German Breast Group, Neu-Isenburg, Germany.
Medical Clinic II, University Hospital Frankfurt, Germany.
Eur J Cancer. 2021 Mar;145:44-52. doi: 10.1016/j.ejca.2020.12.007. Epub 2021 Jan 7.
BRCA1 and BRCA2 play a central role in DNA repair. Therefore, patients harbouring germline (g) BRCA1/2 mutations (m) treated with chemotherapy might be at higher risk of haematological toxicities.
Patients from German Breast Group (GBG) and Arbeitsgemeinschaft Gynäkologische Onkologie-breast group studies with early triple-negative breast cancer (TNBC) and known gBRCA1/2m status treated with anthracycline-taxane-based neoadjuvant chemotherapy were analysed. Primary objective was the rate of neutropenia grade (G)III-IV in cycle 1 (C1). Secondary objectives included effects on overall and other haematological toxicities GIII-IV in C1, cumulative haematological toxicity across all cycles, relative total dose intensity, and granulocyte-colony stimulating factor prophylaxis. Haematological toxicities under taxanes, carboplatin, and cyclophosphamide were explored.
Two hundred nine of 1171 (17.8%) evaluated patients had gBRCA1/2m. In C1, 37.4% gBRCA1/2m versus 35.7% wild-type patients had neutropenia GIII-IV (P = 0.683). For C1, gBRCA1/2m predicted neither for neutropenia GIII-IV (odds ratio [OR]: 1.26, 95% confidence intervals [CI]: 0.87-1.82, P = 0.226) nor for other haematological toxicities GIII-IV (OR: 0.91, 95% CI: 0.64-1.31, P = 0.625) in multivariable regression models. Analyses of cumulative toxicities across all cycles yielded similar results except thrombocytopaenia GIII-IV, which was increased in gBRCA1m patients. In patients treated with taxanes, the rate of haematological toxicities GIII-IV was higher in gBRCA1/2m compared with wild-type (59.5% versus 43.1%; p < 0.001). No difference was seen under cyclophosphamide or platinum-containing chemotherapies.
gBRCA1/2m was not associated with higher risk of overall severe haematological toxicities in the first cycle or cumulatively across all cycles under standard chemotherapy for TNBC. Under taxane, patients with gBRCA1/2m might have a higher risk of haematological toxicities GIII-IV, requiring further research.
BRCA1 和 BRCA2 在 DNA 修复中发挥核心作用。因此，接受化疗的携带胚系 (g) BRCA1/2 突变 (m) 的患者可能有更高的血液学毒性风险。
分析了德国乳腺组 (GBG) 和妇科肿瘤学工作组 (AG-Breast) 早期三阴性乳腺癌 (TNBC) 研究中接受蒽环类药物-紫杉烷类新辅助化疗且已知 gBRCA1/2m 状态的患者。主要目标是第 1 周期 (C1) 中性粒细胞减少症 G3-4 发生率。次要目标包括 C1 中总体和其他血液学毒性 G3-4 的影响、所有周期的累积血液学毒性、相对总剂量强度和粒细胞集落刺激因子预防。探索了紫杉烷类、卡铂和环磷酰胺下的血液学毒性。
在 1171 例评估患者中，有 209 例 (17.8%) 携带 gBRCA1/2m。在 C1 中，gBRCA1/2m 患者中性粒细胞减少症 G3-4 发生率为 37.4%，野生型患者为 35.7%（P=0.683）。对于 C1，gBRCA1/2m 既不能预测中性粒细胞减少症 G3-4（比值比 [OR]：1.26，95%置信区间 [CI]：0.87-1.82，P=0.226），也不能预测其他血液学毒性 G3-4（OR：0.91，95% CI：0.64-1.31，P=0.625）。所有周期累积毒性分析结果相似，除 gBRCA1m 患者血小板减少症 G3-4 发生率增加外。在接受紫杉烷类治疗的患者中，gBRCA1/2m 患者血液学毒性 G3-4 发生率高于野生型（59.5%比 43.1%；p<0.001）。在环磷酰胺或含铂化疗中未见差异。
在标准 TNBC 化疗中，gBRCA1/2m 与第 1 周期或所有周期总体严重血液学毒性风险增加无关。在紫杉烷类药物下，gBRCA1/2m 患者可能有更高的血液学毒性 G3-4 风险，需要进一步研究。
