Obesity and Early-Stage Breast Cancer

The observation of Kroenke et al that weight and weight gain are associated with increased breast cancer recurrence and mortality, especially in never-smoking women, builds on a substantial body of evidence in this area and provides new information about obesity and breast cancer. Although tobacco use has not been linked historically to breast cancer, smoking has recently been associated with an increased risk of breast cancer development. In women with breast cancer, current smoking has also been linked with increased lung recurrence risk, as well. Taken together, these observations raise an intriguing hypothesis regarding interaction among smoking history, obesity, and the risk of breast cancer recurrence. The authors acknowledge that there are study limitations, including reliance on self-reported weight, a nonvalidated recurrence methodology, and a lack of information on adjuvant therapy. Body mass index (BMI) changes were calculated from a given height and the patient’s selfreported weight, for which validity information is provided. However, issues related to reliable weight reporting during a period of weight change may differ from those in women with stable weight. A greater question is raised by the breast cancer recurrence methodology. Recurrence was determined using an innovative approach, which assumed that any new cancer in the lung, liver, bone, or brain represented breast cancer recurrence. Given that, for example, a smoker with a so-called lung cancer could potentially be misclassified, perhaps the study end point could be more accurately characterized as disease-free survival. Additional validation efforts to clarify this issue would be useful. Some of the identified design concerns, such as limited information on cancer therapy, have been addressed by retrospective analyses of data from randomized adjuvant therapy trials. In such studies, breast cancer stage is well characterized, comorbid condition influence is minimized by entry criteria, systemic treatment is defined bt the protocol, and recurrence is well characterized. The International Breast Cancer Study Group reported a cumulative experience involving 6,792 patients from randomized trials evaluating chemotherapy and endocrine therapy over a 15year period. In this large population, patients with a normal BMI had significantly longer overall survival and disease-free survival than patients with intermediate or obese BMI. When adjusted for other factors, BMI significantly influenced overall survival (P .03) but not diseasefree survival (P .12), with a greater effect seen in preand perimenopausal women. Dignam et al, analyzing results from a randomized trial evaluating tamoxifen in more than 3,500 women with negative lymph nodes and estrogen receptor–positive tumors, showed comparable findings. Although obesity had no significant effect on recurrence risk or tamoxifen efficacy, overall mortality was significantly greater for obese breast cancer patients compared with those of normal weight. Improved survival and quality of life are primary objectives of therapies provided to women with early-stage breast cancer. The observed influence of obesity on nonbreast cancer–related survival will likely be of increasing importance in determining outcome of breast cancer patients in the future, given that breast cancers are now diagnosed at an earlier stage when other medical conditions represent substantial competing mortality risks. For example, in the Women’s Health Initiative hormone trials, when postmenopausal women between the ages of 50 to 79 years had yearly mammography as a protocol requirement, breast cancers were diagnosed at an average size of 1.5 cm, and only 15% were lymph node-positive. In addition, mammographically detected tumors have a more favorable prognosis than tumors of similar size found outside of screening. Thus, attention to the morbidity and mortality consequences of obesity will likely play an increasing role in determining breast cancer patient outcome. Obese women are more likely to have lower physical activity and higher caloric and fat intakes when compared with nonobese women, with all three factors—at least in some reports—associated with increased breast cancer recurrence risk. Obesity is associated with higher grade breast cancers, especially in black women. In addition, JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 7 MARCH 1 2005