Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk

Abstract

IMPORTANCE Over ⅔ of U.S. women are overweight or obese, placing them at increased risk for postmenopausal breast cancer. OBJECTIVE To investigate the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended follow-up in the Women’s Health Initiative (WHI) Clinical Trial. DESIGN The WHI protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer endpoints. SETTING 40 U.S. clinical centers. PARTICIPANTS n=67,142 postmenopausal women aged 50–79 years were enrolled from 1993–1998 with a median of 13 years of follow-up through 2010; 3388 invasive breast cancers were observed. MAIN OUTCOMES AND MEASURES Height and weight were measured at baseline and weight was measured annually thereafter. Data were collected on demographic characteristics, personal and family medical history and personal habits (smoking, physical activity). Women underwent annual or biennial mammograms. Breast cancers were verified by medical records reviewed by physician adjudicators. RESULTS Women who were overweight and obese had an increased invasive breast cancer risk vs. normal weight women. Risk was greatest for obesity grades 2+3 (BMI>35.0 kg/m2) (hazard ratio [HR] for invasive breast cancer =1.58, 95% CI 1.40–1.79). BMI ≥ 35.0 kg/m2 was strongly associated with risk for ER+/PR+ breast cancers (HR=1.86 95% CI 1.60–2.17), but was not associated with ER− cancers. Obesity grade 2+3 was also associated with advanced disease including larger tumor size (HR=2.12 95%CI 1.67–2.69). (P=0.02), positive lymph nodes (HR=1.89 95%CI 1.46–2.45), (P=0.06), regional/distant stage (HR=1.94, 95%CI 1.52–2.47) (P=0.05) and deaths after breast cancer (HR=2.11 95%CI 1.57–2.84) (P<0.001). Women with baseline BMI<25.0 kg/m2 who gained >5% of bodyweight over the follow-up period had an increased breast cancer risk (HR=1.36 95% CI 1.1–1.65), but among women already overweight or obese we found no association of weight change (gain or loss) with breast cancer during follow-up. There was no effect modification of the BMI-breast cancer relationship by postmenopausal hormone therapy (HT) and the direction of association across BMI categories was similar for never, past and current HT use. CONCLUSIONS/RELEVANCE Obesity is associated with increased invasive breast cancer risk in postmenopausal women. These clinically meaningful findings should motivate programs for obesity prevention.

Joint relative risks for estrogen receptor-positive breast cancer from a clinical model, polygenic risk score, and sex hormones

“…We examined hormones without adjustment for covariates to determine whether they improved the prediction of our models. For example, we did not adjust for BMI because the relationship between obesity and breast cancer risk is primarily mediated through its effect on circulating estrogen levels [34–36]. Supporting this assumption, adjusting for BMI in secondary analyses minimally attenuated the association between estradiol and ER-positive breast cancer.…”

The Protective Effect of Amphimas pterocarpoides Plant Extract on Bone Mineral Density and Strength in Estrogen Deficient Ovariectomized Wistar Rats

“…Weight gain, with abdominal predominance, is a well known consequence of menopause, is related to estrogen deficiency and probably mediated by the decreased production of estradiol and the subsequent lack of ERα activation [40,41]. Even though obesity seems to protect bones by stimulating neoformation, it remains an unwanted effect due to its implication in the development of cardiovascular disease or cancer [42,43]. The AP extract in the present dose failed to inhibit the rise in body weight in our study, but this might be a doserelated effect.…”

Why Are Women with Obesity More Likely to Develop Breast Cancer

“…At a macro level, researchers use experimental and clinical data to examine multiple demographic characteristics of obesity related to breast cancer. A clinical trial was conducted, showing that postmenopausal women with BMI >35 kg/m 2 at US clinical centers were more likely to develop invasive breast cancer [20]. Recently, Park et al investigated the risks of metabolic disorder and obesity phenotypes in breast cancer participants 35-74 years in age [21].…”