Terra Lara, Boekel Naomi B, Hooning Maartje H, Collee Margriet, Schmidt Marjanka K, Adank Muriel A, Kok Marleen, Aleman Berthe M P, Jager Agnes, Sattler Margriet G A, Maas Angela H E M, Schaapveld Michael, van Leeuwen Flora E
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066, Amsterdam, CX, The Netherlands.
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Breast Cancer Res Treat. 2025 Feb;209(3):573-583. doi: 10.1007/s10549-024-07516-2. Epub 2024 Oct 31.
Breast cancer (BC) treatment can induce adverse events, such as cardiovascular disease (CVD). Defective DNA repair, as in carriers of BRCA1/2 pathogenic variants (BRCA1/2pv), may contribute to CVD risk. We aimed to study if female BRCA1/2pv carriers are more sensitive to develop CVD after BC treatment than BC patients without a known BRCA1/2pv.
In a hospital-based cohort of 17,300 female BC patients, we identified 509 BRCA1/2pv carriers. Cardiovascular morbidity and mortality were assessed through hospital charts and general practitioner questionnaires. We performed Cox regression analyses comparing BRCA1/2pv carriers with all other BC patients, adjusting for age, radiotherapy regimen, chemotherapy regimen, and smoking status.
Median follow-up time since BC treatment was 14 years. In total, 1108 women experienced ischemic heart disease (IHD), of whom 20 (1.8%) were BRCA1/2pv carriers. Heart failure (HF) was diagnosed in 638 women, of whom 10 (1.6%) were BRCA1/2pv carriers. BRCA1/2pv carriership was associated with a slight not statistically significant increase of IHD (adjHR 1.51, 95%CI 0.93; 2.42), but not with risk of HF (adjHR 0.86, 95%CI 0.44; 1.69). The association between radiotherapy and IHD risk was not significantly different between BRCA1/2pv carriers [HR 2.30 (95%CI 0.79; 6.66)] and other BC patients (HR 1.50, 95%CI 1.30; 1.73). Associations between anthracycline-based chemotherapy and HF risk also did not differ between carriers and other BC patients (HRs of 4.02 (95%CI 1.02; 15.77) and 2.31 (95%CI 1.77; 3.01), respectively).
In BRCA1/2pv BC patients, we found no evidence for a higher risk of BC treatment-related CVD than in other BC patients.
乳腺癌(BC)治疗可引发不良事件,如心血管疾病(CVD)。DNA修复缺陷,如携带BRCA1/2致病变异(BRCA1/2pv)的患者,可能会增加患CVD的风险。我们旨在研究携带BRCA1/2pv的女性乳腺癌患者在接受BC治疗后是否比无已知BRCA1/2pv的BC患者更易发生CVD。
在一个基于医院的包含17300名女性BC患者的队列中,我们识别出509名BRCA1/2pv携带者。通过医院病历和全科医生调查问卷评估心血管疾病的发病率和死亡率。我们进行了Cox回归分析,将BRCA1/2pv携带者与所有其他BC患者进行比较,并对年龄、放疗方案、化疗方案和吸烟状况进行了调整。
自BC治疗后的中位随访时间为14年。共有1108名女性发生缺血性心脏病(IHD),其中20名(1.8%)为BRCA1/2pv携带者。638名女性被诊断为心力衰竭(HF),其中10名(1.6%)为BRCA1/2pv携带者。携带BRCA1/2pv与IHD的轻微增加相关,但无统计学意义(调整后风险比[adjHR]为1.51,95%置信区间[CI]为0.93;2.42),但与HF风险无关(adjHR为0.86,95%CI为0.44;1.69)。BRCA1/2pv携带者[风险比(HR)为2.30(95%CI为0.79;6.66)]与其他BC患者(HR为1.50,95%CI为1.30;1.73)相比,放疗与IHD风险之间的关联无显著差异。基于蒽环类化疗与HF风险之间的关联在携带者和其他BC患者之间也无差异(HR分别为4.02(95%CI为1.02;15.77)和2.31(95%CI为1.77;3.01))。
在携带BRCA1/2pv的BC患者中,我们没有发现证据表明其发生与BC治疗相关的CVD的风险高于其他BC患者。