Abstract
Endogenous estrogens have been associated with overall breast cancer risk, particularly for postmenopausal women, and ways to reduce these estrogens have served as a primary means to decrease overall risk. This narrative review of clinical studies details how various nutritional and exercise lifestyle interventions have been used to modify estrogen levels and metabolism to provide a protective impact against breast cancer incidence. We also summarized the evidence supporting the efficacy of interventions, outcomes of interest and identified emerging research themes. A systematic PubMed MEDLINE search identified scholarly articles or reviews published between 2000-2020 that contained either a cohort, cross-sectional, or interventional study design and focused on the relationships between diet and/or exercise and overall levels of different forms of estrogen and breast cancer risk and occurrence. Screening and data extraction was undertaken by two researchers. Data synthesis was narrative due to the heterogeneous nature of studies. A total of 1625 titles/abstracts were screened, 198 full texts reviewed; and 43 met eligibility criteria. Of the 43 studies, 28 were randomized controlled trials, and 15 were observational studies. Overall, studies that incorporated both diet and exercise interventions demonstrated better control of detrimental estrogen forms and levels and thus likely represent the best strategies for preventing breast cancer development for postmenopausal women. Some of the strongest associations included weight loss via diet and diet + exercise interventions, reducing alcohol consumption, and consuming a varied dietary pattern, similar to the Mediterranean diet. More research should be done on the effects of specific nutritional components on endogenous estrogen levels to understand the effect that the components have on their own and in combination within the diet.
Highlights
Breast cancer is the second most common form of cancer in women, with approximately 255,000 new cases diagnosed in the U.S annually, resulting in about 42,000 deaths where Black women die at a higher rate compared to White women [1]
With the studies reviewed it becomes clear that body mass index (BMI) plays an important role in regulating estrogen levels in the body
In a study by McTiernan et al in 2012, researchers found that women with a high BMI in the highest quartile of physical activity had the lowest levels of estrogens while women in the lowest quartile of physical activity from the same BMI range had the highest, indicating that BMI may be an “effect measure modifier” [46]
Summary
Breast cancer is the second most common form of cancer in women, with approximately 255,000 new cases diagnosed in the U.S annually, resulting in about 42,000 deaths where Black women die at a higher rate compared to White women [1]. Other risk factors have an association with estrogen exposure within the body, such as the early onset of menstruation (55 years), using hormone replacement therapy, and having a body mass index (BMI) greater than 30 [2]. In addition to total parent estrogen levels, estrone and estradiol may be irreversibly metabolized through cytochrome P450 enzymes, primarily found in the liver [4] Several of these metabolites have been shown to affect overall breast cancer risk [4]. The cytochrome P450 enzymes CYP1A1, CYP1B1, and CYP1A2 help catalyze these pathways, generating end products that are less potent than the parent estrogen These 2-hydroxylated estrogen metabolites have demonstrated a protective effect against breast cancer development [4]. The 16-hydroxylated metabolites, 16a-hydroxyestrone, have been shown to promote cancer cell growth and proliferation of breast cells in animal models
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