辅助卵巢功能抑制（OFS）联合口服内分泌治疗可改善绝经前激素受体阳性（HR）乳腺癌患者的预后，但会增加不良反应。目前缺乏用于选择最有可能从基于 OFS 的治疗中受益的患者的基因组生物标志物。旨在评估乳腺癌指数 (BCI) 对患有 HR 乳腺癌的绝经前女性的 OFS 益处的预测和预后表现。这项前瞻性回顾性转化研究使用来自卵巢功能抑制试验（SOFT）的女性患者的所有可用肿瘤组织样本。这些个体被随机分配接受 5 年的单独他莫昔芬辅助治疗、他莫昔芬加 OFS 或依西美坦加 OFS 治疗。 BCI 测试是在不了解临床数据和结果的情况下进行的。先验假设是 BCI HOXB13/IL17BR 比值 (BCI[H/I]) 高的肿瘤将从 OFS 中获益更多，而高 BCI 预示着该人群的预后较差。设置跨越国际多个中心。参与者包括患有 HR 早期乳腺癌的绝经前女性患者，其标本来自国际乳腺癌研究组肿瘤存储库，可供提取 RNA。数据收集时间为2003年12月至2021年4月，分析时间为2022年5月至2022年10月。主要终点是用于预测分析的无乳腺癌间隔（BCFI）和用于预后分析的远处无复发间隔（DRFI）。肿瘤SOFT 意向治疗人群中的 3047 名女性患者中有 1718 名可以获得标本。 1687 名患者 (98.2%) 的样本能够产生足够的 RNA 用于 BCI 测试，这代表了母试验人群。中位随访时间 (IQR) 为 12 (10.5-13.4) 年，512 名患者 (30.3%) 年龄小于 40 岁。 972 名患者 (57.6%) 的肿瘤 BCI(H/I) 低，715 名患者 (42.4%) 的肿瘤 BCI(H/I) 高。肿瘤分类为 BCI(H/I)-低的患者，依西美坦加 OFS 的 12 年 BCFI 绝对获益为 11.6%（风险比 [HR]，0.48 [95% CI，0.33-0.71]），绝对获益相对于单用他莫昔芬，他莫昔芬加 OFS 的获益为 7.3%（HR，0.69 [95% CI，0.48-0.97]）。相比之下，BCI(H/I) 高肿瘤患者并未从依西美坦加 OFS 中获益（绝对获益，-0.4%；HR，1.03 [95% CI，0.70-1.53​​]；交互作用 P = .006）或他莫昔芬联合 OFS（绝对获益，-1.2%；HR，1.05 [95% CI，0.72-1.54]；交互作用 P = .11）与单用他莫昔芬相比。 BCI 连续指数在 DRFI 的 N0 亚组中具有显着的预后意义（n = 1110；P = .004），BCI 低风险、中风险和高风险的 12 年 DRFI 分别为 95.9%、90.8% 和 86.3%在这项针对 SOFT 入组患者的前瞻性回顾性转化研究中，BCI 被证实对患有 HR 乳腺癌的绝经前妇女具有预后作用。对于 BCI(H/I) 低的肿瘤患者而言，含 OFS 的辅助内分泌治疗的益处大于 BCI(H/I) 高的肿瘤患者。 BCI（H/I）低状态可能会识别出可能从这种更强化的内分泌治疗中受益的绝经前患者。

Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.This prospective-retrospective translational study used all available tumor tissue samples from female patients from the Suppression of Ovarian Function Trial (SOFT). These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. BCI testing was performed blinded to clinical data and outcome. The a priori hypothesis was that BCI HOXB13/IL17BR ratio (BCI[H/I])-high tumors would benefit more from OFS and high BCI portended poorer prognosis in this population. Settings spanned multiple centers internationally. Participants included premenopausal female patients with HR+ early breast cancer with specimens in the International Breast Cancer Study Group tumor repository available for RNA extraction. Data were collected from December 2003 to April 2021 and were analyzed from May 2022 to October 2022.Primary end points were breast cancer-free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses.Tumor specimens were available for 1718 of the 3047 female patients in the SOFT intention-to-treat population. The 1687 patients (98.2%) who had specimens that yielded sufficient RNA for BCI testing represented the parent trial population. The median (IQR) follow-up time was 12 (10.5-13.4) years, and 512 patients (30.3%) were younger than 40 years. Tumors were BCI(H/I)-low for 972 patients (57.6%) and BCI(H/I)-high for 715 patients (42.4%). Patients with tumors classified as BCI(H/I)-low exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48 [95% CI, 0.33-0.71]) and an absolute benefit of 7.3% from tamoxifen plus OFS (HR, 0.69 [95% CI, 0.48-0.97]) relative to tamoxifen alone. In contrast, patients with BCI(H/I)-high tumors did not benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03 [95% CI, 0.70-1.53]; P for interaction = .006) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05 [95% CI, 0.72-1.54]; P for interaction = .11) compared with tamoxifen alone. BCI continuous index was significantly prognostic in the N0 subgroup for DRFI (n = 1110; P = .004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk N0 cancers, respectively.In this prospective-retrospective translational study of patients enrolled in SOFT, BCI was confirmed as prognostic in premenopausal women with HR+ breast cancer. The benefit from OFS-containing adjuvant endocrine therapy was greater for patients with BCI(H/I)-low tumors than BCI(H/I)-high tumors. BCI(H/I)-low status may identify premenopausal patients who are likely to benefit from this more intensive endocrine therapy.