Faculty Bibliography

BACKGROUND:Oncologic outcomes with nipple-sparing mastectomy (NSM) continue to be established. We examine oncologic trends, outcomes, and risk factors, including tumor-to-nipple distance (TND), in therapeutic NSMs. METHODS:Demographics, outcomes, and overall trends for all NSMs undertaken for a therapeutic indication from 2006 to 2017 were analyzed. Oncologic outcomes were investigated with specific focus on recurrence and associated factors, including TND. RESULTS:A total of 496 therapeutic NSMs were performed with average follow-up time of 48.25 months. The most common tumor types were invasive carcinoma (52.4%) and ductal carcinoma in situ (50.4%). Sentinel lymph node sampling was performed in 79.8% of NSMs; 4.1% had positive frozen sentinel lymph node biopsies while 15.7% had positive nodal status on permanent pathologic examination. The most common pathologic cancer stage was stage IA (42.5%) followed by Stage 0 (31.3%).Per NSM, the rate of local recurrence was 1.6% (N=8); the rate of regional recurrence was 0.6% (N=3). In all, 171 NSMs had magnetic resonance imaging available to assess tumor-to-nipple distance (TND). NSMs with TND ≤1 centimeter (25.0% versus 2.4%, p=0.0031/p=0.1129) and ≤2 centimeters (8.7% versus 2.0%; p=0.0218/p=0.1345) trended to higher rates of locoregional recurrence. In univariate analysis, TND ≤1 centimeter was the only significant risk factor for recurrence (OR=13.5833, p=0.0385). No factors were significant in regression analysis. CONCLUSIONS:In this group of early stage and in situ breast carcinoma, therapeutic NSM appears oncologically safe with a locoregional recurrence rate of 2.0%. Tumor-to-nipple distances of ≤1 centimeter and ≤2 centimeters trended to higher rates of recurrence.

Background/Objective: Growing evidence suggests that tumor immune-microenvironment influences breast cancer carcinogenesis and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer correlates with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcinoma in situ (DCIS) is less understood.
Method(s): Our institutional database was queried for pure DCIS from 2010-2018 (n=668). Local recurrences (n=13) were matched 1:4 to patients without recurrence. TILs were evaluated by the International TILs Working Group Guidelines. Percentage of TILs was assessed from the densest focus in 1 high-power field of stroma touching the basement membrane. Statistical methods included cluster analyses, logistic, and Cox regression models.
Result(s): Sixty-nine patients, including the 13 recurrences were evaluated. Fifty-four (78%) were treated by breast-conserving surgery (BCS). The median follow-up was 6.7 years. TILs were defined as sparse (<45%) and dense (>=45%). Dense TILs was associated with younger age (p=0.045), larger tumor size (p<0.001), high nuclear grade (p<0.001), comedo histology (p=0.016), necrosis (p=0.038), and recurrence (p=0.001). Nine patients with dense TILs had a mean time to recurrence of 74 months compared to 4 patients with sparse TILs who had a mean time to recurrence of 93 months (p=0.044) (Figure).
Conclusion(s): We found that dense TILs in DCIS was significantly associated with age, tumor size, grade, and histology. Most importantly, dense TILs are a significant predictor of recurrence in patients with DCIS, which underlies the prognostic importance of the immune microenvironment of early breast cancers. (Figure Presented)

PURPOSE/OBJECTIVE:Genomic assays, or tissue gene profiling tests, are widely used to predict recurrence of early stage invasive breast cancer and guide systemic therapy. The purpose of our study was to examine the current national trends of genomic testing in male breast cancer (MBC) and its association with systemic therapy. MATERIALS AND METHODS/METHODS:The National Cancer Database (NCDB) includes 6227 cases of pathologic T1/T2 and N0/N1 MBC from 2008 to 2014 with known genomic testing status. Results of the tests were grouped as low, intermediate, and high risk of recurrence scores (RRS). Statistical analysis included multivariate logistic regression and Chi-square tests. A supplemental analysis in female breast cancer was provided as reference. RESULTS:Of the 6227 cases of MBC age 18-90, 1478 (23.74%) underwent genomic testing. Testing was significantly associated with age, race, tumor grade, year of diagnosis, receptor status, and nodal status. Distribution of RRS in MBC was 59.3% low, 27.4% intermediate, and 13.3% high. RRS in men were significantly associated with tumor grade and size, but not nodal status. Those with a low RRS were 7-times more likely to be treated with hormone therapy alone (AOR 7.18, CI 5.78-8.91, P < 0.001). Those with a high RRS were five times more likely to receive a combination of hormone and chemotherapy (AOR 5.16, CI 3.60-7.40, P < 0.001). CONCLUSION/CONCLUSIONS:Rates of testing and distribution of RRS in men and women with early stage invasive breast cancer are similar. Treatment patterns in MBC varied significantly based on genomic testing results, even when adjusted for other clinicopathologic features. Further investigation is required to determine the prognostic and predictive nature of genomic testing in male breast cancer.

