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Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials.
JAMA Oncol 2015; 1(5):611-21JO

Abstract

IMPORTANCE

More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer.

OBJECTIVE

To investigate in this secondary analysis 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 trials.

DESIGN, SETTING, AND PARTICIPANTS

The WHI clinical trial protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer end points in 67 142 postmenopausal women ages 50 to 79 years at 40 US clinical centers. The women were enrolled from 1993 to 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 women of normal weight. Risk was greatest for obesity grade 2 plus 3 (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >35.0) (hazard ratio [HR] for invasive breast cancer, 1.58; 95% CI, 1.40-1.79). A BMI of 35.0 or higher was strongly associated with risk for estrogen receptor-positive and progesterone receptor-positive breast cancers (HR, 1.86; 95% CI, 1.60-2.17) but was not associated with estrogen receptor-negative cancers. Obesity grade 2 plus 3 was also associated with advanced disease, including larger tumor size (HR, 2.12; 95% CI, 1.67-2.69; P = .02), positive lymph nodes (HR, 1.89; 95% CI, 1.46-2.45; P = .06), regional and/or distant stage (HR, 1.94; 95% CI, 1.52-2.47; P = .05), and deaths after breast cancer (HR, 2.11; 95% CI, 1.57-2.84; P < .001). Women with a baseline BMI of less than 25.0 who gained more than 5% of body weight 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, and the direction of association across BMI categories was similar for never, past, and current hormone therapy use.

CONCLUSIONS AND RELEVANCE

Obesity is associated with increased invasive breast cancer risk in postmenopausal women. These clinically meaningful findings should motivate programs for obesity prevention.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00000611.

Authors+Show Affiliations

Division of Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.Division of Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.Division of Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Los Angeles Biomedical Research Institute at Harbor-UCLA, David Geffen School of Medicine, University of California, Los Angeles.Department of Medicine, George Washington University School of Medicine, Washington, DC.Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York.Division of Health Promotion Sciences, University of Arizona, Tucson/Phoenix.Division of Research, Kaiser Permanente, Oakland, California.Division of Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill.Division of Reproductive Endocrinology and Fertility, University of Texas Health Science Center, San Antonio.Division of Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

26182172

Citation

Neuhouser, Marian L., et al. "Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: a Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials." JAMA Oncology, vol. 1, no. 5, 2015, pp. 611-21.
Neuhouser ML, Aragaki AK, Prentice RL, et al. Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials. JAMA Oncol. 2015;1(5):611-21.
Neuhouser, M. L., Aragaki, A. K., Prentice, R. L., Manson, J. E., Chlebowski, R., Carty, C. L., ... Anderson, G. L. (2015). Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials. JAMA Oncology, 1(5), pp. 611-21. doi:10.1001/jamaoncol.2015.1546.
Neuhouser ML, et al. Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: a Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials. JAMA Oncol. 2015;1(5):611-21. PubMed PMID: 26182172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials. AU - Neuhouser,Marian L, AU - Aragaki,Aaron K, AU - Prentice,Ross L, AU - Manson,JoAnn E, AU - Chlebowski,Rowan, AU - Carty,Cara L, AU - Ochs-Balcom,Heather M, AU - Thomson,Cynthia A, AU - Caan,Bette J, AU - Tinker,Lesley F, AU - Urrutia,Rachel Peragallo, AU - Knudtson,Jennifer, AU - Anderson,Garnet L, PY - 2015/7/17/entrez PY - 2015/7/17/pubmed PY - 2016/4/1/medline SP - 611 EP - 21 JF - JAMA oncology JO - JAMA Oncol VL - 1 IS - 5 N2 - IMPORTANCE: More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer. OBJECTIVE: To investigate in this secondary analysis 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 trials. DESIGN, SETTING, AND PARTICIPANTS: The WHI clinical trial protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer end points in 67 142 postmenopausal women ages 50 to 79 years at 40 US clinical centers. The women were enrolled from 1993 to 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 women of normal weight. Risk was greatest for obesity grade 2 plus 3 (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >35.0) (hazard ratio [HR] for invasive breast cancer, 1.58; 95% CI, 1.40-1.79). A BMI of 35.0 or higher was strongly associated with risk for estrogen receptor-positive and progesterone receptor-positive breast cancers (HR, 1.86; 95% CI, 1.60-2.17) but was not associated with estrogen receptor-negative cancers. Obesity grade 2 plus 3 was also associated with advanced disease, including larger tumor size (HR, 2.12; 95% CI, 1.67-2.69; P = .02), positive lymph nodes (HR, 1.89; 95% CI, 1.46-2.45; P = .06), regional and/or distant stage (HR, 1.94; 95% CI, 1.52-2.47; P = .05), and deaths after breast cancer (HR, 2.11; 95% CI, 1.57-2.84; P < .001). Women with a baseline BMI of less than 25.0 who gained more than 5% of body weight 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, and the direction of association across BMI categories was similar for never, past, and current hormone therapy use. CONCLUSIONS AND RELEVANCE: Obesity is associated with increased invasive breast cancer risk in postmenopausal women. These clinically meaningful findings should motivate programs for obesity prevention. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611. SN - 2374-2445 UR - https://www.unboundmedicine.com/medline/citation/26182172/Overweight_Obesity_and_Postmenopausal_Invasive_Breast_Cancer_Risk:_A_Secondary_Analysis_of_the_Women's_Health_Initiative_Randomized_Clinical_Trials_ L2 - https://jamanetwork.com/journals/jamaoncology/fullarticle/10.1001/jamaoncol.2015.1546 DB - PRIME DP - Unbound Medicine ER -