1. Breast Cancer Index Predicts Extended Endocrine Benefit to Individualize Selection of Patients with HR + Early-stage Breast Cancer for 10 Years of Endocrine Therapy.
- Author
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Noordhoek I, Treuner K, Putter H, Zhang Y, Wong J, Meershoek-Klein Kranenbarg E, Duijm-de Carpentier M, van de Velde CJH, Schnabel CA, and Liefers GJ
- Subjects
- Antineoplastic Agents, Hormonal pharmacology, Aromatase Inhibitors pharmacology, Breast Neoplasms diagnosis, Breast Neoplasms mortality, Breast Neoplasms pathology, Chemotherapy, Adjuvant methods, Chemotherapy, Adjuvant statistics & numerical data, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Homeodomain Proteins analysis, Humans, Letrozole pharmacology, Letrozole therapeutic use, Middle Aged, Neoplasm Recurrence, Local prevention & control, Neoplasm Staging, Patient Selection, Prognosis, Prospective Studies, Receptors, Estrogen analysis, Receptors, Estrogen metabolism, Receptors, Interleukin-17 analysis, Receptors, Progesterone analysis, Receptors, Progesterone metabolism, Retrospective Studies, Time Factors, Antineoplastic Agents, Hormonal therapeutic use, Aromatase Inhibitors therapeutic use, Biomarkers, Tumor analysis, Breast Neoplasms therapy, Neoplasm Recurrence, Local epidemiology
- Abstract
Purpose: 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., Experimental Design: 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)., Results: 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., Conclusions: 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., (©2020 American Association for Cancer Research.)- Published
- 2021
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