Abstract PR-4: Physical activity and postmenopausal breast cancer: Effect modifications by hormone receptor status and breast cancer risk factors

Physical activity (PA) has been inversely associated with postmenopausal breast cancer risk. Most studies regarded breast cancer as a single disease, at best separated by menopausal status. Yet, breast cancers are heterogeneous and likely to have different etiologies. Furthermore, little is known about the biological mechanisms by which physical activity reduces breast cancer risk and about potential modifying effects of other risk factors. Information on the association of PA with breast cancer according to hormone receptor and risk factor status may provide insight into mechanisms of action.

We analyzed these associations in 3,414 postmenopausal cases and 6,569 controls from a population-based case-control study on breast cancer conducted 2002-2005 in two regions in Germany (MARIE study). Comprehensive data on risk factors were collected. PA in the age periods 30-49 and 50+ years was assessed, including leisure-time PA (sports, cycling, walking) and non-recreational PA (occupational and household activities). Polytomous logistic regression was used to model the association between the PA variables and breast cancer according to estrogen- and progesterone- receptor-status (ER/PR). Case-case comparisons were performed to evaluate heterogeneity between cancer subgroups (P_diff). Effect modifications by other cancer risk factors were evaluated by including an interaction term with leisure-time PA as continuous variable into unconditional logistic regression models, separately for each ER/PR type.

The effect of leisure-time PA since age 50 on ER+/PR+ differed significantly from the effects on ER+/PR- (P_diff = 0.028), ER-/PR+ (P_diff = 0.024), and ER-/PR- (P_diff = 0.028), with more active women having reduced risk for ER+/PR+ carcinomas compared to less active women (OR = 0.71, 95% CI = (0.60 - 0.85) for the highest vs. lowest quintile; linear trend P = 0.0001), but no effects for the other receptor-types. Effects of PA during age 30-49 years were similar but less pronounced.

The association between leisure-time PA and ER+/PR+ carcinoma risk was significantly modified by breastfeeding (p_interaction = 0.045) with a protective effect for women who ever breastfed (OR = 0.62 (0.50 - 0.77) highest vs. lowest PA 50+ quintile), while no risk reduction was observed for women who never breastfed, irrespectively whether they were parous or nulli-parous (OR= 0.95 (0.72 - 1.25)). Effect modification was also observed for benign breast diseases, but statistically significant only for PA during 30-49 years (p_interaction = 0.023). For women who ever had a benign breast disease a clear protective effect was observed (OR = 0.68 (0.52 - 0.89) for PA 30-49; OR = 0.56 (0.42 - 0.74) for PA 50+), but there was no effect for women without benign breast diseases. No effect modification was found for family history of breast cancer, BMI, and parity.

These findings suggest that leisure-time PA may reduce postmenopausal breast cancer risk at least in part via hormonal pathways. The protective effects of PA appear to be more pronounced for women who had ever breastfed or ever had a benign breast disease. However, these observed effect modifications need further confirmation.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-4.