Neoadjuvant Chemotherapy Response and Genetic Susceptibility in Recently Parous Women with Breast Cancer: A Retrospective Analysis

Background: Women with recent parity are at increased short-term breast cancer (BC) risk and face a worse prognosis. The effect of parity on response to neoadjuvant chemotherapy (NAC) is unstudied, and the influence of inherited susceptibility on parity-related short-term risk remains unclear. Methods: A retrospective case-cohort study analyzed women age 50 years or younger with non-metastatic BC diagnosed between 2010 and 2020 who underwent genetic testing and were treated at Northwestern Medicine. Associations between NAC response and recency of parity were evaluated using multivariate logistic regression, stratified by tumor biologic subtypes. Relationships between germline mutations, recency of parity, and BC were explored via multi-state modeling and linear regression. Results: Among 1080 eligible women, 231 received NAC. Treatment response was poorer in parous women with triple-negative tumors than in nullipara women regardless of the recency of parity (P < 0.03). Among 122 women (11.3%) with detectable pathogenic mutations, adjusted analyses with both modeling approaches showed no indications that BRCA1/2 carriers had a greater hazard of a BC diagnosis in the decade after recent parity than nulliparous mutation carriers. For BRCA2 and PALB2 carriers, BC diagnosis occurred less frequently in the postpartum intervals. Conclusion: This study showed a poor response to NAC in parous triple-negative BC (TNBC) patients than in nullipara patients. The effects of immunotherapy-based regimens deserve evaluation in the context of parity. Postpartum BC occurrence is not increased in BRCA1/2 carriers. The effects of rarer susceptibility genes may differ. These important effects of parity on BC in young women and those at genetic risk warrant larger prospective studies.