20.6%, partial in 67.8% and no response or progression in 11.6%; responders (pCR or pPR) were noted to have significantly improved Disease free survival (DFS) and Overall survival (OS). Patients undergoing surgical intervention 4-6 weeks after completion of NAC were noted to have a trend towards improved DFS and OS on multivariable analysis. These findings were also observed in the nonlinear relationship between survival risk and surgery time window using martingale residual plots. Timing of surgical intervention following the receipt of NAC may not appear to affect DFS or OS., (© 2019 Wiley Periodicals, Inc.)

Background: HER2-targeted neoadjuvant therapy has high efficacy in treating HER2-positive breast cancer. Response to neoadjuvant therapy helps clinicians make treatment decisions and make estimates about prognosis. This study examined clinicopathologic features to determine which may be most predictive of response to neoadjuvant therapy in HER2 + breast cancer., Patients and Methods: Patients with HER2 + breast cancer (n = 173) who had an initial biopsy performed between 2010 and 2016 were identified at our institution. Tumor response was evaluated on excisional specimens using the MD Anderson residual cancer burden (RCB) classification. Tumors with pathologic complete response (defined as no residual invasive carcinoma in the breast and lymph nodes) and RCB-I were classified as having response and tumors with RCB-II and -III as having no response. Patient age, tumor size, nuclear grade (1/2 vs. 3), mitosis, Nottingham grade, HER2 immunohistochemistry (1/2+ vs. 3+), HER2/CEP17 (chromosome enumeration probe 17) ratio, HER2 copy number, estrogen receptor, progesterone receptor, Ki-67, and tumor-infiltrating lymphocytes (TIL) were evaluated and correlated with response. TILs were evaluated for an average and also for the hot spot/total tumor stromal ratio., Results: Small tumor size, low estrogen receptor and progesterone receptor expression, HER2 immunohistochemistry 3+, high Ki-67, high HER2/CEP17 ratio, and high HER2 copy number were significantly associated with response (all P < .05). TIL hot spot was associated with RCB in univariate (P < .05) but not multivariate analyses., Conclusion: Clinicopathologic features may help predict HER2 + breast cancer response to neoadjuvant therapy. Larger studies would be useful to confirm these associations, which may have relevance to clinical practice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear., Methods: We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples., Results: Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1-19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02)., Conclusions: Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.

Introduction: Microglandular adenosis (MGA) is a rare benign proliferative lesion lacking a myoepithelial cell layer; 27% of all reported cases have progressed to invasive carcinoma. Salivary gland-type carcinomas of the breast are also uncommon, representing 2% of all breast cancers. This wide spectrum of neoplasms tends to be triple negative and generally has an excellent prognosis. Given the rarity of salivary gland-type carcinomas of the breast arising from MGA, there are few reports of these cases in literature. As such, there is uncertainty regarding their diagnosis and treatment strategies., Presentation of Case: We report the rare case of a 66-year-old woman who presented with a triple negative, invasive carcinoma with salivary gland-type features, arising from MGA. The patient underwent mastectomy with sentinel lymph node biopsy, followed by Taxotere and Cyclophosphamide (TC) chemotherapy and 50 Gy in 25 fractions of radiation to her chest wall. We reviewed the available literature on salivary gland-type breast carcinomas arising from MGA., Discussion: Despite the generally unfavourable characteristics associated with carcinoma arising in microglandular adenosis (MGACA), most patients with MGACA have favourable outcomes., Conclusions: The findings of the present case and reviewed cases are consistent with the literature on MGA, atypical MGA (AMGA), and MGACA. Future study of this rare entity is warranted to establish a consensus surrounding its clinical significance and treatment methods., Competing Interests: Declaration of Competing Interest KJJ has served as a consultant for Esai, Genomic Health Inc, Novartis, Purdue Pharma, Pfizer and Roche. She received research support from Astra Zeneca Eli Lilly, and was a speaker for Apobiologix, Novartis, as well as Purdue Pharma. The remaining authors declare that there is no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: In the present study, we present a large institutional study to determine the influence of age≥ 80 years on breast cancer presentation and prognosis., Methods: The study is a retrospective analysis of our prospectively maintained breast cancer database study using data from of women managed from January 2007 through December 2013. Clinicopathologic characteristics were correlated with outcomes according to age (<80 years and ≥ 80 years)., Results: During the study period, 2083 women with invasive breast cancer were included of which 160 women aged ≥ 80 years (7.7 %). Overall survival was lower in the oldest old than in younger counterparts (p < 0.0001) as was distant metastasis free survival (p = 0.004). Differences in management included more radical surgeries and less chemotherapy and radiotherapy in case of age≥ 80 years. By multivariate analysis, age ≥ 80 years was an independent predictive factor of poor overall survival., Conclusion: In the present study, age ≥ 80 years was an independent predictive factor of poor overall survival., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: To investigate whether androgen receptor (AR) status affects neoadjuvant chemotherapy (NACT) in stage II and III Turkish breast cancer patients., Methods: The histological response for breast and axilla was assessed according to the Miller-Payne grading system. In light microscopy, nuclear staining in tumor cells was evaluated, and nuclear staining above 1% was accepted as positive for AR expression. The patients were divided into 3 groups according to the intensity of AR staining: low, moderate, and high., Results: In total, 71 women with breast cancer were included in the study. In univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER-2) status were tested to determine which of these factors were associated with >90% responsiveness. AR negativity was found to be the only statistically significant factor. In multivariate analysis, AR positivity at each intensity was found to be the single important factor affecting decreasing pathologic response in patients receiving NACT for breast cancer., Conclusion: Our results show that AR positivity is associated with poor response to NACT in Turkish breast cancer patients and that AR positivity is independent of stage, hormone receptor status, HER-2 status, and disease stage., (© 2020 S. Karger AG, Basel.)

