Breast cancer index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—to offer more? (aTTom) trial

Research output: Contribution to journalArticlepeer-review


  • J M S Bartlett
  • D C Sgroi
  • K Treuner
  • Y Zhang
  • T Piper
  • R Salunga
  • E F Brachtel
  • C A Schnabel

Colleges, School and Institutes

External organisations

  • Edinburgh Cancer Research Centre, University of Edinburgh
  • Ontario Institute for Cancer Research
  • Massachusetts General Hospital
  • Biotheranostics Inc


Background: Extending the duration of adjuvant endocrine therapy reduces the risk of recurrence in a subset of women with early-stage hormone receptor-positive (HR+) breast cancer. Validated predictive biomarkers of endocrine response could significantly improve patient selection for extended therapy. Breast cancer index (BCI) [HOXB13/IL17BR ratio (H/I)] was evaluated for its ability to predict benefit from extended endocrine therapy in patients previously randomized in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial.

Patients and methods: Trans-aTTom is a multi-institutional, prospective–retrospective study in patients with available formalin-fixed paraffin-embedded primary tumor blocks. BCI testing and central determination of estrogen receptor (ER) and progesterone receptor (PR) status by immunohistochemistry were carried out blinded to clinical outcome. Survival endpoints were evaluated using Kaplan–Meier analysis and Cox regression with recurrence-free interval (RFI) as the primary endpoint. Interaction between extended endocrine therapy and BCI (H/I) was assessed using the likelihood ratio test.

Results: Of 583 HR+, N+ patients analyzed, 49% classified as BCI (H/I)-High derived a significant benefit from 10 versus 5 years of tamoxifen treatment [hazard ratio (HR): 0.35; 95% confidence interval (CI) 0.15–0.86; 10.2% absolute risk reduction based on RFI, P = 0.027]. BCI (H/I)-low patients showed no significant benefit from extended endocrine therapy (HR: 1.07; 95% CI 0.69–1.65; −0.2% absolute risk reduction; P = 0.768). Continuous BCI (H/I) levels predicted the magnitude of benefit from extended tamoxifen, whereas centralized ER and PR did not. Interaction between extended tamoxifen treatment and BCI (H/I) was statistically significant (P = 0.012), adjusting for clinicopathological factors.

Conclusion: BCI by high H/I expression was predictive of endocrine response and identified a subset of HR+, N+ patients with significant benefit from 10 versus 5 years of tamoxifen therapy. These data provide further validation, consistent with previous MA.17 data, establishing level 1B evidence for BCI as a predictive biomarker of benefit from extended endocrine therapy.

Trial registration: ISRCTN17222211; NCT00003678.


Original languageEnglish
Pages (from-to)1776-1783
Number of pages8
JournalAnnals of Oncology
Issue number11
Early online date28 Aug 2019
Publication statusPublished - Nov 2019


  • BCI, early-stage breast cancer, endocrine benefit, molecular signature, predictive biomarker

ASJC Scopus subject areas