Circulatory Estrogen Level Protects Against Breast Cancer in Obese Women

Zsuzsanna Suba

doi:10.2174/1574892811308020004

Abstract

Literary data suggest apparently ambiguous interaction between menopausal status and obesity-associated breast cancer risk based on the principle of the carcinogenic capacity of estrogen. Before menopause, breast cancer incidence is relatively low and adiposity is erroneously regarded as a protective factor against this tumor conferred by the obesity associated defective estrogen-synthesis. By contrast, in postmenopausal cases, obesity presents a strong risk factor for breast cancer being mistakenly attributed to the presumed excessive estrogen-production of their adipose-tissue mass. Obesity is associated with dysmetabolism and endangers the healthy equilibrium of sexual hormone-production and regular menstrual cycles in women, which are the prerequisites not only for reproductive capacity but also for somatic health. At the same time, literary data support that anovulatory infertility is a very strong risk for breast cancer in young women either with or without obesity. In the majority of premenopausal women, obesity associated insulin resistance is moderate and may be counteracted by their preserved circulatory estrogen level. Consequently, it is not obesity but rather the still sufficient estrogen-level, which may be protective against breast cancer in young adult females. In obese older women, never using hormone replacement therapy (HRT) the breast cancer risk is high, which is associated with their continuous estrogen loss and increasing insulin-resistance. By contrast, obese postmenopausal women using HRT, have a decreased risk for breast cancer as the protective effect of estrogen-substitution may counteract to their obesity associated systemic alterations. The revealed inverse correlation between circulatory estrogen-level and breast cancer risk in obese women should advance our understanding of breast cancer etiology and promotes primary prevention measures. New patents recommend various methods for the prevention and treatment of obesity-related systemic disorders and the associated breast cancer.

Highlights

Many studies support an apparently Janus-faced ambiguous interaction between obesity and breast cancer risk depending on the menopausal status of patients [1,2,3]
In postmenopausal cases, in the elderly, the association is highly positive, obesity confers a strong risk for breast cancer [2, 6]
Excessive EGF predominance decreased both ER- protein concentration and gene transcription activity in the human breast cancer cell line MCF-7 [116]. These results suggest rather an alternative role of estrogen and growth factor actions in tumor cell proliferation

Summary

Introduction

Many studies support an apparently Janus-faced ambiguous interaction between obesity and breast cancer risk depending on the menopausal status of patients [1,2,3]. Controversial results of clinical studies mistakenly suggest that obesity is advantageous against breast cancer by the defective estrogen synthesis in young women [1]. This assumption seems to be consistent with an inverse relationship between the BMI and serum estradiol levels found in premenopausal cases, in the follicular phase of the cycle [7]. Postmenopausal obesity is harmful by the erroneously presumed excessive estrogen production of adipose tissue mass in older women [8,9,10]

Objectives

Conclusion