Rachel Greenup

BACKGROUND: Men represent a small proportion of breast cancer diagnoses, and they are often excluded from clinical trials. Current treatments are largely extrapolated from evidence in women. We compare practice patterns between men and women with breast cancer following the publication of several landmark clinical trials in surgery. PATIENTS AND METHODS: Patients with invasive breast cancer (2004-2015) from the National Cancer Data Base were identified; subcohorts were created based on eligibility for NSABP-B06, CALGB 9343, and ACOSOG Z0011. Practice patterns were stratified by gender and compared. Cox proportional hazards regression analyses were utilized to estimate the association between OS and gender. RESULTS: Of the 1,664,746 patients identified, 99% were women and 1% were men. Among NSABP-B06 eligible men, mastectomy rates did not change (consistently ~ 80%), and their adjusted OS was minimally worse compared with women (HR 1.19, 95% CI 1.11-1.28). Following publication of CALGB 9343, omission of radiation after lumpectomy was less likely in men and lagged behind that of women, despite similar OS (male HR 0.92, 95% CI 0.59-1.44). Application of ACOSOG Z0011 findings resulted in deescalation of axillary surgery for men and women with comparable OS (male HR 0.69, 95% CI 0.33-1.45). CONCLUSIONS: Uptake of clinical trial results for men with breast cancer often mirrors that for women, despite exclusion from these studies. Furthermore, when study findings were applied to eligible patients, men and women demonstrated similar survival. Observational studies can help inform the potential application of study findings to this unique population and improve patient enrollment in clinical trials.

PURPOSE: Contralateral prophylactic mastectomy (CPM) is increasingly performed in average-risk patients despite the lack of survival benefit. In an era of heightened awareness of healthcare costs, we sought to determine the impact of CPM on financial toxicity in breast cancer. METHODS: A single-institution propensity-matched analysis of female patients who underwent unilateral mastectomy (UM) with or without CPM for breast cancer over an 18-month period. Patients with a history of genetic predisposition or bilateral cancer were excluded. The validated Comprehensive Score for financial Toxicity (COST) evaluated financial toxicity among participants. Multivariable regression analysis evaluated the relationship between CPM and financial toxicity. Relevant domains of the Breast Q and SF12 instruments were examined as secondary outcomes. Sensitivity analysis was performed using propensity-weighting to examine robustness of results and increase our sample size. RESULTS: Overall, 104 patients were identified, equally distributed across UM and CPM. CPM was not associated with financial toxicity, as evidenced by comparable COST scores (adjusted difference, 1.53 [- 3.24 to 6.29]). Minor complications were significantly lower in UM patients (UM, 8%; CPM, 31%). CPM was associated with significantly higher Breast Q psychosocial well-being score (adjusted difference, 10.58 [1.34 to 19.83]). BREAST Q surgeon satisfaction, SF12 mental and physical component scores were comparable. Similar results were noted on sensitivity analysis involving 194 patients. CONCLUSIONS: Choice for CPM was associated with higher minor complications, but led to improved psychosocial well-being without a higher degree of patient-reported financial toxicity. Prospective studies are needed to discern the influence of CPM on the incidence and trajectory of financial toxicity.

Use of genomic assays to determine distant recurrence risk in patients with early stage breast cancer has expanded and is now included in the American Joint Committee on Cancer staging manual. Algorithmic alternatives using standard clinical and pathology information may provide equivalent benefit in settings where genomic tests, such as OncotypeDx, are unavailable. We developed an artificial neural network (ANN) model to nonlinearly estimate risk of distant cancer recurrence. In addition to clinical and pathological variables, we enhanced our model using intraoperatively determined global mammographic breast density (MBD) and local breast density (LBD). LBD was measured with optical spectral imaging capable of sensing regional concentrations of tissue constituents. A cohort of 56 ER+ patients with an OncotypeDx score was evaluated. We demonstrated that combining MBD/LBD measurements with clinical and pathological variables improves distant recurrence risk prediction accuracy, with high correlation (r = 0.98) to the OncotypeDx recurrence score.

PURPOSE: While various studies have highlighted the prognostic significance of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAT), the impact of additional adjuvant therapy after pCR is not known. EXPERIMENTAL DESIGN: PubMed was searched for studies with NAT for breast cancer and individual patient-level data was extracted for analysis using plot digitizer software. HRs, with 95% probability intervals (PI), measuring the association between pCR and overall survival (OS) or event-free survival (EFS), were estimated using Bayesian piece-wise exponential proportional hazards hierarchical models including pCR as predictor. RESULTS: Overall, 52 of 3,209 publications met inclusion criteria, totaling 27,895 patients. Patients with a pCR after NAT had significantly better EFS (HR = 0.31; 95% PI, 0.24-0.39), particularly for triple-negative (HR = 0.18; 95% PI, 0.10-0.31) and HER2+ (HR = 0.32; 95% PI, 0.21-0.47) disease. Similarly, pCR after NAT was also associated with improved survival (HR = 0.22; 95% PI, 0.15-0.30). The association of pCR with improved EFS was similar among patients who received subsequent adjuvant chemotherapy (HR = 0.36; 95% PI, 0.19-0.67) and those without adjuvant chemotherapy (HR = 0.36; 95% PI, 0.27-0.54), with no significant difference between the two groups (P = 0.60). CONCLUSIONS: Achieving pCR following NAT is associated with significantly better EFS and OS, particularly for triple-negative and HER2+ breast cancer. The similar outcomes with or without adjuvant chemotherapy in patients who attain pCR likely reflects tumor biology and systemic clearance of micrometastatic disease, highlighting the potential of escalation/deescalation strategies in the adjuvant setting based on neoadjuvant response.See related commentary by Esserman, p. 2771.

BACKGROUND: Elderly women with clinically node-positive (cN+) breast cancer (BC) often have comorbidities that limit life expectancy and complicate treatment. We sought to determine whether the number of lymph nodes (LNs) retrieved among older women with node-positive BC was associated with overall survival (OS). METHODS: Using the National Cancer Database (2010-2015), women 70-90 y with cN + BC and ≥1 LNs removed were categorized by treatment sequence: upfront surgery or neoadjuvant chemotherapy (NAC). Multivariable Cox proportional hazards models with restricted cubic splines characterized the functional association of LN retrieval with OS; threshold values of LN retrieval were estimated. Cox proportional hazards models were used to estimate the association of LN retrieval groups with OS. RESULTS: In the upfront surgery cohort, a nonlinear association was identified between LNs retrieved and OS. In the NAC cohort, no association was identified. For the upfront surgery cohort, the optimal threshold value of LN retrieval was 21 LNs (90% confidence interval 18-23). Based on this estimate, LN retrieval groups were created: <6, 6-11, 12-17, 18-23, and >23 LNs. After adjustment, retrieval of <12 LNs in the upfront surgery group was associated with a worse OS. No differences were observed in the NAC group. CONCLUSIONS: For elderly women receiving upfront surgery, there is no survival benefit to removing more than 12 LNs, and for those receiving NAC, there is no association between number of LNs removed and survival. In older women who present with cN + BC, aggressive surgery to remove more than 12 LNs may not be necessary.