An analysis of extended follow-up data from the Women’s Health Initiative clinical trials suggests that postmenopausal women who were overweight and obese had an increased risk of invasive breast cancer compared to women of normal weight, according to an article published by JAMA Oncology (2015; doi:10.1001/jamaoncol.2015.1546).

Obesity is a major public health problem in the United States. It has been associated with breast cancer risk in observational studies, systematic reviews, and meta-analyses. However, questions remain.

Marian L. Neuhouser, PhD, RD, of the Fred Hutchison Cancer Research Center in Seattle, Washington, and coauthors examined the association between being overweight and obese with the risk of postmenopausal invasive breast cancer. The Women’s Health Initiative (WHI) protocol measured height and weight, baseline and annual or biennial mammography, and breast cancer in 67,142 postmenopausal women enrolled from 1993 to 1998 with a median of 13 years of follow-up. There were 3,388 invasive breast cancers.

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Women who were overweight (body mass index [BMI] 25 to <30); obese, grade 1 (BMI 30 to <35); and obese, grade 2 plus 3 (BMI >35) had an increased risk of invasive breast cancer compared to women of normal weight (BMI <25). The risk was greatest for women with a BMI greater than 35; those women had a 58% increased risk of invasive breast cancer compared with women of normal weight.

A BMI of 35 or higher was associated with increased risk of estrogen and progesterone receptor-positive breast cancer but not estrogen receptor-negative cancers.

Obesity was associated with markers of poor prognosis. Women with a BMI greater than 35 were more likely to have large tumors, evidence of lymph node involvement and poorly differentiated tumors.

Women with a baseline BMI of less than 25 who gained more than 5% of body weight during the follow-up period had an increased risk of breast cancer.

Among women who were already overweight or obese, weight change, whether gain or loss, had no association during follow-up.

Postmenopausal hormone therapy did not affect the relationship between BMI and breast cancer.

“Obesity is associated with a dose-response increased postmenopausal breast cancer risk, particularly for estrogen receptor- and progesterone receptor-positive disease, but risk does not vary by hormone therapy use or race/ethnicity. These clinically meaningful findings support the need for clinical trials evaluating the role of obesity prevention and treatment on breast cancer risk,” concluded the article.

In a related commentary (doi:10.1001/jamaoncol.2015.1547), Clifford Hudis, MD, of Memorial Sloan Kettering Cancer Center, and Andrew Dannenberg, MD, of the Weill Cornell Medical College, both in New York, New York, wrote: “Overweight and obesity are a growing global challenge and the increased burden of malignant disease, to which it contributes, is another one. Their report helps focus our thinking and motivates us to pursue a deeper understanding of why overweight and obesity are a problem so that we can plan more effective and thoughtful responses.”