Trans-aTTom: Breast Cancer Index for prediction of endocrine benefit and late distant recurrence (DR) in patients with HR+ breast cancer treated in the adjuvant tamoxifen—To offer more? (aTTom) trial.

Research output: Contribution to journalAbstractpeer-review

Authors

  • John Bartlett
  • Dennis Sgroi
  • Kai Treuner
  • Yi Zhang
  • Tammy Piper
  • Ranelle C. Salunga
  • Kristen M Basnet
  • Elena Brachtel
  • Catherine A. Schnabel

Colleges, School and Institutes

Abstract

Background: The aTTom study is a prospective phase III trial that randomized 6953 HR+ women to stop or continue tamoxifen (TAM) for 5 more years after completing at least 4 years of prior TAM. Results at 9 years of median follow-up demonstrated fewer breast cancer recurrences (21% vs 25%; RR= 0.86 [95% CI 0.77-0.96]; P = 0.006) and reduced breast cancer mortality (13% vs 15%; HR= 0.91 [95% CI 0.80-1.04]; P = 0.18) but increased incidence of endometrial cancer with longer TAM use (P <0.0001). The Breast Cancer Index (BCI) is a gene expression based signature that stratifies patients based on the risk of overall (0-10y) and late (post-5y) DR and predicted the likelihood of benefit from extended endocrine therapy in MA.17. This Translational aTTom (Trans-aTTom) study is a large-scale validation of the predictive ability of BCI for extended endocrine therapy (EET) benefit. 
Methods: Patients treated in the aTTom trial with available primary tumor tissue were eligible for this multi-institutional prospective-retrospective study. Primary and secondary endpoints were recurrence-free interval (RFI) and disease-free interval (DFI), respectively. Statistical significance level for RFI was set at 0.0336 as per statistical plan. Kaplan-Meier and Cox proportional hazards regression analysis with time-varying coefficients were used to test the predictive activity of BCI by HoxB13/IL17BR (H/I) status (High vs Low). Likelihood ratio test based on Cox regression was used to evaluate treatment by biomarker interaction. Results: 2637 tumors were centrally assessed for ER, PR and HER2 status leading to 1822 HR+ patients analyzed (1018 N0, 583 N+). Initial results from patients with N+ disease at 12 years of median follow-up showed 287 (49%) were classified as H/I-High and 296 (51%) were classified as H/I-Low. H/I High patients showed a statistically significant benefit of 9.8% in RFI with 10y vs 5y of TAM (HR=0.35 [95% CI 0.15-0.85]; P=0.027), whereas H/I Low patients showed no benefit (-0.2% RFI; HR=1.07 [95% CI 0.69-1.65]; P=0.77). A statistically significant interaction between continuous BCI and treatment was demonstrated (P = 0.02). Conclusions: These data provide further validation and establish level 1B evidence for BCI as a predictive biomarker for preferential benefit from EET in HR+ breast cancer.

Bibliographic note

doi: 10.1200/JCO.2019.37.15_suppl.505

Details

Original languageEnglish
Pages (from-to)505
Number of pages1
JournalJournal of Clinical Oncology
Volume37
Issue number15_suppl
Publication statusPublished - 20 May 2019