EIGHT WEEKS OF EXERCISE TRAINING DOES NOT ALTER MAMMARY TUMOR PHENOTYPE IN ADOLESCENT RATS

Abstract

Physical activity has been linked to reduced breast cancer incidence in both epidemiologic studies and animal models. The purpose of this study was to determine whether mammary tumors that develop in response to a chemical carcinogen differ in rats that were exercise trained. Identifying tumor type and characteristics may lead to understanding the mechanism by which exercise inhibits cancer development. Ninety female SD rats were randomized to baseline (n = 10), exercise (EX; n = 40), or sham-exercise (SHAM; n = 40). 1-methyl-nitrosourea (MNU) was injected (50 mg/kg bw) at 21 days of age (doa) and training started at 28 doa. Exercise consisted of treadmill running (20–25 m/min, 15% grade, 30 min/d, 5 d/wk). Sham rats were placed on a stationary treadmill (15% grade, 30 min/d, 5 d/wk). Animals were weighed and palpated for tumors 2x/wk. Ten animals at baseline (28 doa) and groups of 10 EX and 10 SHAM were sacrified every 2 wks for 8 wks to evaluate tumor and mammary gland development. Tumors were excised at necropsy, weighed, and fixed in 10% formalin for histopathological analysis. 5 μm H&E stained sections were classified according to the International Harmonization of Rat Nomenclature independently by 2 pathologists blinded to group assignment. At 8 wks, tumor incidence was 100% in all groups; mean (± SD) number of tumors per rats was 5.4 ± 2.6 with no difference between EX and SHAM rats. Growth rates of individual tumors were significantly reduced in EX rats. Ninety-eight percent of all tumors identified at the 8 wk necropsy were adenocarcinomas. No phenotypic difference in tumor type was noted between groups. Tumors exhibited varying degrees of inflammation (0–3 scale). While the degree of inflammation correlated with tumor size (r = .60), it did not differ between EX and SHAM rats (mean score EX-1.93; SHAM-1.86). The data suggest that 8 wks of moderate exercise training does not alter the phenotype of MNU-induced mammary tumors. They also suggest that alterations in other cancer endpoints (incidence, multiplicity, growth rate) observed previously and in the current study are not a function of tumor type. Supported by NIH (KO7 CA79554)