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Is Leptin a Mediator of Adverse Prognostic Effects of Obesity in Breast Cancer?

From the Department of Medicine, Department of Surgery, Division of Clinical Epidemiology at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto-Sunnybrook Regional Cancer Centre, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada

Address reprint requests to Pamela J. Goodwin, MD, Mount Sinai Hospital, 1284-600 University Avenue, Toronto, Ontario, Canada M5G 1X4; e-mail: pgoodwin{at}mtsinai.on.ca

PURPOSE: Leptin, an adipocyte-derived cytokine that is elevated in obesity, has been associated with carcinogenesis, tumor migration and invasion, enhancement of angiogenesis, and increased aromatase activity. It has been suggested that leptin may mediate adverse prognostic effects of obesity in breast cancer.

PATIENTS AND METHODS: Four hundred seventy-one women with surgically resected T1-3, N0-1, M0 breast cancer were studied. Leptin was assayed in stored fasting blood specimens obtained before adjuvant therapy. Women were followed prospectively for distant disease-free survival (DDFS) and overall survival (OS).

RESULTS: Patients ranged from 26 to 74 years of age, and staging was as follows: T1 = 262, T2 = 151, T3 = 23, TX = 35, N0 = 323, and N1 = 148. Estrogen receptor was positive in 286 patients, and progesterone receptor was positive in 259 patients. One hundred forty-five patients received adjuvant chemotherapy, 146 received adjuvant tamoxifen, 46 received both, and 134 received neither. Mean leptin was 15.2 ± 10.1 ng/mL. Univariately, leptin was associated with OS (overall P = .049; P = .014 postmenopausal). Leptin was not associated with DDFS overall or in any menopausal subgroup (P .19). In multivariate Cox modeling, leptin was not significantly associated with DDFS or OS (P = .11 and 0.075, respectively). Adjustment for insulin or body mass index further reduced the association of leptin with outcome.

CONCLUSION: Although leptin is strongly correlated with obesity and insulin, we could not show that it is independently associated with prognosis in early-stage breast cancer. Because we cannot rule out modest prognostic effects, we recommend additional research to explore this potential association, particularly in postmenopausal women.

Funded by the Canadian Breast Cancer Research Alliance and the Medical Research Council of Canada (currently the Canadian Institutes of Health Research).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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