Predicting pathological response in early-stage triple-negative breast cancer: Exploring the role of BRCA gene mutations—A retrospective single-institution study.

Abstract

e12656 Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, constituting approximately 15-20% of all breast cancer cases. While less than 10% of all breast cancer patients harbor BRCA1/2 mutations, ~20% of TNBC patients carry these mutations. Notably, at least one-third of BRCA1 carriers develop TNBC. This study aimed to investigate the association between BRCA mutation status and pathological response (PR) in early-stage TNBC patients, specifically, the impact of BRCA positivity on achieving pathological complete response (pCR), and identify other potential predictors of PR. Methods: We conducted a retrospective cohort study of patients with early-stage (Stage I-III) triple-negative breast cancer diagnosed and treated at our institution between January 2012 and June 2022, following Institutional Review Board (IRB) approval. Patients were identified from our Institutional Cancer Registry based on complete data availability (including other inclusion criteria) excluding patients who did not receive neoadjuvant chemotherapy. Data on demographics, tumor characteristics, treatment regimens, and pathological response (assessed according to [specified criteria]) were extracted from the charts. Results: Out of 228 patients diagnosed with early-stage triple-negative breast cancer, 54.6% had no genetic mutations, while 7.9%, 4.9%, and 8.4% harbored BRCA1, BRCA2, and other mutations, respectively. Notably, 23.4% did not receive genetic counseling or testing at our institution. Patients with BRCA2 mutations had a 100% pathological response rate, of which 57.14% had pCR, compared to 85.7% for BRCA1, of which 71.43% had pCR. Furthermore, 93.8% of patients with other genetic mutations had pathological response, of which 56.25% had pCR, as compared to 68.42% in non-mutated cases of which 26.7% had pCR ( P=0.038). Analysis of other variables revealed no significant impact of age, BMI, performance status, or neoadjuvant chemotherapy regimen on pathological response. Conclusions: This retrospective study suggests a trend towards higher complete pathological responses in early-stage triple-negative breast cancer patients with BRCA and other genetic mutations compared to those without. These findings were statistically significant, indicating a potential clinical trend that specific genetic mutations may be associated with improved response to neoadjuvant chemotherapy in early-stage triple-negative breast cancer. Further research is needed to confirm these findings and guide the development of personalized treatment strategies based on a patient's genetic profile. Additionally, our findings highlight the importance of genetic testing for all patients with early-stage triple-negative breast cancer, regardless of age or family history.