138MO - Prognostic performance of Breast Cancer Index (BCI) in postmenopausal women with early-stage HR+ breast cancer in the TEAM trial

Background

Early-stage HR+ breast cancer patients face a prolonged risk of recurrence even after adjuvant endocrine therapy. The Breast Cancer Index (BCI) and BCIN+ prognostic models are significantly prognostic for risk of overall (0-10y) and late (5-10y) distant recurrence (DR) in N0 and N1 breast cancer, respectively. Here, the prognostic performance of BCI and BCIN+ was evaluated in a cohort of HR+ postmenopausal women from the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial.

Methods

BCI testing was performed blinded to clinical outcome with BCI/BCIN+ risk groups calculated based on pre-specified cut-points. Kaplan-Meier analysis and log-rank test were used to assess the prognostic significance of BCI/BCIN+ risk groups based on DR. Cox proportional hazard models with and without clinical covariates were used to estimate hazard ratios (HRs) and the associated 95% confidence intervals (CIs).

Results

1520 HR+ N0 and 2249 N1 patients were included. For overall 10y DR, BCI stratified 1197 N0 patients who did not receive chemotherapy into three prognostic groups: 47% low-, 29% intermediate- and 24% high-risk. BCIN+ stratified 1319 N1 patients into two groups: 23% low- and 77% high-risk. In the 3053 patients who were DR-free for 5 years, the 10-year late DR rates for low- and high-risk were 5.4% (95%CI: 3.0%-7.8%) and 9.3% (95%CI: 6.7%-11.8%) in the N0 cohort (N= 1285) and 5.5% (95%CI: 2.9%-8.0%) and 12.2% (95%CI: 10.2%-14.1%) in the N1 cohort (N= 1768). Similarly, significant prognostic results were observed in the multivariate analysis adjusting for age, tumor size, grade, treatment as well as in HER2- patients (Table). Table: 138MO

Conclusions

BCI and BCIN+ are significantly prognostic for risk of overall DR (0-10y) and late DR (5-10y) for N0 and N1 patients, respectively. These results provide further validation of BCI clinical utility as an aid in the decision-making for adjuvant therapies for HR+ breast cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Biotheranostics, Inc., a Hologic Company.

Funding

Biotheranostics, Inc., a Hologic Company.

