Department of Oncology, Hôpitaux Universitaires de Genève, 4 Rue Gabrielle Perret-Gentil, 1205, Geneva, Switzerland.
Department of Genetic Medicine, Laboratory and Clinical Pathology, Hôpitaux Universitaires de Genève, 4 Rue Gabrielle Perret-Gentil, 1205, Geneva, Switzerland.
Breast Cancer Res Treat. 2019 Apr;174(3):775-783. doi: 10.1007/s10549-018-05127-2. Epub 2019 Jan 11.
BRCA1 and BRCA2 proteins are central to DNA repair process through homologous recombination. We hypothesize that BRCA1/BRCA2 mutation carriers may exhibit increased hematological toxicity when receiving genotoxic chemotherapy.
We included women with primary breast cancers screened for BRCA1/BRCA2 germline mutations and treated with (neo)adjuvant chemotherapy in Geneva (Swiss cohort). The primary endpoint was the incidence of febrile neutropenia following the first chemotherapy cycle (C1). Secondary endpoints were the incidence of grade 3-4 neutropenia, grade 4 neutropenia and hospitalization during C1, G-CSF use and chemotherapy dose reduction during the entire chemotherapy regimen. Long-term toxicities (hematological, cardiac and neuropathy) were assessed in the Swiss cohort and a second cohort of patients from Lyon (French cohort).
Overall, 221 patients were assessed for acute hematological toxicity, including 23 BRCA1 and 22 BRCA2 carriers. Following the C1, febrile neutropenia had an incidence of 35% (p = 0.002), 14% (p = 0.562) and 10% among BRCA1, BRCA2 and non-carriers, respectively. Grade 4 neutropenia was found in 57% of BRCA1 (p < 0.001), 14% of BRCA2 (p = 0.861) and 18% of non-carriers. G-CSF support was necessary in 86% of BRCA1 (p = 0.005), 64% of BRCA2 (p = 0.285) and 51% of non-carriers. For long-term toxicity analysis, 898 patients were included (167 BRCA1-, 91 BRCA2- and 640 non-carriers). There was no difference between the 3 groups.
BRCA1 germline mutations is associated with greater acute hematological toxicity in breast cancer patients. These observations could have implication for primary prophylaxis with G-CSF.
BRCA1 和 BRCA2 蛋白是同源重组过程中 DNA 修复的核心。我们假设，携带 BRCA1/BRCA2 突变的患者在接受致瘤化疗时可能会出现更高的血液学毒性。
我们纳入了在日内瓦（瑞士队列）接受（新）辅助化疗的筛查 BRCA1/BRCA2 种系突变的原发性乳腺癌女性患者。主要终点是第一个化疗周期（C1）后发热性中性粒细胞减少症的发生率。次要终点是 3-4 级中性粒细胞减少症、4 级中性粒细胞减少症和 C1 期间住院、G-CSF 使用和整个化疗方案期间化疗剂量减少的发生率。瑞士队列和里昂（法国队列）的另一批患者评估了长期毒性（血液学、心脏和神经病变）。
总体而言，对 221 例急性血液学毒性患者进行了评估，包括 23 例 BRCA1 和 22 例 BRCA2 携带者。C1 后，发热性中性粒细胞减少症的发生率分别为 35%（p=0.002）、14%（p=0.562）和 10%，BRCA1、BRCA2 和非携带者。4 级中性粒细胞减少症在 BRCA1 中为 57%（p<0.001），BRCA2 中为 14%（p=0.861），非携带者中为 18%。BRCA1 中 86%（p=0.005）、BRCA2 中 64%（p=0.285）和非携带者中 51%需要 G-CSF 支持。对于长期毒性分析，纳入了 898 例患者（167 例 BRCA1-、91 例 BRCA2-和 640 例非携带者）。三组之间没有差异。
BRCA1 种系突变与乳腺癌患者更严重的急性血液学毒性相关。这些观察结果可能对 G-CSF 的一级预防具有重要意义。
