Abstract P6-09-09: Dual Estrogen Effects on Breast Cancer: Endogenous Estrogen Stimulates, Exogenous Estrogen Protects. Further Investigation of Estrogen Chemoprevention Is Warranted

Abstract

Abstract Introduction Until the randomized Women Healths Initiative [WHI] trials 1,2, most hormone replacement therapy (HRT) studies showed an association of HRT with higher BrCa risk. However, our recent reviews of the WHI trials suggested that Estrogen alone can be protective while HRT based on Estrogen + Progestin can be carcinogenic 3, 4. In this analysis, we expand this concept to examine the difference between “Exogenous” Estrogen — delivered as part of HRT, versus “Endogenous” Estrogen — i.e. E produced by human tissues. Rationale 1: Endogenous E is carcinogenic. Reducing E levels through oophorectomy, selective oestrogen receptor modulators (SERMs) or with aromatase inhibition is effective at all stages of oestrogen receptor positive breast cancer and is significantly protective against BrCa in high risk women 5. Rationale 2: Exogenous E Protective: Updates of the WHI trial 2 [women with hysterectomy, randomized to E alone versus Placebo, 1,2 ] with analyses according to prior history of Benign Breast Disease (PH BrD); a first degree relative with BrCa (PH 1st Rel BrCa); or prior HRT use, show: Results of the WHI trial 2 CONCLUSIONS These data are compatible with a dual estrogen effect where Exogenous Estrogen is protective, in contrast to the carcinogenic impact of Endogenous Estrogen. The protective effect of Estrogen is comparable in magnitude to that reported with tamoxifen in high risk women. Based on these data, we propose that: 1. In selected women - [i.e. the majority of the WHI HRT trial 2 participants, 71.5 - 80%] - the use of HRT based on Estrogens alone may be appropriate to manage menopausal symptoms, as it is associated with a significant reduction of BrCa rates. 2. The use of Exogenous Estrogen in chemoprevention merits validation, with the optimum Estrogen regimen determination [type of Estrogens; dose; mode of delivery, etc.] high priority.