Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened latency and/or increased mammary tumor (MT) incidence in animals. Elevated body weight is usually associated with hormone-responsive tumors. In agreement with these data we previously showed that latency of hormone-responsive MTs in MMTV-TGF-α mice with diet-induced obesity was significantly shortened. Here, we used the same protocol to determine the impact of diet-induced obesity on estrogen receptor-negative MT development in MMTV-neu (strain 202) mice. Mice were fed a low-fat diet (n = 20) or a high-fat diet (n = 54) from 10 wk of age. Body weight at 19 wk of age was used to assign high-fat mice to obesity-prone, overweight, and obesity-resistant groups. Mice were euthanized due to MT size or at 85 wk of age. Final body weights of obesity-prone mice were heaviest, and those of obesity-resistant and low-fat groups were similar. Fat pad weights were heaviest in obesity-prone mice followed by overweight and obesity-resistant groups, and lightest in low-fat mice. Serum IGF-1 levels were similar for low-fat and high-fat mice, whereas leptin was higher in high-fat mice (P < 0.0001). MT latency, incidence, metastasis, and burden were similar for all groups. These findings support that obesity is not a risk factor for development of estrogen-negative breast cancer.
Bibliographical noteFunding Information:
This work was supported in part by the Hormel Foundation and grants DAMD17–97–7055 (MPC), CA79808 (NJM), and DK16105 (JPG). Its contents are solely the responsibility of the authors. We are indebted to Dr. Sandra Gendler for providing male MMTV-neu mice to establish our colony. Michelle Jacobson, Tina Jacobson, Jessie Freitag, and Sue Getzin provided excellent care of the mice. We thank Karan Crilly for performing the leptin and IGF-I assays. In addition, we owe a special debt of gratitude to Drs. Peter Mattjus and Pia Roos-Mattjus for transporting samples from Austin to Rochester. The University of Minnesota is an equal opportunity educator and employer. N. J. Maihle is currently affiliated with the Department of OB/GYN and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520. Address correspondence to M. P. Cleary, Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912. Phone: 507–437–9655. FAX: 507–437–9606. E-mail: mpcleary@ hi.umn.edu.