Dennis Saya, Tsukioki Takahiro, Kocherginsky Masha, Qi Andrea Keya, DeHorn Sarah, Gurley Michael, Wrubel Erica, Luo Yuan, Khan Seema Ahsan
Division of Biostatistics and Informatics, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Breast and Thyroid Surgery, Okayama University Hospital, Okayama, Japan.
Ann Surg Oncol. 2025 Apr 9. doi: 10.1245/s10434-025-17204-0.
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.
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.
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.
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.
近期生育过的女性短期患乳腺癌（BC）的风险增加，且预后较差。生育对新辅助化疗（NAC）反应的影响尚未得到研究，遗传易感性对与生育相关的短期风险的影响仍不清楚。
一项回顾性病例队列研究分析了2010年至2020年间在西北大学医学院接受基因检测并接受治疗的50岁及以下非转移性BC女性。使用多变量逻辑回归评估NAC反应与生育近期情况之间的关联，并按肿瘤生物学亚型分层。通过多状态建模和线性回归探索种系突变、生育近期情况和BC之间的关系。
在1080名符合条件的女性中，231名接受了NAC。无论生育近期情况如何，三阴性肿瘤的经产妇的治疗反应均比未生育女性差（P < 0.03）。在122名（11.3%）可检测到致病突变的女性中，两种建模方法的调整分析均未表明BRCA1/2携带者在近期生育后的十年内患BC的风险比未生育的突变携带者更高。对于BRCA2和PALB2携带者，产后期间BC诊断的发生率较低。
本研究表明，与未生育患者相比，经产妇三阴性乳腺癌（TNBC）患者对NAC的反应较差。基于免疫疗法的方案的效果值得在生育背景下进行评估。BRCA1/2携带者产后患BC的情况并未增加。罕见易感基因的影响可能有所不同。生育对年轻女性和有遗传风险的女性BC的这些重要影响值得进行更大规模的前瞻性研究。
