Evaluation of Complete Pathological Regression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients with BRCA1 Founder Mutation Aided Bayesian A/B Testing Approach

The aim of this study was to evaluate the probability of pathologic complete regression (pCR) by the BRCA1 gene mutation status in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy. The study involved 143 women (mean age 55.4 ± 13.1 years) with TNBC. The BRCA1 mutation was observed in 17% of the subjects. The most commonly used (85.3%) chemotherapy regimen was four cycles of adriamycine and cyclophosphamide followed by 12 cycles of paclitaxel (4AC + 12T). The differences between clinico-pathological factors by BRCA1 status were estimated. Odds ratios and 95% confidence intervals for pCR vs. non-pCR were calculated using logistic regression. The probability distribution of pCR based on BRCA1 status was estimated using beta distributions. The presence of T3–T4 tumours, cancer in stages II and III, lymphovascular invasion, and the use of chemotherapy schedules other than 4AC + 12T significantly decreased the odds of pCR. It was established that there was a 20% chance that pCR in patients with the BRCA1 mutation was 50% or more times as frequent than in patients without the mutation. Thus, the BRCA1 mutation can be a predictive factor for pCR in patients with TNBC.

Response to Neoadjuvant Systemic Therapy for Breast Cancer in BRCA Mutation Carriers and Noncarriers: A Single-Institution Experience

Purpose To compare the pathologic complete response (pCR) rate and relapse-free survival (RFS) and overall survival (OS) after neoadjuvant systemic chemotherapy (NST) in patients with breast cancer with and without deleterious BRCA1 and BRCA2 mutations. Patients and Methods A total of 317 women who underwent BRCA genetic testing and were treated with NST for breast cancer between 1997 and 2009 were included in the study. The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models were fit to determine the associations between BRCA status, pCR, and survival. Results Fifty-seven (18%) and 23 (7%) patients had BRCA1 and BRCA2 mutations, respectively. Twenty-six (46%) of 57 BRCA1 carriers achieved a pCR, compared with three (13%) of 23 BRCA2 carriers and 53 (22%) of 237 BRCA noncarriers (P < .001). In the multivariate logistic model, BRCA1 status (odds ratio [OR] = 3.16; 95% CI, 1.55 to 6.42; P = .002), estrogen receptor (ER) negativity (OR = 1.96; 95% CI:1.05 to 3.65; P = .03) and concurrent trastuzumab use (OR = 4.18; 95% CI, 2.04 to 8.57; P < .001) remained as independent significant predictors for a pCR. At a median follow-up of 3.2 years, 69 patients (22%) experienced a disease recurrence or death. No significant differences were noted in survival outcomes with respect to BRCA status and type of NST received. However, among BRCA1 carriers, patients who achieved a pCR had better 5-year RFS (P = .001) and OS (P = .01) rates than patients who did not. Conclusion BRCA1 status and ER negativity are independently associated with higher pCR rates in patients with breast cancer. Overall prognosis of breast cancer in BRCA carriers is similar to sporadic breast cancers.