A 58-year-old female patient presented with left breast lump. Mammography and ultrasonography were performed, which reported lesions suspicious of malignancy in the left breast and axilla. Core biopsy of the lesions revealed invasive ductal carcinoma with axillary lymph node metastasis. Staging CT scan (thorax, abdomen and pelvis) identified a coexisting neoplasm in the ascending colon. Colonoscopy was performed and the tumour in the ascending colon was biopsied. Histopathological examination revealed adenocarcinoma. In the multidisciplinary team cancer meeting, it was decided to treat the breast cancer first and then the colon cancer, followed by adjuvant chemotherapy. In the first operation, left modified radical mastectomy was performed. Two weeks after her initial operation, the patient underwent laparoscopic right hemicolectomy. Postoperatively, the patient did not develop any complications and was referred to oncology for chemotherapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Data regarding axillary management after neoadjuvant endocrine therapy (NET) are lacking. This study examined axillary management of hormone receptor-positive (HR+) patients based on initial treatment with NET, neoadjuvant chemotherapy (NAC), or upfront surgery., Methods: Patients with stage 2 or 3 HR+/HER2- breast cancer treated between 2012 and 2015 were identified in the National Cancer Database. The study examined axillary surgery [sentinel lymph node biopsy (SLNB), SLNB followed by axillary lymph node dissection (ALND), or upfront ALND] by initial treatment stratified by cN0/N1 using pairwise comparisons and multivariable logistic regression., Results: Of 92,204 eligible patients, 2138 (2.3%) received NET, 11,014 (12%) received NAC, and 79,052 (85.7%) received surgery. Among 60,998 cN0 patients, attempted SLNB was more likely for surgery patients (86.2%, 47,159/54,684) and NET patients (85.8%, 1342/1564) than for NAC patients (79.9%, 3793/4750) (both p < 0.001). Among 31,206 cN1 patients, attempted SLNB was more likely for the surgery patients (46.0%, 11,201/24,368) than for the NET patients (41.8%, 240/574; p = 0.05) or the NAC patients (39.8%, 2491/6264; p < 0.0001). The differences between surgery and NET did not persist in the adjusted analyses. Among both the cN0 patients (n = 13,856) and the cN1 patients (n = 8688) with pN1 disease shown by SLNB, the NET patients were treated with ALND less frequently than those receiving NAC or surgery (p < 0.0001 for all comparisons). In the multivariate analysis, for the patients with pN1 disease shown by SLNB, NET use was associated with increased odds of undergoing SLNB alone [cN0 patients: odds ratio (OR), 1.31, 95% confidence interval (CI), 1.04-1.64; cN1 patients: OR 1.45; 95% CI 1.00-2.10]., Conclusions: For stages 2 and 3 HR+/HER2- patients, SLNB use after NET was similar to that for upfront surgery. Among those with pN1 disease, the NET patients were less likely to undergo ALND. Additional outcomes data are needed to guide axillary management after NET.

