患有早期激素受体阳性乳腺癌的绝经前妇女的乳腺癌指数。

IF 28.4 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Ruth M O'Regan, Yi Zhang, Gini F Fleming, Prudence A Francis, Roswitha Kammler, Giuseppe Viale, Patrizia Dell'Orto, Istvan Lang, Meritxell Bellet, Herve R Bonnefoi, Carlo Tondini, Federica Villa, Antonio Bernardo, Eva M Ciruelos, Patrick Neven, Per Karlsson, Bettina Müller, Wolfram Jochum, Khalil Zaman, Silvana Martino, Charles E Geyer, Katarzyna J Jerzak, Nancy E Davidson, Robert E Coleman, James N Ingle, Marion T van Mackelenbergh, Sherene Loi, Marco Colleoni, Catherine A Schnabel, Kai Treuner, Meredith M Regan
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引用次数: 0

摘要

重要性:口服内分泌治疗辅助卵巢功能抑制(OFS)可改善激素受体阳性(HR+)乳腺癌绝经前患者的预后,但会增加不良反应。目前还缺乏一种基因组生物标志物来选择最有可能从基于OFS的治疗中获益的患者:目的:评估乳腺癌指数(BCI)对HR+乳腺癌绝经前女性OFS获益的预测性和预后性:这项前瞻性-回顾性转化研究使用了来自卵巢功能抑制试验(SOFT)女性患者的所有可用肿瘤组织样本。这些患者被随机分配接受为期5年的单独他莫昔芬辅助治疗、他莫昔芬加OFS治疗或依西美坦加OFS治疗。BCI测试在临床数据和结果盲法下进行。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BCI高的肿瘤预示着预后较差。研究地点横跨国际多个中心。研究对象包括HR+早期乳腺癌绝经前女性患者,这些患者的标本在国际乳腺癌研究组肿瘤库中可用于提取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:主要终点是预测分析中的无乳腺癌间隔期(BCFI)和预后分析中的无远处复发间隔期(DRFI):在SOFT意向治疗人群的3047名女性患者中,有1718名患者获得了肿瘤标本。1687名患者(98.2%)的标本可提供足够的RNA用于BCI检测,这些患者代表了母试验人群。中位(IQR)随访时间为12(10.5-13.4)年,512名患者(30.3%)的年龄小于40岁。972名患者(57.6%)的肿瘤为BCI(H/I)-低,715名患者(42.4%)的肿瘤为BCI(H/I)-高。与单用他莫昔芬相比,BCI(H/I)-低的肿瘤患者在依西美坦加用OFS的12年中,BCFI的绝对获益率为11.6%(危险比[HR],0.48 [95% CI,0.33-0.71]),他莫昔芬加用OFS的绝对获益率为7.3%(HR,0.69 [95% CI,0.48-0.97])。相反,与单用他莫昔芬相比,BCI(H/I)高的肿瘤患者从依西美坦加用OFS(绝对获益为-0.4%;HR,1.03 [95% CI,0.70-1.53];交互作用P = .006)或他莫昔芬加用OFS(绝对获益为-1.2%;HR,1.05 [95% CI,0.72-1.54];交互作用P = .11)中均未获益。在N0亚组中,BCI连续指数对DRFI(n = 1110;P = .004)有明显的预后作用,BCI低危、中危和高危N0癌症的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+乳腺癌的绝经前女性具有预后作用。BCI(H/I)-低肿瘤患者从含OFS的辅助内分泌治疗中获益大于BCI(H/I)-高肿瘤患者。BCI(H/I)-低状态可识别出可能从这种更密集的内分泌治疗中获益的绝经前患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor-Positive Breast Cancer.

Importance: 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.

Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.

Design, setting, and participants: 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.

Main outcomes and measures: Primary end points were breast cancer-free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses.

Results: 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.

Conclusions and relevance: 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.

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来源期刊
Jama Oncology
Jama Oncology Medicine-Oncology
CiteScore
37.50
自引率
1.80%
发文量
423
期刊介绍: At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science. Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers. We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.
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