Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
INSERM, U900, Paris, France.
J Natl Cancer Inst. 2023 Nov 8;115(11):1318-1328. doi: 10.1093/jnci/djad116.
Radiation-induced secondary breast cancer (BC) may be a concern after radiation therapy (RT) for primary breast cancer (PBC), especially in young patients with germline (g)BRCA-associated BC who already have high contralateral BC (CBC) risk and potentially increased genetic susceptibility to radiation. We sought to investigate whether adjuvant RT for PBC increases the risk of CBC in patients with gBRCA1/2-associated BC.
The gBRCA1/2 pathogenic variant carriers diagnosed with PBC were selected from the prospective International BRCA1/2 Carrier Cohort Study. We used multivariable Cox proportional hazards models to investigate the association between RT (yes vs no) and CBC risk. We further stratified for BRCA status and age at PBC diagnosis (<40 and >40 years). Statistical significance tests were 2-sided.
Of 3602 eligible patients, 2297 (64%) received adjuvant RT. Median follow-up was 9.6 years. The RT group had more patients with stage III PBC than the non-RT group (15% vs 3%, P < .001), received chemotherapy more often (81% vs 70%, P < .001), and received endocrine therapy more often (50% vs 35%, P < .001). The RT group had an increased CBC risk compared with the non-RT group (adjusted hazard ratio [HR] = 1.44; 95% confidence interval [CI] = 1.12 to 1.86). Statistical significance was observed in gBRCA2 (HR = 1.77; 95% CI = 1.13 to 2.77) but not in gBRCA1 pathogenic variant carriers (HR = 1.29; 95% CI = 0.93 to 1.77; P = .39 for interaction). In the combined gBRCA1/2 group, patients irradiated when they were younger than or older than 40 years of age at PBC diagnosis showed similar risks (HR = 1.38; 95% CI = 0.93 to 2.04 and HR = 1.56; 95% CI = 1.11 to 2.19, respectively).
RT regimens minimizing contralateral breast dose should be considered in gBRCA1/2 pathogenic variant carriers.
原发性乳腺癌（PBC）放射治疗（RT）后可能会引发继发性乳腺癌（BC），尤其是携带种系（g）BRCA 相关 BC 的年轻患者，她们已经具有较高的对侧乳腺癌（CBC）风险，并且可能对辐射具有更高的遗传易感性。我们旨在研究 PBC 的辅助 RT 是否会增加携带 gBRCA1/2 相关 BC 的患者的 CBC 风险。
从前瞻性国际 BRCA1/2 携带者队列研究中选择 gBRCA1/2 致病性变异携带者诊断为 PBC 的患者。我们使用多变量 Cox 比例风险模型来研究 RT（是与否）与 CBC 风险之间的关联。我们进一步对 BRCA 状态和 PBC 诊断时的年龄（<40 岁和>40 岁）进行分层。统计显著性检验为双侧。
在 3602 名合格患者中，有 2297 名（64%）接受了辅助 RT。中位随访时间为 9.6 年。RT 组的 III 期 PBC 患者多于非 RT 组（15% vs 3%，P<0.001），更常接受化疗（81% vs 70%，P<0.001），并且更常接受内分泌治疗（50% vs 35%，P<0.001）。与非 RT 组相比，RT 组的 CBC 风险增加（调整后的危险比 [HR] = 1.44；95%置信区间 [CI] = 1.12 至 1.86）。在 gBRCA2 中观察到统计学意义（HR = 1.77；95%CI = 1.13 至 2.77），但在 gBRCA1 致病性变异携带者中未观察到统计学意义（HR = 1.29；95%CI = 0.93 至 1.77；P = 0.39 用于交互作用）。在 gBRCA1/2 联合组中，在 PBC 诊断时年龄小于或大于 40 岁时接受放疗的患者具有相似的风险（HR = 1.38；95%CI = 0.93 至 2.04 和 HR = 1.56；95%CI = 1.11 至 2.19）。
应考虑在 gBRCA1/2 致病性变异携带者中使用最小化对侧乳房剂量的 RT 方案。