Disclosure

J.M. Bartlett: Financial Interests, Personal, Other, Honoraria: Nanostring Technologies, Inc., Oncology Education, Biotheranostics, A Hologic Company, MedcomXchange, Communications Inc; Financial Interests, Personal, Advisory Role: Insight Genetics, Inc., BioNTech AG, Biotheranostics, A Hologic Company, Pfizer, Rna Diagnostics Inc, oncoXchange/MedcomXchange Communications Inc., Herbert Smith French Solicitors, OncoCyte Corporation; Financial Interests, Personal, Funding: Thermo Fisher Scientific, Genoptix, Agendia, NanoString Technologies, Inc., Stratifyer GmbH, Biotheranostics, A Hologic Company; Financial Interests, Personal, Other, Patents - Jan 2017: Methods and Devices for Predicting Anthracycline Treatment Efficacy, US utility – 15/325,472; EPO – 15822898.1; Canada – not yet assigned Jan 2017: Systems, Devices and Methods for Constructing and Using a Biomarker, US utility – 15/328,108; EPO – 15824751.0; Canada – not yet assigned Oct 2016: Histone gene module predicts anthracycline benefit, PCT/CA2016/000247 Dec 2016: 95-Gene Signature of Residual Risk Following Endocrine Treatment, PCT/CA2016/000304 Dec 2016: Immune Gene Signature Predicts Anthracycline Benefit, PCT/CA2016/000305 June 2020: Use of Molecular Classifiers to Diagnose, Treat and Prognose Prostate Cancer, US Provisional 63/040.692, Disclosure Name: A Molecular Classifier for Personalized Risk Stratification for Patients with Prostate Cancer, Date: 21/08/2019: Other - Patents; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Biotheranostics, A Hologic Company, NanoString Technologies, Inc., Breast Cancer Society of Canada. J. Wong: Financial Interests, Personal, Full or part-time Employment: Biotheranostics, A Hologic Company; Financial Interests, Personal, Stocks/Shares: Biotheranostics, A Hologic Company; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Biotheranostics, A Hologic Company. G. Pond: Financial Interests, Personal, Other, Honoraria: Astra-Zeneca, Takeda; Financial Interests, Personal, Advisory Role: Merck, Profound Medical; Financial Interests, Personal, Stocks/Shares: Roche Ltd. Y. Zhang: Financial Interests, Personal, Full or part-time Employment: Biotheranostics, A Hologic Company; Financial Interests, Personal, Stocks/Shares: Biotheranostics, A Hologic Company; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Biotheranostics, A Hologic Company; Financial Interests, Personal, Other, Patents: Predicting likelihood of response to combination therapy, Registered United States of America Application no: 14/724,732 Application date: 5/28/2015 Registration No: 10,253,369 Registration date: 4/9/2019; Integration of tumor characteristics with breast cancer index, pending united States of America Application no: 15/349,915 Application date: 11/11/2016; Predicting breast cancer recurrence; Pending United States of America Application no: 14/483,108 Application date: 9/10/2014; Post-treatment breast cancer prognosis, Pending United States of America Application no: 15/298,128 Application date: 10/19/2016; Neuroendocrine tumors, Pending United States of America Application no: 15/656,998 Application date: 7/21/2017: Biotheranostics, A Hologic Company. R. Salunga: Financial Interests, Personal, Full or part-time Employment: Biotheranostics, A Hologic Company; Financial Interests, Personal, Stocks/Shares: Biotheranostics, A Hologic Company; Financial Interests, Institutional, Funding: Biotheranostics, A Hologic Company. C. Markopoulos: Financial Interests, Personal, Advisory Role: Exact Sciences. D. Rea: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Advisory Role: Genomic Health, MSD Oncology; Financial Interests, Institutional, Funding: Celgene, Roche, Biotheranostics, A Hologic Company; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Daiichi Sankyo, Eisai, Novartis, Pfizer. C.A. Schnabel: Financial Interests, Personal, Full or part-time Employment: Biotheranostics, A Hologic Company; Financial Interests, Personal, Stocks/Shares: Biotheranostics, A Hologic Company; Financial Interests, Personal, Officer: Biotheranostics, A Hologic Company; Financial Interests, Personal, Other, Patents: Predicting likelihood of response to combination therapy, Registered United States of America Application no: 14/724,732 Application date: 5/28/2015 Registration No: 10,253,369 Registration date: 4/9/2019; Integration of tumor characteristics with breast cancer index, Pending United States of America Application no: 15/349,915 Application date: 11/11/2016; Predicting breast cancer recurrence; pending united states of america application no: 14/483,108 Application date: 9/10/2014; Post-treatment breast cancer prognosis, pending united states of america application no: 15/298,128 Application date: 10/19/2016; Neuroendocrine tumors, Pending United States of America Application no: 15/656,998 Application date: 7/21/2017: Biotheranostics, A Hologic Company; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Biotheranostics, A Hologic Company. K. Treuner: Financial Interests, Personal, Full or part-time Employment: Biotheranostics, A Hologic Company; Financial Interests, Personal, Stocks/Shares: Biotheranostics, A Hologic Company; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Biotheranostics, A Hologic Company; Financial Interests, Personal, Leadership Role: Biotheranostics, A Hologic Company. J. Bayani: Financial Interests, Personal, Other, Honoraria: Thermo Fisher Scientific, NanoString Technologies; Financial Interests, Personal and Institutional, Research Grant: Thermo Fisher Scientific. All other authors have declared no conflicts of interest.