Obesity and weight gain associated with poorer breast cancer survival

Women who are overweight prior to breast cancer diagnosis, or who are lean but gain weight following diagnosis, are more likely to have their disease return or die of the disease, a new study shows. This effect was found to be particularly pronounced among women who had never smoked. The study is to be published online January 31 in the Journal of Clinical Oncology (JCO).

To evaluate the relationship between weight gain and breast cancer survival, researchers examined detailed lifestyle and medical history information of 5,204 breast cancer patients over 24 years. The women were participants of the Nurses' Health Study (NHS), a prospective study of the health of 121,700 female nurses conducted between 1976 and 2000. Researchers used body mass index (BMI) - the ratio of a person's height in meters to their weight in kilograms - to classify women as normal weight (BMI of 18.5 to 24.9), overweight (BMI of 25 to 29.9), or obese (a BMI above 30). Researchers also computed change in weight before and after diagnosis and classified women as losing weight, maintaining weight, gaining a modest amount of weight, and gaining a substantial amount of weight.

Although other studies have addressed the link between obesity and breast cancer survival, no prior studies had separated smokers from non-smokers. Researchers suggest that the failure to separate these groups in analyses may have obscured the influence of weight or weight gain on breast cancer recurrence and mortality.

Researchers found that high weight prior to diagnosis was associated with poorer survival, but found this was particularly evident in women who had never smoked. Never smokers who were overweight (BMI of 25 kg/m2 or higher) at diagnosis were nearly twice as likely to die as never smokers who were normal-weight (BMI less than 25 kg/m2).

Furthermore, weight gain after breast cancer diagnosis was also associated with an increased risk of recurrence and death, and this risk increased as weight gain increased. This was also most evident in women who had never smoked. Never-smoking women who gained more than 2.0 kg/m2 or an average of 17 lbs, were 1.5 times more likely to have a recurrence of their disease or to die during follow-up than women who maintained their weight (within 0.5 kg/m2 of their original weight).

"Combining smokers and non-smokers in analyses may mask the true relationship between weight and survival after a breast cancer diagnosis, since smoking is generally related to both lower levels of weight and a higher risk of death overall," said Candyce Kroenke, ScD, of the Department of Medicine at Brigham & Women's Hospital, Harvard Medical School, and lead author of the study.

"Researchers have also speculated that obesity acts on cancer by raising the body's levels of sex hormones such as estrogen, particularly in post-menopausal women. However, since smoking may promote the formation of less biologically active estrogens, it may be more difficult to understand the relationship between weight and breast cancer when combining smokers and non-smokers in a study. This study suggests a more complex relationship between weight and breast cancer survival than was originally considered," Dr. Kroenke added.

The researchers noted that the associations between weight gain and survival were stronger in women with early stage cancer, those who were normal-weight prior to diagnosis, and those who were premenopausal compared with women with later stage cancer, or those who were overweight or postmenopausal.

"Women recently diagnosed with breast cancer or at high risk for the disease should take steps to maintain a healthy weight to reduce the risk of recurrence and death," said Dr. Kroenke.

An accompanying editorial by Rowan T. Chlebowski, MD, PhD, Medical Oncologist, at Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center noted that the study raises important questions about the interactions between smoking history, obesity, and breast cancer survival.

"This study underscores the need for more clinical data to determine which lifestyle interventions can most effectively help women achieve or maintain a healthy weight following diagnosis with breast cancer," said Dr. Chlebowski.

"Weight, weight gain and survival after breast cancer diagnosis." Candyce Kroenke, et al, Channing Laboratory, Department of Medicine, Brigham & Women's Hospital, and Harvard Medical School, Boston, MA.

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