Abstract P4-13-04: Estrogen and Avoidance of Invasive Breast Cancer, Coronary Heart Disease and All-cause Mortality. Public Health Impact of Estrogen Guidelines for Women entering Menopause.
Authors: Ragaz J , Wilson K , Shakeraneh S , Budlovsky J , Wong H 
Published: August 2014

Abstract
BACKGROUND. Estrogen [E] for women entering menopause is not perceived beneficial for either iBrCa or CHD. However, data from RCTs suggest that use of Estrogen reduces: a. rates of invasive breast cancer [iBrCa], andb. atherogenesis, vessel pathology and in certain age groups, coronary heart disease [CHD].
OBJECTIVES: To estimate the population-level impact of Estrogen as part of hormone replacement therapy [HRT] for women entering menopause on rates of iBrCa, CHD and all cause mortality [AC- Mort] that could result from a change of Practice where Estrogen would be recommended for women entering menopause.
METHODOLOGY. Annualized rates of iBrCa, CHD and AC-Mort in women age 50–59, and annualized iBrCa rates for all participants and those without Past History of Benign Breast Disease [PHBBD] extracted from the results of the Women's Health Initiative trial [E] alone vs placebo [Refs 1,2], were applied to estimate the reduction in the Number of Avoided Events per 100,000 female population per annum [NAE].
The [NAE] over 10 years follow up was calculated as: NAE = (P − E) × 100,000 × 10 where P was the annualized rate among placebo participants and E was the annualized rate among Estrogen participants.
RESULTS. [Table 1]. Taking 100,000 exposed versus unexposed women age 50–59, and rate reduction due to [E] of −41% [HR=0.59], −20% [HR=0.80] and −27% [HR=0.73] for CHD, iBrCa and AC-Mort [Ref 1,2], respectively, there will be annual avoidance of −130 cases of CHD, −60 of iBrCa, and −130 of deaths from any cause. iBrCa annual avoidance for women any age, and those without PHBBD, were −80 and −150 events, respectively.

CONCLUSION.
1. Estrogen therapy could reduce thousands of BrCa, CHD and AC-Mortality events annually, just in North America. These gains are in addition to the established quality of life improvement for millions of women due to [E]. 2. Of particular importance is the [E] effect on reduction of iBrCa rates, particularly significant for women without PHBBD, confirming the new paradigm of Dual E effect for human BrCa [Ref 3]. 3. These substantial Public Health gains associated with [E] may justify changing policy to incorporate [E] into HRT guidelines for appropriately selected women. 4. Accelerated research to optimize [E] formulations, and identifying subsets that benefit most, is urgently required for optimum HRT use in Prevention of iBrCa, CHD, and reducing AC- mortality.
REFERENCES
1. LaCroix AZ, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA 2011;305:1305–14. 2. Anderson GL, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial Lancet Oncol 2012;13:476–86. 3. Ragaz J, et al. Dual estrogen effects on breast cancer: endogenous estrogen stimulates, exogenous estrogen protects. Further investigation of estrogen chemoprevention is warranted. Cancer Res 2010;70.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-04.