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Purpose: Despite delays between diagnosis and surgery adversely affecting survival, patients frequently transfer their breast cancer care between institutions. This study was performed to assess the prevalence and effect of such transfers of care (TsOC) on the time to surgery, and its impact on current time-dependent breast cancer quality metrics at Commission on Cancer (CoC) and National Accreditation Program for Breast Centers (NAPBC)-accredited institutions., Methods: Patients having non-metastatic invasive breast cancer diagnosed between 2006 and 2015 at CoC and NAPBC centers ("reporting facilities") in the National Cancer Database were reviewed. TsOC refer to transferring into or out of a reporting facility between diagnosis and surgery., Results: Among 622,793 patients, 36.6% of patients transferred care. TsOC add 7.3, 7.8, 8.7, and 9.8 days in time to surgery, chemotherapy, radiotherapy, and endocrine therapy, respectively (p's < 0.0001). On multivariable analysis, the odds of surgery occurring > 90 days from diagnosis were greatest for patients undergoing unilateral or bilateral mastectomy, Black or Hispanic patients, and those having TsOC (ORs > 1.73, p's < 0.0001). TsOC increase the odds of non-compliance, per patient, for chemotherapy, radiotherapy and endocrine therapy time-dependent measures by 65.4%, 25.6%, and 56.5%, respectively (p < 0.0001)., Conclusions: TsOC for newly diagnosed breast cancers to or from an accredited facility result in delays in time to surgery which can affect compliance with time-dependent quality measures. Facilities frequently receiving transferred patients may be most adversely affected. Although non-compliance with these quality measures is low, institutions and accrediting bodies should be aware of these associations in order to comply with time-dependent standards.

Nipple-sparing mastectomy (NSM) provides a cosmetic and psychological benefit for patients, but concerns on nipple involvement (NI) of tumor continue to persist. Several studies have reported factors for predicting NI, but the results were inconsistent and uncomprehensive, making patient selection difficult. The aim of the systematic review was to pool the published data to further discern factors associated with NI. A literature review was conducted of PubMed database, following the PRISMA guidelines. Relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effect or fix-effect model. Publication bias and Chi-square test were also calculated. From 1978 to 2014, 27 clinical studies with 7971 patients met the inclusion criteria. Predictive factors suggest higher rates of NI including the following: tumor-to-nipple distance (TND) ≤ 2.5 cm (3.65, 1.42-9.33); positive lymph node status (2.09, 1.71-2.57); stage III or IV disease (2.41, 1.93-3.00); tumor size > 5 cm (2.42, 1.95-3.02); estrogen receptor (ER)-negative status (1.19, 1.01-1.40); progesterone receptor (PR)-negative status (1.52, 1.25-1.84); HER-positive status (1.76, 1.46-2.12); patients with ductal carcinoma in situ (DCIS) compared with invasive ductal carcinoma (1.55, 1.16-2.08). Due to the statistical heterogeneity detected with certain parameters, further investigations to confirm their association with NI will be needed. Patients with one or more risk factors such as centrally located tumors; higher tumor stage; large tumors; ER-negative/PR-negative/HER-positive status and associated DCIS have higher risk of NI. Taking these factors into consideration comprehensively may help with decision-making process for NSM.

South Asians from India and Pakistan represent one of the fastest growing immigrant populations in the US, yet there are limited data assessing breast cancers for this distinct ethnic sub-group. The aim of this study was to analyze clinical-pathologic, treatment and outcome characteristics of U.S.-residing Indian-Pakistani (IP) versus non-Hispanic white (NHW) female breast cancer patients to assess if any differences/disparities exist. The study cohort consisted of 2,393 IP and 555,832 NHW women (diagnosed 1988-2006) in the SEER database. Differences between the two populations were analyzed using chi-squared and multivariate regression analysis. Age-adjusted incidence, mortality, and relative survival rates were calculated for the two groups. Significant differences in the characteristics of the IP cohort's invasive disease included: younger median age at presentation; larger tumor size; higher stage, higher grade, more involved lymph-nodes, and more hormone receptor negative disease (all P < 0.01). The age-adjusted incidence and breast cancer mortality were lower in IP women. The relative survival at 5 years was statistically significant at 84% for IP versus 89% for NHW women, but was not significantly different on multivariate analysis (P > 0.05). Within each stage (Tis, I, II), there were no disparities in the rate of breast conservation surgery (BCS) or in the percentage of patients receiving adjuvant radiation after BCS for the 2 cohorts. Post-mastectomy radiation was delivered significantly more often in stage I/II IP patients undergoing mastectomy. In conclusion, this analysis suggests that while there appear to be significant differences in the features of breast cancers of US-residing IP women, no disparities were noted in the rates of breast conserving surgery or adjuvant radiation, as seen in some other ethnicities. The more aggressive clinical-pathologic features stage-for-stage in IP women may partially explain the more frequent use of post-mastectomy RT in this patient population. These findings warrant further investigation.

