Recreational physical activity and risk of postmenopausal breast cancer based on hormone receptor status

Background: Physical activity is a potentially modifiable breast cancer risk factor. There is considerable recent evidence to suggest that risk factors for breast cancer differ based on its subtype, particularly estrogen receptor (ER)/progesterone receptor (PR) status, but this has been less well studied for physical activity. The objective of this study was to examine the association of physical activity with breast cancer incidence based on ER/PR status of the tumor. Methods: The Iowa Women's Health Study is a prospective cohort study of 41 836 postmenopausal women. Recreational physical activity was self-reported on the baseline questionnaire, and 3 levels (high, medium, and low) were defined. Breast cancer incidence and ER/PR status, through 18 years of follow-up, were ascertained by linkage with the Iowa Surveillance, Epidemiology, and End Results Cancer Registry. Cox proportional hazards models were used to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs) of breast cancer, adjusting for other breast cancer risk factors. Results: During 554 819 person-years of follow-up, 2548 incident cases of breast cancer were observed. Compared with low physical activity, high physical activity levels were inversely associated with risk of breast cancer (RR, 0.86; 95% CI, 0.78-0.96), and there were inverse associations for ER-positive (ER⁺)/PR-positive (RR, 0.87; 95% CI, 0.75-1.00), ER⁺/PR-negative (PR^-) (RR, 0.67; 95% CI, 0.47-0.96), and ER-negative/PR^- (RR, 0.80; 95% CI, 0.56-1.14) tumors. Further adjustment for body mass index attenuated the overall association with breast cancer (RR, 0.91; 95% CI, 0.82-1.01) and for ER ⁺/PR-positive tumors (RR, 0.94; 95% CI, 0.81-1.08), while there was no change for ER⁺/PR^- tumors (RR, 0.66; 95% CI, 0.46-0.94). Conclusions: Higher recreational physical activity might reduce the risk of postmenopausal breast cancer overall. Risk reduction varies by ER/PR status of the tumor, being most marked for ER⁺/PR^- tumors, which, in general, have been associated with a clinically more aggressive tumor phenotype. If confirmed in additional studies, these results would suggest that additional mechanisms, besides an effect on body mass, may account for observed protective effects of physical activity in reducing breast cancer.