American Association for Cancer Research
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Figure S1 from Breast Cancer Index Predicts Extended Endocrine Benefit to Individualize Selection of Patients with HR+ Early-stage Breast Cancer for 10 Years of Endocrine Therapy

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posted on 2023-03-31, 22:28 authored by Iris Noordhoek, Kai Treuner, Hein Putter, Yi Zhang, Jenna Wong, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Cornelis J.H. van de Velde, Catherine A. Schnabel, Gerrit-Jan Liefers

Forest plot and bar graph of predictive performance of BCI (H/I) in the Overall cohort (N=908) and the Primary AI subset (N=794).

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ARTICLE ABSTRACT

Individualized selection of patients with early-stage hormone receptor–positive (HR+) breast cancer for extended endocrine therapy (EET) is required to balance modest gains in outcome with toxicities of prolonged use. This study examined the Breast Cancer Index [BCI; HOXB13/IL17BR ratio (H/I)] as a predictive biomarker of EET benefit in patients from the Investigation on the Duration of Extended Adjuvant Letrozole trial. BCI was tested in primary tumor specimens from 908 patients randomized to receive 2.5 versus 5 years of extended letrozole. The primary endpoint was recurrence-free interval. Cox models and likelihood ratios tested the interaction between EET and BCI (H/I). BCI (H/I)-high significantly predicted benefit from extended letrozole in the overall cohort [HR 0.42; 95% confidence interval (CI), 0.21–0.84; P = 0.011] and any aromatase inhibitor subset [HR 0.34; 95% CI, 0.16–0.73; P = 0.004), whereas BCI (H/I)-low patients did not derive significant benefit (HR 0.95; 95% CI, 0.58–1.56; P = 0.84 and HR 0.90; 95% CI, 0.53–1.55; P = 0.71, respectively) treatment to biomarker interaction was significant (P = 0.045, P = 0.025, respectively). BCI identified approximately 50% of patients with clinically high-risk disease that did not benefit, and with clinically low-risk disease that derived significant benefit, from an additional 2.5 years of EET. BCI (H/I) predicted preferential benefit from 5 versus 2.5 years of EET and identified patients with improved outcomes from completing 10 years of adjuvant endocrine therapy. Findings expand the clinical utility of BCI (H/I) to a broader range of patients and beyond prognostic risk factors as a predictive endocrine response biomarker for early-stage HR+ breast cancer.

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