Breast Cancer Index is a predictive biomarker of treatment benefit and outcome from extended tamoxifen therapy: final analysis of the Trans-aTTom study

John M S Bartlett, Dennis C Sgroi, Kai Treuner, Yi Zhang, Tammy Piper, Ranelle C Salunga, Ikhlaaq Ahmed, Lucy Doos, Sarah Thornber, Karen J Taylor, Elena F Brachtel, Sarah J Pirrie, Catherine A Schnabel, Daniel Rea

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: The Breast Cancer Index (BCI) HOXB13/IL17BR (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor-positive (HR+) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)'s predictive performance.

EXPERIMENTAL DESIGN: BCI results were available for 2,445 aTTom trial patients. The primary endpoint of recurrence-free interval (RFI) and secondary endpoints of disease-free interval (DFI) and disease-free survival (DFS) were examined using Cox proportional hazards regression and log-rank test.

RESULTS: Final analysis of the overall study population (N = 2,445) did not show a significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% confidence interval (CI), 0.69-1.16; P = 0.401]. Both the overall study population and N0 group were underpowered due to the low event rate in the N0 group. In a pre-planned analysis of the N+ subset (N = 789), BCI (H/I)-High patients derived significant benefit from extended tamoxifen (9.7% absolute benefit: HR, 0.33; 95% CI, 0.14-0.75; P = 0.016), whereas BCI (H/I)-Low patients did not (-1.2% absolute benefit; HR, 1.11; 95% CI, 0.76-1.64; P = 0.581). A significant treatment-to-biomarker interaction was demonstrated on the basis of RFI, DFI, and DFS (P = 0.037, 0.040, and 0.025, respectively). BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen in the N+/HER2- subgroup (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15-0.81; P = 0.047). A three-way interaction evaluating BCI (H/I), treatment, and HER2 status was not statistically significant (P = 0.849).

CONCLUSIONS: Novel findings demonstrate that BCI (H/I) significantly predicts benefit from extended tamoxifen in HR+ N+ patients with HER2- disease. Moreover, BCI (H/I) demonstrates significant treatment to biomarker interaction across survival outcomes.

Original languageEnglish
Pages (from-to)1871-1880
Number of pages10
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Volume28
Issue number9
Early online date10 Feb 2022
DOIs
Publication statusPublished - 2 May 2022

Bibliographical note

©2022 The Authors; Published by the American Association for Cancer Research.

Keywords

  • Antineoplastic Agents, Hormonal/therapeutic use
  • Biomarkers
  • Breast Neoplasms/diagnosis
  • Chemotherapy, Adjuvant/methods
  • Disease-Free Survival
  • Female
  • Humans
  • Neoplasm Recurrence, Local/drug therapy
  • Prognosis
  • Tamoxifen/therapeutic use
  • Treatment Outcome

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