BRCA1 and BRCA2 play a central role in DNA repair and their germline pathogenic variants (gBRCA) confer a high risk for developing breast and ovarian cancer. Standard chemotherapy regimens for these cancers include DNA-damaging agents. We hypothesized that gBRCA carriers might be at higher risk of developing chemotherapy-related hematologic toxicity and therapy-related myeloid neoplasms (t-MN). We conducted a retrospective study of women newly diagnosed with invasive breast or ovarian cancer who were screened for gBRCA1/gBRCA2 at Geneva University Hospitals. All patients were treated with (neo-)adjuvant chemotherapy. We evaluated acute hematologic toxicities by analyzing the occurrence of febrile neutropenia and severe neutropenia (grade 4) at day 7–14 of the first cycle of chemotherapy and G-CSF use during the entire chemotherapy regimen. Characteristics of t-MN were collected. We reviewed medical records from 447 patients: 58 gBRCA1 and 40 gBRCA2 carriers and 349 non-carriers. gBRCA1 carriers were at higher risk of developing severe neutropenia (32% vs. 14.5%, p = 0.007; OR = 3.3, 95% CI [1.6-7], p = 0.001) and of requiring G-CSF for secondary prophylaxis (58.3% vs. 38.2%, p = 0.011; OR = 2.5, 95% CI [1.4–4.8], p = 0.004). gBRCA2 carriers did not show increased acute hematologic toxicities. t-MN were observed in 2 patients (1 gBRCA1 and one non-carrier). Our results suggested an increased acute hematologic toxicity upon exposure to chemotherapy for breast and ovarian cancer among gBRCA1 but not gBRCA2 carriers. A deeper characterization of t-MN is warranted with the recent development of PARP inhibitors in frontline therapy in gBRCA breast and ovarian cancer.

BRCA1 和 BRCA2 在 DNA 修复中起着核心作用，它们的种系致病变异 (g BRCA ) 赋予患乳腺癌和卵巢癌的高风险。这些癌症的标准化疗方案包括 DNA 损伤剂。我们假设gBRCA携带者发生化疗相关血液学毒性和治疗相关髓系肿瘤 (t-MN) 的风险可能更高。我们对新诊断患有浸润性乳腺癌或卵巢癌并接受gBRCA1/gBRCA2筛查的女性进行了一项回顾性研究在日内瓦大学医院。所有患者均接受（新）辅助化疗。我们通过分析第一个化疗周期第 7-14 天发热性中性粒细胞减少症和严重中性粒细胞减少症（4 级）的发生率以及整个化疗方案期间使用 G-CSF 来评估急性血液学毒性。收集了 t-MN 的特征。我们审查了 447 名患者的医疗记录：58 g BRCA1和 40 gBRCA2 携带者以及 349 名非携带者。gBRCA1携带者发生严重中性粒细胞减少症的风险更高（32% 对 14.5%，p  = 0.007；OR = 3.3，95% CI [1.6-7]，p  = 0.001）并且需要 G-CSF 进行二级预防 (58.3 % 对比 38.2%，p  = 0.011；OR = 2.5，95% CI [1.4–4.8]，p = 0.004）。gBRCA2携带者没有表现出增加的急性血液学毒性。在 2 名患者（1 名gBRCA1和一名非携带者）中观察到 t-MN 。我们的结果表明，在gBRCA1而不是gBRCA2携带者中，暴露于乳腺癌和卵巢癌化疗后急性血液学毒性增加。随着 PARP 抑制剂在gBRCA乳腺癌和卵巢癌一线治疗中的最新发展，有必要对 t-MN 进行更深入的表征。