Background: The impact of locoregional radiotherapy (RT) after neoadjuvant chemotherapy (NACT) and mastectomy in breast cancer patients is currently unclear. Several publications have suggested that patients with a favorable response to NACT might not benefit from RT after mastectomy., Methods: A retrospective analysis of three prospective randomized NACT trials was performed. Information on the use of RT was available for 817 breast cancer patients with non-inflammatory breast cancer who underwent mastectomy after NACT within the GeparTrio, GeparQuattro, and GeparQuinto-trials. RT was administered to 676 of these patients (82.7%)., Results: The 5-year cumulative incidence of locoregional recurrence (LRR) was 15.2% (95% confidence interval [CI] 9.0-22.8%) in patients treated without RT and 11.3% in patients treated with RT (95% CI 8.7-14.3%). In the multivariate analysis, RT was associated with a lower risk of LRR (hazard ratio 0.51, 95% CI 0.27-1.0; p = 0.05). This effect was shown especially in patients with cT3/4 tumors, as well as in patients who were cN+ before neoadjuvant therapy, including those who converted to ypN0 after neoadjuvant therapy. In the bivariate analysis, disease-free survival was significantly worse in patients who received RT, however this was not confirmed in the multivariate analysis., Conclusions: Our results suggest that RT reduces the LRR rates in breast cancer patients who receive a mastectomy after NACT without an improvement in DFS. Prospective randomized controlled trials such as the National Surgical Adjuvant Breast and Bowel Project B-51/RTOG 1304 trial will analyze whether RT has any benefit in patients who have a favorable response after NACT.

Background: Residual axillary lymph node involvement after neoadjuvant systemic therapy (NST) is the determining factor for postmastectomy radiation therapy (PMRT). Preoperative identification of patients needing PMRT is essential to enable shared decision-making when choosing the optimal timing of breast reconstruction. We determined the risk of positive sentinel lymph node (SLN) after NST in clinically node-negative (cN0) breast cancer., Methods: All cT1-3N0 patients treated with NST followed by mastectomy and SLNB between 2010 and 2016 were identified from the Netherlands Cancer Registry. Rate of positive SLN for different breast cancer subtypes was determined. Logistic regression analysis was performed to determine correlated clinicopathological variables with positive SLN., Results: In total 788 patients were included, of whom 25.0% (197/788) had positive SLN. cT1-3N0 ER+HER2+, cT1-3N0 ER-HER2+ , and cT1-2N0 triple-negative patients had the lowest rate of positive SLN: 7.2-11.5%, 0-6.3%, and 2.9-6.2%, respectively. cT1-3N0 ER+HER2- and cT3N0 triple-negative patients had the highest rate of positive SLN: 23.8-41.7% and 30.4%, respectively. Multivariable regression analysis showed that cT2 (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.01-3.96), cT3 (OR 2.56; 95% CI 1.30-5.38), grade 3 (OR 0.44; 95% CI 0.21-0.91), and ER+HER2- subtype (OR 3.94; 95% CI 1.77-8.74) were correlated with positive SLN., Conclusions: In cT1-3N0 ER+HER2+, cT1-3N0 ER-HER2+, and cT1-2N0 triple-negative patients treated with NST, immediate reconstruction can be considered an acceptable option due to low risk of positive SLN. In cT1-3N0 ER+HER2- and cT3N0 triple-negative patients treated with NST, risks and benefits of immediate reconstruction should be discussed with patients due to the relatively high risk of positive SLN.

Radiation recall dermatitis is an acute inflammatory reaction that occurs on previously irradiated skin by usage of chemotherapeutic agents and other triggering drugs. The recall reaction is usually associated with drugs but may also occur following ultraviolet radiation. We report a patient with radiation recall dermatitis, triggered after imaging procedures that involved radiation., (© 2019 The Australasian College of Dermatologists.)

Purpose: The detection rate of breast ductal carcinoma in situ (DCIS) has increased significantly, raising the concern that DCIS is overdiagnosed and overtreated. Therefore, there is an unmet clinical need to better predict the risk of progression among DCIS patients. Our hypothesis is that by combining molecular signatures with clinicopathologic features, we can elucidate the biology of breast cancer progression, and risk-stratify patients with DCIS., Methods: Targeted exon sequencing with a custom panel of 223 genes/regions was performed for 125 DCIS cases. Among them, 60 were from cases having concurrent or subsequent invasive breast cancer (IBC) (DCIS + IBC group), and 65 from cases with no IBC development over a median follow-up of 13 years (DCIS-only group). Copy number alterations in chromosome 1q32, 8q24, and 11q13 were analyzed using fluorescence in situ hybridization (FISH). Multivariable logistic regression models were fit to the outcome of DCIS progression to IBC as functions of demographic and clinical features., Results: We observed recurrent variants of known IBC-related mutations, and the most commonly mutated genes in DCIS were PIK3CA (34.4%) and TP53 (18.4%). There was an inverse association between PIK3CA kinase domain mutations and progression (Odds Ratio [OR] 10.2, p < 0.05). Copy number variations in 1q32 and 8q24 were associated with progression (OR 9.3 and 46, respectively; both p < 0.05)., Conclusions: PIK3CA kinase domain mutations and the absence of copy number gains in DCIS are protective against progression to IBC. These results may guide efforts to distinguish low-risk from high-risk DCIS.

