Breast Cancer Index and Prediction of Extended Aromatase Inhibitor Therapy Benefit in Hormone Receptor-Positive Breast Cancer from the NRG Oncology/NSABP B-42 Trial

Eleftherios P Mamounas; Hanna Bandos; Priya Rastogi; Yi Zhang; Kai Treuner; Peter C Lucas; Charles E Geyer Jr; Louis Fehrenbacher; Stephen K Chia; Adam M Brufsky; Janice M Walshe; Gamini S Soori; Shaker Dakhil; Soonmyung Paik; Sandra M Swain; Dennis C Sgroi; Catherine A Schnabel; Norman Wolmark

doi:10.1158/1078-0432.CCR-23-1977

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Breast Cancer Index and Prediction of Extended Aromatase Inhibitor Therapy Benefit in Hormone Receptor-Positive Breast Cancer from the NRG Oncology/NSABP B-42 Trial

Authors: Eleftherios P Mamounas ; Hanna Bandos ; Priya Rastogi ; Yi Zhang ; Kai Treuner ; Peter C Lucas ; Charles E Geyer Jr ; Louis Fehrenbacher ; Stephen K Chia ; Adam M Brufsky ; Janice M Walshe ; Gamini S Soori ; Shaker Dakhil ; Soonmyung Paik ; Sandra M Swain ; Dennis C Sgroi ; Catherine A Schnabel ; Norman Wolmark

Citation: CLINICAL CANCER RESEARCH, Vol.30(9) : 1984-1991, 2024-05

Journal Title: CLINICAL CANCER RESEARCH

ISSN: 1078-0432

Issue Date: 2024-05

MeSH: Adult ; Aged ; Aromatase Inhibitors* / therapeutic use ; Breast Neoplasms* / drug therapy ; Breast Neoplasms* / metabolism ; Breast Neoplasms* / pathology ; Female ; Humans ; Letrozole* / administration & dosage ; Letrozole* / therapeutic use ; Middle Aged ; Nitriles / therapeutic use ; Prognosis ; Receptors, Estrogen* / metabolism ; Receptors, Progesterone / metabolism ; Treatment Outcome ; Triazoles / administration & dosage ; Triazoles / therapeutic use

Abstract: Purpose: BCI (H/I) has been shown to predict extended endocrine therapy (EET) benefit. We examined BCI (H/I) for EET benefit prediction in NSABP B-42, which evaluated extended letrozole therapy (ELT) in patients with hormone receptor-positive breast cancer after 5 years of ET.

Experimental design: A stratified Cox model was used to analyze RFI as the primary endpoint, with DR, BCFI, and DFS as secondary endpoints. Because of a nonproportional effect of ELT on DR, time-dependent analyses were performed.

Results: The translational cohort included 2,178 patients (45% BCI (H/I)-High, 55% BCI (H/I)-Low). ELT showed an absolute 10-year RFI benefit of 1.6% (P = 0.10), resulting in an underpowered primary analysis (50% power). ELT benefit and BCI (H/I) did not show a significant interaction for RFI (BCI (H/I)-Low: 10 years absolute benefit 1.1% [HR, 0.70; 95% confidence interval (CI), 0.43-1.12; P = 0.13]; BCI (H/I)-High: 2.4% [HR, 0.83; 95% CI, 0.55-1.26; P = 0.38]; Pinteraction = 0.56). Time-dependent DR analysis showed that after 4 years, BCI (H/I)-High patients had significant ELT benefit (HR = 0.29; 95% CI, 0.12-0.69; P < 0.01), whereas BCI (H/I)-Low patients were less likely to benefit (HR, 0.68; 95% CI, 0.33-1.39; P = 0.29; Pinteraction = 0.14). Prediction of ELT benefit by BCI (H/I) was more apparent in the HER2- subset after 4 years (ELT-by-BCI (H/I) Pinteraction = 0.04).

Conclusions: BCI (H/I)-High versus BCI (H/I)-Low did not show a statistically significant difference in ELT benefit for the primary endpoint (RFI). However, in time-dependent DR analysis, BCI (H/I)-High patients experienced statistically significant benefit from ELT after 4 years, whereas (H/I)-Low patients did not. Because BCI (H/I) has been validated as a predictive marker of EET benefit in other trials, additional follow-up may enable further characterization of BCI's predictive ability.