Body Fat and Risk of Breast Cancer in Postmenopausal Women: What Is the Truth?

Excerpt

Body fat has been connected with breast cancer risk in postmenopausal women with normal body mass index (BMI) [1]. A persistent association between higher trunk fat and increased risk of estrogen receptor (ER)–positive breast cancer has been found in women who remained in the normal BMI range during the follow-up period [1]. However, it is still unknown because excess adiposity is linked to increased risk in women with a normal BMI [1]. Moreover, the role of fat loss interventions and anti-estrogen therapy for breast cancer risk reduction in postmenopausal women with normal BMI and high body fat levels is not well-defined [1]. Obesity is related to an increased risk of breast cancer, including the ER–positive subtype in postmenopausal women [1]. Obesity has been shown to down-regulate the expression of microRNA-126 (miR-126) [2]. miR-126 has been proposed to act as a tumor suppressor in breast cancer growth and metastasis [3]. It has been reported that miR-126 expression is markedly down-regulated in human breast cancer tissues when compared with adjacent normal tissues [3]. Overexpression of miR-126 has been demonstrated to inhibit the invasion of breast cancer cell lines in vitro [3]. In healthy post-menopausal women, the serum levels of miR-126-3p have been detected to be much lower than that in healthy young women suggesting that 17β-estradiol (E2) may regulate miR-126 -3p in physiological status [4]. miR-126 has emerged to be the direct target of estrogens in human endothelial cells [5]. E2 has been demonstrated to enhance miR-126-3p expression via up-regulation of Ets-1 [5]. Ets-1 represents the well-known transcription factor driving miR-126 expression [4]. Ets-1 transcription factor overexpression in breast cancers has been correlated with invasiveness and a poor prognosis by driving carcinoma cell invasion [5]. Ets-1 has been found to play a critical role in coordinating multiple invasive features of cancer cells [5]. Taken together, I suppose that estrogens seemingly play contradictory actions in breast cancer. On one hand, estrogens appears to reduce the chance of developing breast cancer by up-regulating miR-126 and, on the other hand, they seem to be directly involved in breast tumorigenesis by overexpression of Ets-1. Mechanistically, I hypothesize the existence of a negative-feedback loop between miR-126 expression and Ets-1-induced breast cancer. Further research examining the effect of estrogens, miR-126 and Ets-1 on breast cancer risk appears to be warranted among postmenopausal women. I suggest that fat loss interventions via physical activity and dietary management should represent a reasonable strategy for preventing breast cancer in postmenopausal women taking into account the impact of high body fat levels and the apparently contradictory actions of estrogens on cancer development. …