Abstract PO4-08-10: Genetic mutations and associated rates of pathologic complete response among a diverse patient population with early stage triple negative breast cancer
Authors: Taylor Caitlin , Sheen Melanie , Cattie Rabia , Chung Victoria , Bratton Melyssa , Lakey Meredith , Biggs Erin 
Published: May 2024

Abstract
Background:
Combination treatment with chemotherapy and immunotherapy remains the standard of care for high risk, early-stage triple negative breast cancer (TNBC). Although the addition of immunotherapy improves rates of pathologic complete response (pCR) and event-free survival, approximately 50% of patients achieve pCR with neoadjuvant chemotherapy alone suggesting that some patients may safely avoid the potential toxicities of immunotherapy without compromising outcomes.1,2 Markers of immune activation including PD-L1 expression and tumor infiltrating lymphocytes have demonstrated prognostic significance; however, identifying a predictive biomarker to aid in selecting those patients most likely to benefit from immunotherapy remains an unmet need.3,4 Genetic mutations are suggestive of DNA susceptibility to damage and the role they may play as a potential marker of immune response is unclear.5,6 This study explores genetic analysis and mutation rates among a diverse cohort of patients with TNBC to identify patterns associated with and without pCR.
Methods:
We evaluated 105 women diagnosed with Stage I-III TNBC and treated with combination neoadjuvant chemotherapy and immunotherapy at Ochsner Cancer Center between December 2019 through June 2022. Exclusion criteria included ER+, PR+, HER2+, or unknown receptor status, no pembrolizumab in the neoadjuvant setting, no definitive surgery following neoadjuvant treatment, absence of documented race and age less than 18 years of age. Data was collected utilizing Epic Slicer Dicer program, in addition to chart review. Genetic analysis was performed using a variety of DNA-based next generation sequencing analysis platforms.
Results:
91 patients met inclusion criteria. 17 patients were found to have pathogenic mutations (BRCA1/2, POLE and ATM), 38 patients had variants of undetermined significance (VUS) and 36 patients had neither. Among patients with pathogenic genetic mutations, 81.25% had a pCR following neoadjuvant treatment compared to 58.33% of those with a VUS and 47.06% of those with no known mutation (p=0.07). Before adjusting for age and stage, patients with a pathogenic mutation were 73% more likely to achieve pCR than those with no known genetic mutations (crude RR: 1.73, 95% CI: 1.13-2.65). After adjusting for age and stage, the relationship was not statistically significant (aRR: 1.15, 95% CI: 0.78-1.34). Among the 47 Black patients, 5 were found to have a pathogenic mutation and 29 had a VUS. 11 of the 39 White patients were found to have a pathogenic mutation while only 6 had a VUS. Across all genetic mutation categories, Black patients experienced lower rates of pCR than White patients. White patients with a known pathogenic mutation had the highest rate of pCR at 90.91%, while Black patients with no identified mutation had the lowest rate of pCR at 38.46%. The generalizability of these results may be limited due to small sample size.
Conclusion:
Our results demonstrating higher rates of genetic variants among patients achieving pCR regardless of race highlight the importance of better understanding how these variants correlate with tumor mutational burden (TMB) and further, the role this may play in predicting immune-response. Larger studies are needed to assess TMB as a predictive biomarker in early-stage TNBC as this may provide opportunities to further individualize treatment and minimize toxicity among this group of patients. Additionally, given differences in the prevalence of pathogenic mutations and VUS among Black patients, better understanding the relationship between mutation status and immune response is imperative to optimize outcomes in this high-risk population.
Table.
Citation Format: Caitlin Taylor, Melanie Sheen, Rabia Cattie, Victoria Chung, Melyssa Bratton, Meredith Lakey, Erin Biggs. Genetic mutations and associated rates of pathologic complete response among a diverse patient population with early stage triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-10.