Objective: To determine the outcome of sonographically-guided indigenous low-cost metallic clip placement for tumour localisation in patients of early breast cancer undergoing neoadjuvant chemotherapy. ., Methods: The prospective analytical study was conducted at the Institute of Nuclear Medicine and Oncology, Lahore, Pakistan, from May 2016 to December 2017, and comprised biopsy-proven breast cancer cases. Under sonographic guidance, metallic clips were placed as markers within the lesions before their scheduled preoperative neoadjuvant chemotherapy. The procedure was performed using an 18 gauge lumbar puncture needle and 25 gauge needle by a locally devised simple and cost-effective technique. Post-procedure mammography was performed to confirm the location of clips within the lesions and to evaluate its role in imaging assessment of treatment response after neo adjuvant chemotherapy. SPSS 20 was used for data analysis., Results: There were 30 women with a mean age of 40.43+11.35 years (range: 21-60 years). These women had 32 lesions with a mean size of 26.72+9.85mm (range: 8-58mm). Breast conserving surgery was performed on 28(87.5%) lesions and negative margins were achieved in all these cases. Modified radical mastectomy was performed on 4(12/5%) non-responding lesions. No complication was noted in association with metallic clip placement, and the clips were easily visualised on mammograms without causing any interference with treatment response., Conclusions: Sonographically-guided metallic clip placement by a simple indigenously devised technique before neoadjuvant chemotherapy was found to be a well-tolerated, safe and cost-effective method for accurate preoperative localisation of tumour bed and to assess response to therapy.

Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is a lack of literature on alteration of biomarkers in metastatic breast cancer (MBC) at progression. We included 32 patients of upfront MBC. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu documented at baseline and at progression. Median age was 46 (range 26-72) years. Estrogen receptor altered in 6 (18.75%) patients [4 (12.5%) positive to negative and 2 (6.25%) from negative to positive], progesterone receptor altered in 8 (25.3%) patients (6 [18.75%] positive to negative and 2 [6.25%] negative to positive) and human epidermal growth factor receptor 2/neu altered in 5 (15.6%) patients (all were positive to negative). Therapy was changed as per new receptor status. Documentation of change in receptor status may be justified to determine further therapy and prognosis in MBC at progression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Yes-associated protein (YAP) protein acts as tumorigenic factor in many solid tumors, but the situation in breast cancer is under debate. Here, we would analyze its status in breast cancer. YAP expression in the 110 primary breast cancer and their paired local recurrent tumors was investigated. Clinicopathologic data for age, histologic grading, hormone status, lymph nodes and HER2 status were also gathered and analyzed. 46.4% (51/110) primary breast cancer tissues were positive for total YAP expression which was significantly higher than that in the recurrent tissues (10.9%; P < 0.05). The expression of total YAP protein in the primary breast cancer tissues was positively associated with the tumor size, especially in triple negative breast cancer (TNBC) subtype (P < 0.05). Higher total or nuclear YAP expression in the primary tumor was correlated with poor disease-free survival among patients with TNBC (P < 0.05). In the multivariate models, nuclear YAP expression was an independently prognostic factor in TNBC. High total or nuclear YAP expression predicts poor prognosis among patients with TNBC. It might be a therapeutic target for TNBC in the future., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ductal carcinoma in situ (DCIS) with microinvasion (DCISM) can be challenging in balancing the risks of overtreatment versus undertreatment. We compared DCISM, pure DCIS, and small volume (T1a) invasive ductal carcinoma (IDC) as related to histopathology, treatment patterns, and survival outcomes., Methods: Women ages 18-90 years who underwent breast surgery for DCIS, DCISM, or T1a IDC were selected from the SEER Database (2004-2015). Multivariate logistic regression and Cox proportional hazards models were used to estimate the association of diagnosis with treatment and survival, respectively., Results: A total of 134,569 women were identified: 3.2% DCISM, 70.9% DCIS, and 25.9% with T1a IDC. Compared with invasive disease, DCISM was less likely to be ER+ or PR+ and more likely to be HER2+. After adjustment, DCIS and invasive patients were less likely to undergo mastectomy than DCISM patients (DCIS: OR 0.53, 95% CI 0.49-0.56; invasive: OR 0.86, CI 0.81-0.92). For those undergoing lumpectomy, the likelihood of receiving radiation was similar for DCISM and invasive patients but lower for DCIS patients (OR 0.57, CI 0.52-0.63). After adjustment, breast-cancer-specific survival was significantly different between DCISM and the other two groups (DCIS: HR 0.59, CI 0.43-0.8; invasive: HR 1.43, CI 1.04-1.96). However, overall survival was not significantly different between DCISM and invasive disease, whereas patients with DCIS had improved OS (HR 0.83, CI 0.75-0.93)., Conclusions: Although DCISM is a distinct entity, current treatment patterns and prognosis are comparable to those with small volume IDC. These findings may help providers counsel patients and determine appropriate treatment plans.

