Favorable modulation of benign breast tissue and serum risk biomarkers is associated with >10 % weight loss in postmenopausal women.
ABSTRACT We conducted a phase II feasibility study of a 6-month behavioral weight loss intervention in postmenopausal overweight and obese women at increased risk for breast cancer and the effects of weight loss on anthropomorphic, blood, and benign breast tissue biomarkers. 67 women were screened by random peri-areolar fine-needle aspiration, 27 were registered and 24 participated in the interventional phase. The 24 biomarker evaluable women had a median baseline BMI of 34.2 kg/m(2) and lost a median of 11 % of their initial weight. Significant tissue biomarker modulation after the 6-month intervention was noted for Ki-67 (if restricted to the 15 women with any Ki-67 at baseline, p = 0.041), adiponectin to leptin ratio (p = 0.003); and cyclin B1 (p = 0.001), phosphorylated retinoblastoma (p = 0.005), and ribosomal S6 (p = 0.004) proteins. Favorable modulation for serum markers was observed for sex hormone-binding globulin (p < 0.001), bioavailable estradiol (p < 0.001), bioavailable testosterone (p = 0.033), insulin (p = 0.018), adiponectin (p = 0.001), leptin (p < 0.001), the adiponectin to leptin ratio (p < 0.001), C-reactive protein (p = 0.002), and hepatocyte growth factor (p = 0.011). When subdivided by <10 or >10 % weight loss, change in percent total body and android (visceral) fat, physical activity, and the majority of the serum and tissue biomarkers were significantly modulated only for women with >10 % weight loss from baseline. Some factors such as serum PAI-1 and breast tissue pS2 (estrogen-inducible gene) mRNA were not significantly modulated overall but were when considering only those with >10 % weight loss. In conclusion, a median weight loss of 11 % over 6 months resulted in favorable modulation of a number of anthropomorphic, breast tissue and serum risk and mechanistic markers. Weight loss of 10 % or more should likely be the goal for breast cancer risk reduction studies in obese women.
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ABSTRACT: Despite recent calls to intensify the search for new risk factors for breast cancer, acting on information that we already have could prevent thousands of cases each year. This article reviews breast cancer primary prevention strategies that are applicable to all women, discusses the underutilization of chemoprevention in high-risk women, highlights the additional advances that could be made by including young women in prevention efforts, and comments on how the molecular heterogeneity of breast cancer affects prevention research and strategies. CA Cancer J Clin 2014. © 2014 American Cancer SocietyCA A Cancer Journal for Clinicians 03/2014; 64(3). DOI:10.3322/caac.21225 · 162.50 Impact Factor
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ABSTRACT: The prevalence of obesity, an established risk factor for many chronic diseases including several types of cancer, has risen steadily over the past 4 decades in the US and worldwide. To date, research in this area has focused on the epidemiologic associations between obesity and cancer risk, as well as the mechanisms underlying those associations. However, an emerging but understudied issue of clinical importance is the diminution of chemotherapeutic efficacy in obese cancer patients. The mechanisms underlying the negative impact of obesity on therapeutic responses are likely multifactorial. The effect of obesity on chemotherapy drug pharmacokinetics and dosage has been extensively reviewed elsewhere, so this review will focus on the interplay between obesity, increased inflammation, metabolic perturbations and chemoresistance. The ultimate goal of this review is to delineate areas for future research that could lead to the identification of new targets and strategies for improved cancer outcomes in obese patients.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 24 June 2014; doi:10.1038/clpt.2014.136.Clinical Pharmacology & Therapeutics 06/2014; 96(4). DOI:10.1038/clpt.2014.136 · 7.39 Impact Factor
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ABSTRACT: Obesity and low levels of physical activity are associated with a higher risk of breast cancer recurrence and mortality. Currently, over 65 % of breast cancer survivors are overweight or obese, and fewer than 30 % engage in recommended levels of physical activity. The reason for low adherence to lifestyle guidelines is likely multifactorial. Given the continuing trend of increased obesity and physical inactivity in the United States, worldwide and in breast cancer survivors, more research showing the direct effect of weight loss and/or exercise on breast cancer recurrence and mortality is needed. Many exercise interventions have examined the impact of increasing exercise on changes in quality of life, with most studies showing a favorable effect of exercise on quality of life. Smaller Phase II randomized trials using biomarkers as surrogate endpoints is likely appropriate to answer questions regarding mechanisms of action, exercise type, volume, and intensity, yet a definitive trial of weight loss and exercise on disease-free survival is critical for moving the field forward. Research is also necessary on how to disseminate lifestyle interventions into the clinic and community that lead to clinically meaningful weight losses of at least 5 % that are maintained over time, and favorable sustained changes in physical activity levels. Changes in referrals, access, and reimbursement of lifestyle programs may lead to favorable changes in the prevalence of obesity and physical activity in breast cancer survivors and in turn rates of breast cancer recurrence and mortality.Advances in Experimental Medicine and Biology 01/2015; 862:193-212. DOI:10.1007/978-3-319-16366-6_13 · 2.01 Impact Factor