BACKGROUND:The treatment of ductal carcinoma in situ (DCIS) remains controversial and may be particularly difficult for patients with minimal disease. There is a dearth of information regarding patients who have been diagnosed with DCIS on core needle biopsy (CNB), who have no residual disease in the lumpectomy specimen. The purpose of this study was to explore the frequency of this presentation and short-term outcomes in these patients. METHODS:Our institutional Breast Cancer Database was queried for all women who were diagnosed with pure DCIS from 2010 to 2016 and treated with lumpectomy. Variables included patient and tumor characteristics, adjuvant treatment, and ipsilateral breast tumor recurrence (IBTR). Statistical analyses included Pearson's chi-square, Fisher's exact tests, and Kaplan-Meier analysis. RESULTS:Of 547 patients with pure DCIS, 50 (14%) had DCIS on CNB only. Of the patients with DCIS on CNB only, 15 were treated with lumpectomy and radiation therapy (RT), while 35 underwent lumpectomy without RT. At a median follow-up of 4 years, there were 3 (6%) IBTR all within the same quadrant as the original lumpectomy site. None of the patients who recurred received adjuvant RT or hormonal therapy. CONCLUSIONS:Despite the minimal extent of disease exhibited in these cases, 6% of patients with DCIS on CNB only had IBTR at a median follow-up of 4 years. These data suggest that even minimal DCIS represents a significant risk of recurrence to the patient. Size and margins are not sufficient criteria to stratify risk and guide decisions for adjuvant therapies.

BACKGROUND:Recent data support the use of post-mastectomy radiation therapy (PMRT) in women with one to three positive lymph nodes; however, the benefit of PMRT in patients with micrometastatic nodal disease (N1mi) is unknown. We evaluated the survival impact of PMRT in patients with N1mi within the National Cancer Database. METHODS:The pattern of care and survival benefit of PMRT was examined in women with pT1-2N1mi breast cancer who underwent mastectomy without neoadjuvant chemotherapy. Univariable and multivariable Cox proportional hazard models were employed for survival analysis, and subanalyses of high-risk patients and a propensity score-matched (PSM) cohort were completed. RESULTS:From 2004 to 2014, we identified 14,019 patients who fitted the study criteria. PMRT was delivered in 18.5% of patients and its use increased over the study period. Patients treated with PMRT were younger, had better performance status and larger primaries, were estrogen receptor (ER)-negative, had higher grade, lymphovascular invasion and positive surgical margins, and more often received systemic therapy. PMRT was significantly associated with overall survival (OS) in univariable analysis (hazard ratio [HR] 0.75 [0.64-0.89]), but was not significant in multivariable analysis (adjusted HR 1.01 [0.84-1.20]). There was no survival benefit to PMRT in ER-negative, high-grade, and/or young patients. There were 2 (0.9%) death events in the sentinel lymph node biopsy (SLNB) + PMRT group versus 21 (2.9%) in the SLNB-alone group (log-rank p = 0.053), and 8 (3.9%) death events in the axillary lymph node biopsy (ALNB) + PMRT group versus 27 (3.6%) in the axillary lymph node dissection-alone group (p = 0.82). There was no significant association between PMRT and OS within the PSM subgroup. CONCLUSION/CONCLUSIONS:In this largest reported retrospective study, no OS differences were associated with PMRT, which suggests that PMRT may not benefit every patient with microscopic nodal disease.