Division of Cancer Medicine, Peter MacCallum Cancer Centre, Australia.
J Clin Oncol. 2013 Sep 1;31(25):3091-9. doi: 10.1200/JCO.2012.47.8313. Epub 2013 Aug 5.
To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers.
Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up.
Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 BRCA2 mutation carriers with 100 CBCs over 4,392 person-years of prospective follow-up. HRs did not differ by estrogen receptor status of the first BC (missing for 56% of cases).
This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.
确定乳腺癌（BC）辅助他莫昔芬治疗是否与 BRCA1 和/或 BRCA2 突变携带者的对侧乳腺癌（CBC）风险降低相关。
对国际 BRCA1、BRCA2 携带者队列研究、凯思琳·坎宁安基金会乳腺癌家族研究联盟和乳腺癌家族登记处的汇总观察队列数据进行分析，这些数据在入组时和随访时通过自我报告收集。合格的女性是自 1970 年以来被诊断为单侧 BC 的 BRCA1 和 BRCA2 突变携带者，并且在首次 BC 之前没有任何其他侵袭性癌症或他莫昔芬使用。使用 Cox 回归估计与他莫昔芬使用相关的 CBC 的风险比（HR），调整了年份和诊断时的年龄、国家以及双侧卵巢切除术，并在对侧乳房切除术、死亡或失访时进行了 censoring。
在 1583 名 BRCA1 和 881 名 BRCA2 突变携带者中，分别有 383 名（24%）和 454 名（52%）在首次 BC 诊断后接受了他莫昔芬治疗。在 20104 人年的观察期间，共发生了 520 例 CBC。调整后的 HR 估计值分别为 0.38（95%CI，0.27 至 0.55）和 0.33（95%CI，0.22 至 0.50），分别为 BRCA1 和 BRCA2 突变携带者。在左截断入组队列后，根据 657 名 BRCA1 和 426 名 BRCA2 突变携带者的前瞻性随访，在 4392 人年中发生了 100 例 CBC，调整后的 HR 估计值分别为 0.58（95%CI，0.29 至 1.13）和 0.48（95%CI，0.22 至 1.05）。HR 与首次 BC 的雌激素受体状态无关（56%的病例缺失）。
本研究提供了证据，表明他莫昔芬的使用与 BRCA1 和 BRCA2 突变携带者的 CBC 风险降低相关。对这些队列的进一步随访将为未来的前瞻性分析提供更大的统计效力。
