Estrogens and breast cancer: Mechanisms involved in obesity-related development, growth and progression

Abstract

Obesity is a risk factor for estrogen receptor-positive (ER+) breast cancer after menopause. The pro-proliferative effects of estrogens are well characterized and there is a growing body of evidence to also suggest an important role in tumorigenesis. Importantly, obesity not only increases the risk of breast cancer, but it also increases the risk of recurrence and cancer-associated death. Aromatase is the rate-limiting enzyme in estrogen biosynthesis and its expression in breast adipose stromal cells is hypothesized to drive the growth of breast tumors and confer resistance to endocrine therapy in obese postmenopausal women. The molecular regulation of aromatase has been characterized in response to many obesity-related molecules, including inflammatory mediators and adipokines. This review is aimed at providing an overview of our current knowledge in relation to the regulation of estrogens in adipose tissue and their role in driving breast tumor development, growth and progression.

Factors Affecting Nodal Status in Breast Cancer

“…The effects of estrogens proliferation help the growth of body is evidence of the important role in tumor genesis. Importantly, obesity not causes breast cancer, but it associated with other factors such as loco-regional recurrence, metastasis of axillary nodes and cancer-associated death [15] Also, Picon-Ruiz and colleagues carried a study between 2011 and 2014, in the United States, and reported that, obesity had been associated with premature menopause and premature menopause increased the risk of breast cancer [16] . Guldberg and colleagues also revealed that, premenopausal breast cancer women who are overweight and have poorer physical function have poorer prognosis [17] .…”

Obesity, estrogens and adipose tissue dysfunction – implications for pulmonary arterial hypertension

“…After menopause, adipose tissue is the primary source of estrogen production in the body. 6 Adipose tissue interconverts stored or circulating sex steroids but does not synthesis sex steroids de novo. Circulating C19 steroid precursors androstenedione, dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) act as a reservoir for extragonadal estrogen synthesis.…”

Endocrine Therapy-related Endocrinopathies—Biology, Prevalence, and Implications for the Management of Breast Cancer

“…4 After menopause, the adipose tissue, including that of the breast, is the main site of estrogen production. 5,6 Estrogens are also synthesized in the bone, joints, and brain. 5 In these women, aromatase inhibitors are effective at suppressing aromatase throughout the body, thus profoundly decreasing estrogen levels both locally and systemically.…”

“…Candidates include insulin and glucose, as well as inflammatory mediators and estrogens produced locally in the breast adipose tissue. 6,[66][67][68] Some tumors rely heavily on glucose as a source of energy and, as a result, display enhanced glucose uptake and metabolism. 69 This is the basis of 18 F-fluorodeoxyglucose positron emission tomography, whereby a non-metabolizable glucose tracer is used to image cancer metastases.…”