Avoiding adult weight gain may contribute to the prevention of breast cancer after menopause, particularly among women who do not use postmenopausal hormones, according to a recent article in the The Journal of the American Medical Association (JAMA).

Zhiping Huang, M.D., of the Harvard School of Public Health in Boston, Mass., and colleagues followed 95,256 of the participants in the Nurses Health Study over 16 years to identify modifiable risk factors for breast cancer, a major cause of death among women.

The researchers estimate that as much as a third (34 percent) of new cases of postmenopausal breast cancer is caused by hormone replacement therapy, adult weight gain or both. One out of six postmenopausal breast cancers (16 percent) may be preventable by maintaining weight within four to five pounds after the age of 18.

Among the female nurses in the study, the researchers found a total of 2,517 women with invasive breast cancers, 1,000 premenopausal and 1,517 postmenopausal. They found that obesity and weight gain had diverging effects on premenopausal and postmenopausal breast cancer. Before menopause, the researchers note that obesity appears to reduce the incidence of breast cancer but not death. After menopause, however, adult weight gain increases the risk of both the development of breast cancer and death.

The researchers found women who gained between 44 to 55 pounds after age 18 years were at 40 percent higher risk for developing breast cancer than women who fluctuated only four to five pounds in adulthood. Women who gained more than 55 pounds were at 41 percent higher risk, according to the researchers.

A much stronger association was found between weight gain and development of breast cancer in postmenopausal women who never used hormones, the researchers said. Women in this group who gained 22 to 44 pounds were at 61 percent higher risk of developing breast cancer; those that gained more than 44 pounds were at almost double the risk of breast cancer than women with minimal weight change.

The authors note: “However, among current and past hormone users, women with greater weight gain did not experience an elevated risk of breast cancer.” The researchers state that a “possible residual effect of postmenopausal hormones on breast tissue” could explain this finding.

The study found that premenopausal and postmenopausal women who were obese or who gained weight in adulthood were more likely to die from breast cancer. This was especially true for postmenopausal women who had never used hormones. These women were more than two times more likely to die from the disease.

The authors conclude: “Thus, avoiding weight gain during adult life may contribute importantly to the prevention of breast cancer incidence and mortality after menopause, particularly among women who do not use postmenopausal hormones.” In an accompanying editorial in the issue of JAMA, Jennifer L. Kelsey, Ph.D., of Stanford University School of Medicine in Stanford, Calif., and John Baron, M.D., of Dartmouth Medical School in Hanover, N.H., state the Huang study contributes to the understanding of the relationship between weight and breast cancer.

They write: “First, the authors find an increased risk for breast cancer in heavy postmenopausal women only among those who have never used hormone replacement therapy; that is, women whose estrogen levels would be low if it were not for their obesity. ... Second, in conjunction with results from some previous case-control and smaller cohort studies, this large cohort study provides perhaps the strongest evidence to date that weight gain from early adulthood is important in the etiology of postmenopausal breast cancer.”

But like many studies that advance knowledge, this study raises several questions that it cannot answer. “A central question is whether weight gain itself brings about physiological changes that effect breast cancer risk, whether the increased risk is simply the consequence of the initial low body weight and the more recent heavy body weight, or whether the relationship is attributable to another variable such as lack of physical activity, which is associated with weight gain and has been linked to breast cancer risk in some studies.” This study is an important illustration of studying separate subgroups of a risk group to determine different susceptibilities.