Each year, more than 250,000 women in the United States are diagnosed with invasive breast cancer. Although overall mortality for breast cancer patients has declined, it is still the second most common cause of cancer death in women. This article provides an overview of nonmetastatic breast cancer in women, including general features, diagnostic considerations, and treatments for the most common breast cancer subtypes.

Background: We aimed to analyze the association between Paget's disease (PD) and breast cancer (BC) subtypes and compare the effect of breast-conserving surgery (BCS) as a local treatment with mastectomy for PD., Materials and Methods: Data of patients with histologic type International Classification of Diseases-0-3 8540-8543 who were treated from 1973 to 2014 were retrieved from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. A chi-square test was used to identify differences in categorical data among different groups. Overall survival (OS) was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, sequential landmark analysis, and propensity score-matched analysis., Results: The study cohort included 5398 patients. Triple-negative BC accounted for the fewest patients with PD-only (1/22, 4.54%), Paget's disease-ductal carcinoma in situ (PD-DCIS) (3/48, 6.25%), and Paget's disease-invading ductal carcinoma (PD-IDC) (23/352, 6.53%). According to the results of the log-rank test and Cox analysis, the 10-year OS rates were similar for the BCS and mastectomy subgroups among patients with PD-DCIS or PD-IDC. Furthermore, there were no significant differences in survival benefits among the different surgeries after propensity score matching. Landmark analyses for OS of patients with PD-DCIS or PD-IDC surviving more than 1, 3, and 5 y showed no significant differences in survival. There were statistical differences in 10-year OS rates for patients with PD-DCIS or PD-IDC who underwent radiation therapy, or not, following BCS (both, P < 0.001)., Conclusions: For patients with PD-DCIS or PD-IDC, breast conservation therapy with lumpectomy and radiation is an effective local treatment strategy, compared with mastectomy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Breast cancer occurs in about 1% of men, but the number of men receiving a diagnosis is increasing. Data on male breast cancer (MBC) is limited, and treatment for men is based primarily on treatments used for women. However, some argue that breast cancer in men is a different disease than breast cancer in women. Multiple risk factors, including those with genetic and environmental origins, affect the likelihood of men receiving a breast cancer diagnosis. This article discusses types of MBC, risk factors, treatment options, and ethical concerns men encounter after they receive a breast cancer diagnosis., (© 2019 American Society of Radiologic Technologists.)

Male breast cancer is a rare disease and it differs from breast cancer in women by some characteristics. The incidence of the disease has increased in the last 25 years. The records of male patients who underwent surgery for breast cancer between 2007 and 2017 were retrospectively reviewed in a tertiary care hospital in Istanbul, Turkey. The patients' ages, background, family history, clinical features, histopathological features of the tumour, its stage, the treatment and the survival were investigated. SPSS 15.0 for Windows programme was used for statistical analysis.Survival analysis was performed with Kaplan-Meier method.Determinants were analysed by univariate Cox regression analysis. A total of 15 patients were evaluated in our study. Fourteen patients had invasive ductal carcinoma and one patient had intraductal papillary carcinoma. The median followup period of the patients was 36 months The axillary lymph node metastasis positivity rate (number of metastatic lymph nodes/number of lymph nodes dissected) was statistically significantly higher in patients who died than in patients who survived.In univariate Cox regression analysis, the effects of age, tumour size, estrogen, progesterone, the presence of HER2/neu receptor and axillary metastasis on survival were not determined. We believe that raising awareness on male breast cancer in the community, genetic testing and screening mammography in high-risk patients will be useful in early diagnosis of the disease and improvement of its prognosis.