Obesity at diagnosis confers worse outcome in patients with early stage breast cancer treated with breast conservation therapy

Abstract

Obesity has been shown to be a risk factor for the development of primary breast cancer. Prior studies have reported contradictory results regarding the influence of obesity on outcome in breast cancer patients. Therefore, the prognostic influence of obesity remains uncertain, especially in early stage breast cancer patients. This study analyses the impact of obesity on outcome in women with early stage I/II breast cancer treated with conservative surgery and radiation therapy. From 1978 to 2003, 2010 women with Stage I/II breast cancer underwent lumpectomy, axillary dissection and radiation therapy with or without systemic therapy. The median age was 58 years (range 20–89). Obesity was defined by using the Quetelet’s Index (also called the body mass index or BMI), which is the patient’s weight divided by the height squared. Patients were categorized into three groups according to their Quetelet’s Index (QI), which was calculated at the time of diagnosis. The groups were defined as the normal weight group (QI range >0 ≤ 3.2), the overweight group (QI range >3.2 ≤ 4), and the obese group (QI range >4). 701 patients (35%) were considered obese, 857 patients (43%) were overweight, and 452 patients (22%) were in the normal weight group. The median follow-up was 61 months. The three groups were compared for differences in the clinical factors of age, race, tumor size, family history, menopausal status; the pathologic factors of histology, extensive intraductal component (EIC), lymphovascular invasion (LVI), final margin status, nodal status, receptor status; and treatment-related factors of regions treated with radiation therapy and systemic therapy. Cox multivariate regression models were used to determine the independent predictors of local failure (LF), distant metastases (DM), cause-specific survival (CSS), and overall survival (OS). Five-year rates were estimated using Kaplan-Meier methodology and comparisons were made using the log-rank test. Statistically significant differences between the three weight groups were observed for age (p < 0.0001) and menopausal status (p < 0.0001), with the obese weight group being comprised of older and more post-menopausal women. There was no statistically significant difference observed for tumor size or number of involved lymph nodes between the three weight groups. The actuarial five-year rates of DM were 7%, 6% and 10% for the normal weight, overweight and obese weight groups, respectively (p = 0.06). The actuarial five-year rates of CSS were 96%, 95% and 93% for the normal weight, overweight and obese groups, respectively (p = 0.05). The actuarial five-year rates of OS were 92%, 92% and 88% for the normal weight, overweight and obese groups, respectively (p = 0.0035). Using a Cox multivariate proportional hazards regression model, obesity was found to be a statistically significant independent predictor of increased distant metastases (p = 0.0145), and worse cause-specific survival (p = 0.0060). Obesity was not found to be a significant predictor of local failure. Obesity at the time of diagnosis of early stage breast cancer is a significant predictor for poorer outcome. Women who are obese are at greater risk for breast cancer death and distant metastases, although they do not present with more advanced stage disease compared with normal weight patients. We have demonstrated a significant association between obesity and adverse breast cancer outcome in patients with early stage breast cancer. Because the prevalence of obesity increases with age, as does the risk for breast cancer, interventions that enhance weight control may have a substantial effect on breast cancer outcome