{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:58:12Z","timestamp":1793404692913,"version":"4.5.0"},"reference-count":22,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n The Breast Cancer Index (BCI) previously identified premenopausal patients with tumors in which the ratio of expression of\n HOXB13<\/jats:italic>\n relative to\n IL17BR<\/jats:italic>\n (hereafter, BCI [H\/I]\u2013low tumors) as likely to derive greatest benefit from ovarian function suppression (OFS)\u2013containing adjuvant therapy in the Suppression of Ovarian Function Trial (SOFT) trial.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To assess BCI as a predictive biomarker of benefit from exemestane plus OFS vs tamoxifen plus OFS and to validate BCI as a prognostic biomarker for premenopausal patients.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This prognostic study used a prospective-retrospective translational design within the Tamoxifen and Exemestane (TEXT) and SOFT trials (enrolled November 2003 to April 2011). Blinded BCI testing in all available tumor samples was completed in March 2024. Premenopausal women with hormone receptor\u2013positive breast cancer randomized to tamoxifen plus OFS or exemestane plus OFS who had BCI assessed were included. Analysis occurred from March to August 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n 5 years of adjuvant tamoxifen plus OFS or exemestane plus OFS.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcomes were breast cancer-free interval (BCFI) for predictive analyses and distant recurrence-free interval (DRFI) for prognostic analyses after a median follow-up of 13 years in the TEXT cohort. Secondary objectives examined the predictive performance of BCI (H\/I) in the combined TEXT and SOFT cohort overall and in prespecified clinical subgroups.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 1782 patients in the TEXT study, 1034 (58.0%) had BCI (H\/I)\u2013low tumors; 915 (51.3%) of patients had N0 disease and 1077 (60.4%) were younger than 45 years. Patients with BCI (H\/I)\u2013low tumors had a 6.6% absolute benefit in 12-year BCFI (HR, 0.61; 95% CI, 0.44-0.85) for exemestane plus OFS vs tamoxifen plus OFS, while those with BCI (H\/I)\u2013high tumors had a 6.3% absolute benefit (HR, 0.78; 95% CI, 0.57-1.07;\n P<\/jats:italic>\n for interaction\u2009=\u2009.29). Results were consistent in the combined TEXT plus SOFT cohort (2896 patients) and adjusting for clinicopathological variables. Clinical subgroup analyses consistently showed benefit of exemestane plus OFS vs tamoxifen plus OFS for BCI (H\/I)\u2013low tumors, and more variable relative treatment effects among BCI (H\/I)\u2013high tumors, including by age. Post hoc exploratory time-varying estimates suggested the treatment\u2009\u00d7\u2009BCI associations may differ in years 0 to 5 vs greater than 5 years. BCI and BCI N+ as continuous indices were prognostic for distant recurrence in N0 (HR, 1.27; 95% CI, 1.11-1.44;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) and N1 (HR, 1.58; 95% CI, 1.21-2.05;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) cancers. The 12-year DRFI was 96.3%, 90.3%, and 84.9% for BCI low-, intermediate-, and high-risk N0 cancers, respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this study of premenopausal women with hormone receptor\u2013positive breast cancer, BCI (H\/I) status did not clearly predict greater benefit of adjuvant exemestane plus OFS vs tamoxifen plus OFS for women with BCI (H\/I)\u2013low tumors than for those with BCI (H\/I)\u2013high tumors; BCI continuous indices were reconfirmed as prognostic for premenopausal women. These findings support prior results of SOFT, which compared tamoxifen-alone vs OFS with either exemestane or tamoxifen, indicating premenopausal patients with BCI (H\/I)\u2013low tumors may benefit from more intensive endocrine therapy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.40931","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T16:00:44Z","timestamp":1762185644000},"page":"e2540931","source":"Crossref","is-referenced-by-count":4,"title":["Assessment of Adjuvant Endocrine Therapy With Ovarian Function Suppression by Breast Cancer Index"],"prefix":"10.1001","volume":"8","author":[{"given":"Ruth M.","family":"O\u2019Regan","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Rochester, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Ren","sequence":"additional","affiliation":[{"name":"IBCSG Statistical Center, Division of Biostatistics, 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