Physical Activity and Breast Cancer: Is There a Link?
Authors: J. F. Dorgan
Journal: JNCI Journal of the National Cancer Institute (1998)

Physical activity has diverse physiologic effects through which it could potentially alter breast cancer risk. Currently, the most prominent hypothesis is that physical activity may lower risk through hormonal mechanisms. Estrogens are mitogenic to breast epithelial cells and are believed to play a key role in breast cancer promotion and possibly initiation (1). Older age at menarche, younger age at menopause, and perhaps a higher frequency of long and irregular menstrual cycles lower breast cancer risk (2). Compared with their more sedentary peers, highly trained athletes and dancers (3), and possibly recreational athletes (4,5), have delayed menarche and an increased frequency of long or irregular menstrual cycles. Although obesity is inversely related to the risk of premenopausal breast cancer, after menopause occurs, estrogens are synthesized from androgens in adipose tissue and obesity is directly related to risk (6). Physically active women of all ages are leaner than their more sedentary counterparts (7), but leanness is a major determinant of serum estrogen concentrations only for postmenopausal women (8). Because of its biological plausibility and consistency, the hypothesis that physical activity lowers breast cancer risk through hormonal mechanisms is intuitively appealing. In this issue of the Journal, Rockhill et al. (9) present findings from the Nurses’ Health Study II on the relationship between nonoccupational physical activity and breast cancer risk in women up to 48 years of age at diagnosis. The analysis was based on 104 468 female nurses followed for 6 years, during which time 372 invasive breast cancers were diagnosed. Nurses who frequently participated in strenuous activities during late adolescence had essentially the same risk of developing breast cancer as those nurses who never participated in such activities (relative risk [RR] 4 1.1; 95% confidence interval [CI] 4 0.8– 1.6). Similarly, nurses who spent the most time engaged in moderate and strenuous nonoccupational activities at 25–42 years of age had the same risk of breast cancer as those who spent the least time in these activities (RR 4 1.1; 95% CI 4 0.8–1.5). Results were unchanged when adjusted for potential confounders or stratified on possible effect modifiers. The lack of even a suggestion of a protective effect of nonoccupational physical activity for breast cancer in young women from the Nurses’ Health Study II is disappointing, but not surprising. Although Bernstein et al. (10) reported a significant 60% lower risk of breast cancer at a young age for women who regularly participated in recreational activities, a recent study by Gammon et al. (11) did not detect an association. Conflicting results also emerge from studies [reviewed in (12)] of postmenopausal women and of occupational activity. Inverse associations of physical activity with breast cancer are reported more often than null or positive associations, but frequently risk estimates are small and statistically nonsignificant, a dose–response relationship is not seen, or the association is limited to a subgroup of participants. Physical activity is one of numerous determinants of age at menarche and menstrual function, and other factors may be more important for most women. Associations of recreational sports activity with age at the onset of menses are inconsistent (4,13). In addition, in a study of college women (14), moderate physical activity had only a minimal association with cycle length, as estimated from menstrual diaries. Physical activity contributes to energy balance, but other factors including genetics also affect body weight (7). Age at menarche and, for postmenopausal women, obesity are established but not particularly strong risk factors for breast cancer; the association with menstrual cycle characteristics is less well established (2). Participants in the Nurses’ Health Study II (15) who were older at menarche had a 34% reduction in the risk of premenopausal breast cancer. Those who had longer or irregular cycles had a 20%–60% reduction in risk. This cohort is still young, and few members are postmenopausal. In another large cohort (16), the most obese postmenopausal women had a 50% elevation in the risk of breast cancer. Therefore, even if physical activity prevents breast cancer by contributing to a delay or disruption in menstrual function in young women and the maintenance of ideal body weight in older women, within the range typical of women in the United States, the effect of physical activity on risk, if one exists, is likely to be modest. Assessment of physical activity in epidemiologic studies is extremely difficult. Typically, questionnaires with varying degrees of specificity are used. Although most are not validated, the questionnaire used in the Nurses’ Health Study II was evaluated against multiple, 7-day activity diaries (17). The correlation between the two instruments’ measures of physical activity was .62, which compares favorably with other activity questionnaires (18,19). Findings on reproducibility were similar. Although questionnaires may yield reasonably valid and reliable estimates of physical activity, they misclassify some individuals, which will attenuate and could obscure weak associations of physical activity with breast cancer. Age at onset of menses and frequencies of menstrual disturbances in elite and possibly in recreational athletes differ by sport, intensity and duration of exer-