Obesity and Breast Cancer: The Estrogen Connection

Abstract

There is now substantial evidence that overweight and/or obesity and/or weight gain are risk factors for the development of postmenopausal breast cancer. In addition, obesity and/or elevated body mass index at breast cancer diagnosis has a negative impact on prognosis for both premenopausal and postmenopausal women. Therefore, understanding the mechanism of how obesity affects the mammary tumorigenesis process is an important health issue. Elevated serum estrogen levels as well as enhanced local production of estrogen have been considered primary mediators of how increased body weight promotes breast cancer development in postmenopausal women. Here, we provide an overview of estrogen's relationship with both obesity and breast cancer as separate entities. Human and relevant preclinical studies are cited. In addition, other growth factors that may be involved in this relationship are considered.

Mesenchymal stem cells in mammary adipose tissue stimulate progression of breast cancer resembling the basal-type

“…1,2 Even though adipose tissue is the most abundant stromal constituent in the breast, little is known about the involvement of resident adipose-derived cells in the development of breast cancer. 3 Increased adiposity and obesity are associated with an elevated risk of developing the most prevalent form of breast cancer (luminal type A) in post-menopausal women, [4][5][6] an association assumed to be largely due to adipose tissue being a primary Data are accumulating to support a role for adipose-derived mesenchymal stem cells (MsCs) in breast cancer progression; however, to date most studies have relied on adipose MsCs from non-breast sources. There is a particular need to investigate the role of adipose MsCs in the pathogenesis of basal-like breast cancer, which develops at a disproportionate rate in pre-menopausal african-american women with a gain in adiposity.…”

Obesity and Cancer: Concepts and Challenges

“…Obesity has been associated with higher breast cancer risk across observational studies, meta-analyses, and systematic reviews in different populations, especially for estrogen receptor positive breast cancer in postmenopausal women [25,[36][37][38][39]. Additional evidence suggests that obese women are also at increased risk for development of triple-negative breast cancer compared to the non-obese [40].…”

Physical Activity and Genitourinary Cancer Survivorship

“…In a pooled analysis of nine prospective studies in postmenopausal women (Key et al 2002), the odds ratio for breast cancer was 2.00 (95% CI: 1.47-2.71) for the highest versus the lowest quintiles of total estradiol while for estrone the odds ratio was 2.19 (95% CI: 1.48-3.22). Given these findings and others (Cleary and Grossmann 2009), it is now widely accepted that estrogen status is associated with postmenopausal breast cancer. Fewer studies have examined this association in premenopausal women given the complexities of studying circulating hormone levels amidst menstrual cycles, and findings in general have been less consistent than for postmenopausal women (Eliassen and Hankinson 2008).…”

“…Hence, by reducing body fat through exercise, estrogen levels may decrease resulting in a lower risk of breast cancer. Levels of adipokines that influence estrogen biosynthesis can also be altered with weight loss (Cleary and Grossmann 2009). Furthermore, physical activity can lower blood insulin levels thereby increasing circulating sex hormone binding globulin (SHBG) (Kaaks 1996;Pugeat et al 1991) which binds reversibly to estrogens to affect their bioavailability.…”