Abstract P6-13-06: Estrogen-based hormone replacement [HRT] therapy is substantially more effective than tamoxifen in reducing breast cancer mortality and breast cancer case fatality ratio: Emergence of a new paradigm

Abstract

Abstract OBJECTIVE: To compare, in the setting of breast cancer (BrCa) prevention, the impact of estrogen-based hormone replacement therapy (E-HRT) vs. tamoxifen (TAM) on breast cancer mortality (BrCa-M) and breast cancer case fatality ratio (BrCa-CFR), by analyzing data from the Women's Health Initiative Trial 2 (WHI HRT Trial 2, E-HRT vs. placebo [P])1 and the International Breast Cancer Intervention Study 1 (IBIS-1), TAM vs. P.2 METHODS: Hazard ratios (HR) and confidence intervals (CI) for BrCa incidence and mortality were extracted from the original WHI HRT Trial 2 and IBIS-1 trials.1,2 BrCa-CFRs were estimated by dividing the mortality HR by the incidence HR. Subsequently, to compare E-HRT vs. TAM outcomes, the ratios of HRs (HR1/HR2) between the two trials were estimated separately for BrCa-M and BrCa-CFR. The 95% CI was derived through logarithmic transformation of the 95% CI originally reported. RESULTS: Mortality and Case Fatality Outcomes: Impact of E-HRT versus TAM, expressed as ratio of HRs E-HRT vs. Placebo, HR1TAM vs. Placebo, HR2HR1/HR2pMortality0.55 (0.33-0.92)1.19 (0.68-2.10)0.46 (0.22-0.99)0.046Case Fatality0.70 (0.40-1.20)1.68 (0.93-3.01)0.42 (0.18-0.94)0.040 CONCLUSIONS: While acknowledging between-trial comparisons including eligibility differences, E-HRT yields significant reductions in BrCa mortality and case fatality as compared with TAM (54% and 58% respectively). These unexpected breast cancer mortality reductions represent major public health gains, additional to the already known superiority of E-HRT over TAM in terms of skeletal fracture rates and Alzheimer's dementia mortality reduction, and, in women entering menopause, also of cardiac and all-cause mortality reductions. REFERENCES: 1. Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials. JAMA 2017;318:927-38. 2. Cuzick J, Sestak I, Cawthorn S, et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. The Lancet Oncology 2015;16:67-75. Citation Format: Ragaz J, Shakeraneh S, Qian H, Wilson KS, Wong H, Spinelli JJ. Estrogen-based hormone replacement [HRT] therapy is substantially more effective than tamoxifen in reducing breast cancer mortality and breast cancer case fatality ratio: Emergence of a new paradigm [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-13-06.