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

Clin Cancer Res. 2024 May 1;30(9):1984-1991. doi: 10.1158/1078-0432.CCR-23-1977.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Aromatase Inhibitors
  • Letrozole
  • Nitriles
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Triazoles