The mediator of DNA damage checkpoint protein 1 (MDC1) regulates cell cycle checkpoints and recruits repair proteins to sites of double-stranded DNA damage using its BRCA1 carboxy-terminal (BRCT) domains. MDC1 under-expression has been associated with radiosensitivity in cells. The purpose of this study was to evaluate the clinico-pathologic and prognostic significance of MDC1 expression in a cohort of early-stage breast cancer patients treated with breast conservation therapy. Paraffin specimens from 489 women with early-stage breast cancer treated with breast conservation therapy were constructed into tissue microarrays. The arrays were stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and MDC1. This was correlated with clinico-pathologic factors and outcomes. MDC1 expression was evaluable in 351 cases (72%). Decreased MDC1 expression was found to be correlated with nodal failure (P = 0.05), but not ipsilateral breast relapse-free survival (IBRFS), distant metastasis-free survival (DMFS), or overall survival (OS). Subset analysis in node-negative patients revealed that decreased MDC1 expression predicted for nodal failure (P < 0.01). Our study is the first to assess the clinico-pathologic and prognostic significance of MDC1 expression in patients with early-stage breast cancer treated with lumpectomy and radiotherapy. MDC1 under-expression predicted for nodal failure, but not for IBRFS, DM, or OS. The role of other proteins involved in the DNA damage repair pathway and their effects on MDC1 expression, as well as the level of MDC1 expression in patients with BRCA1 mutations warrant further investigation.

Women with BRCA1 and BRCA2 mutations have an elevated risk of breast cancer and ovarian cancer, but also of developing second primary breast cancer. BRCA1/2 mutation carriers with breast cancer must choose between breast conservation (BCT) and mastectomy (M) yet data on outcomes are limited. The purpose of this study is to compare long-term outcome following BCT and M in BRCA1/2 carriers. 655 women with BRCA1/2 mutations diagnosed with breast cancer and treated with BCT (n = 302) or M (n = 353) were identified and underwent follow-up to assess local, regional, and systemic recurrence. Local failure as first failure was significantly more likely in those treated with BCT compared to M, with a cumulative estimated risk of 23.5 vs. 5.5%, respectively, at 15 years (P < 0.0001); 15-year estimates in carriers treated with BCT and chemotherapy was 11.9% (P = 0.08 when compared to M). Most events appeared to be second primary cancers rather than failure to control the primary tumor. The risk of contralateral breast cancer was high in all groups, exceeding 40%, but was not statistically significantly different by use of adjuvant radiotherapy (RT) or not, suggesting no added risk from scatter RT at 10 and 15 years. There were no differences seen in regional or systemic recurrences between the BCT and M groups, and no difference in overall survival. In conclusion, BRCA1/2 mutation carriers with breast cancer have similar survival whether treated with M or BCT. However, women undergoing BCT have an elevated risk of a second in-breast event that is significantly reduced in the presence of chemotherapy. Contralateral breast cancer events are very common.

Background: This study was undertaken to evaluate the prognostic significance of Bcl-2, a apoptosis-related protein, in patients with early stage breast cancer treated with breast conservation treatment (BCT)., Methods: After obtaining IRB approval, 504 patients with early stage breast cancer treated with BCT were entered in this study. The paraffin specimens were constructed into tissue micro-arrays with two-fold redundancy, processed and stained for Bcl-2 antibody. Bcl-2 expression was correlated with other clinicopathological parameters and clinical outcomes., Results: Bcl-2 expression was identified in 116 cases (28%). Bcl-2 expression was positively correlated with both estrogen receptor and progesterone receptor status (P < 0.0001, respectively). Bcl-2 expression was associated with ipsilateral breast tumor recurrence (P = 0.0322, by log-rank test). Multivariate analysis using Cox proportional hazard model showed that Bcl-2 expression still retained significance as an independent prognostic factor for breast recurrence (P = 0.0348)., Conclusions: Bcl-2 expression is highly associated with an increased risk of local recurrence in patients with early stage breast cancer. Immunohistochemical staining of the primary tumor for Bcl-2 might be useful to select optimal treatment options for these patients.