Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Mathematics and Statistics, University of Vermont, Burlington, Vermont.
Cancer. 2021 Mar 1;127(5):700-708. doi: 10.1002/cncr.33318. Epub 2020 Dec 8.
Endocrine therapy resistance is a major cause of distant recurrence (DR) in hormone receptor-positive breast cancer. This study evaluated differences in survival after DR in patients treated with different adjuvant endocrine therapy regimens in the Breast International Group (BIG) 1-98 trial.
BIG 1-98 compared 5 years of adjuvant treatment among 4 arms: tamoxifen (T), letrozole (L), tamoxifen followed by letrozole (TL), and letrozole followed by tamoxifen (LT). After a median follow-up of 8.1 years, 911 of 8010 patients (T, 302; L, 285; TL, 170; and LT, 154) had DR as the site of first recurrence. Univariate and multivariate Cox analyses were performed to determine features associated with post-DR survival.
The median follow-up time after DR was 59 months (interquartile range, 29-88 months). Among all patients with DR, 38.1% were 65 years old or older at enrollment, 61.9% had tumors larger than 2 cm, and 69.7% were node positive. Neoadjuvant or adjuvant chemotherapy was administered to 35.6% of the patients. There was no difference in post-DR survival by treatment arm (median survival, 20.8 months for T, 17.9 months for L, 17.3 months for TL, and 20.8 months for LT; P = .21). In multivariate analysis, older patients (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.15-1.59) and patients with tumors larger than 2 cm (HR, 1.19; 95% CI, 1.00-1.41), 4 or more positive nodes (HR, 1.31; 95% CI, 1.05-1.64), progesterone receptor (PR)-negative tumors (HR, 1.25; 95% CI, 1.02-1.52), or shorter disease-free survival (DFS) had significantly worse post-DR survival.
Treatment with adjuvant T, L, or their sequences was not associated with differences in survival after DR. Significant differences in survival were observed by age, primary tumor size, nodal and PR status, and DFS, and this suggests that traditional baseline high-risk features remain prognostic in the metastatic setting.
内分泌治疗耐药是激素受体阳性乳腺癌远处复发（DR）的主要原因。本研究评估了乳腺国际集团（BIG）1-98 试验中不同辅助内分泌治疗方案治疗患者 DR 后的生存差异。
BIG 1-98 比较了 4 个治疗组 5 年的辅助治疗：他莫昔芬（T）、来曲唑（L）、他莫昔芬序贯来曲唑（TL）和来曲唑序贯他莫昔芬（LT）。中位随访 8.1 年后，8010 例患者中有 911 例（T 组 302 例，L 组 285 例，TL 组 170 例，LT 组 154 例）发生了 DR 作为首次复发的部位。进行单变量和多变量 Cox 分析以确定与 DR 后生存相关的特征。
DR 后中位随访时间为 59 个月（四分位距，29-88 个月）。所有 DR 患者中，38.1%在入组时年龄为 65 岁或以上，61.9%肿瘤大于 2cm，69.7%有淋巴结转移。35.6%的患者接受了新辅助或辅助化疗。治疗组之间 DR 后生存无差异（中位生存时间：T 组 20.8 个月，L 组 17.9 个月，TL 组 17.3 个月，LT 组 20.8 个月；P=.21）。多变量分析显示，年龄较大的患者（风险比[HR]，1.35；95%置信区间[CI]，1.15-1.59）和肿瘤大于 2cm（HR，1.19；95%CI，1.00-1.41）、4 个或更多阳性淋巴结（HR，1.31；95%CI，1.05-1.64）、孕激素受体（PR）阴性肿瘤（HR，1.25；95%CI，1.02-1.52）或无病生存期（DFS）较短的患者 DR 后生存明显较差。
辅助 T、L 或其序贯治疗与 DR 后生存无差异。年龄、原发肿瘤大小、淋巴结和 PR 状态以及 DFS 的生存差异显著，这表明传统的基线高危特征在转移环境中仍然具有预后意义。
