We found that a higher amount of vigorous physical activity was associated with a small, statistically non-significant decrease in postmenopausal breast cancer risk in our cohort as a whole. However, when we evaluated the relation of vigorous activity to breast cancer among women who were of normal weight, the association became markedly stronger, with risk among women reporting the highest amount of vigorous activity decreasing by about 30% compared with women with no vigorous activity. In contrast, no association between vigorous activity and breast cancer was noted among women who were overweight or obese. In addition, we observed no association between non-vigorous activity and breast cancer, neither in the cohort as a whole or after stratification by BMI. We also found no heterogeneity of the physical activity and breast cancer association according to hormone receptor status.
As published in a recent meta-analysis of the available literature [2
], most previous studies that examined physical activity in relation to postmenopausal breast cancer reported risk reductions of 20% to 80% for the highest compared with the lowest physical activity levels. Some [13
] but not all previous investigations [16
] noted a significant inverse relation with vigorous activity but detected a weaker or no association with non-vigorous activity. That vigorous activity may afford greater apparent protection from breast cancer development than non-vigorous activity is supported by findings that greater intensity of physical activity or level of physical training is related to more pronounced perturbations of sex hormone levels and menstrual function [22
]. However, data from randomised trials among postmenopausal women demonstrate that circulating levels of androstenedione and oestrone, important modulators of breast cancer risk, are lowest among women assigned to engaging in the most amount of overall activity [23
], suggesting that the amount of activity is more relevant than the intensity of activity, at least for reducing oestrogen levels.
We found that the relation of vigorous activity to breast cancer was modified by BMI, with an inverse physical activity association limited to lean or normal weight women. This is consistent with numerous previous studies [16
] observing an apparent protective effect of physical activity on breast cancer risk that was more evident among lean women than overweight women. However, data regarding this issue are equivocal, with some reports noting a more pronounced inverse physical activity and breast cancer relation among overweight women compared with lean women [36
], and other investigations finding no heterogeneity of the association between physical activity and breast cancer according to adiposity level [14
That increased physical activity was related to a more pronounced reduction in risk for breast cancer among lean women compared with overweight women and the observation that the influence of physical activity was almost unaffected by adjustment for BMI suggests an underlying biological mechanism that is independent of body weight control. Possible mechanisms through which physical activity may protect against breast cancer that are independent of BMI include reduced exposure to growth factors, enhanced immune function and decreased chronic inflammation, variables that are related both to greater physical activity and to lower breast cancer risk [47
A non-causal explanation for a stronger inverse relation of vigorous activity among lean women compared with overweight women is that heavier women may not exercise as intensely as lean women. Moreover, non-vigorous activities performed by overweight women, such as light housework, general gardening and light sports, may be misreported as vigorous activities among overweight individuals.
We found very little evidence that the relation of physical activity to breast cancer varied according to hormone receptor subtype, although information on hormone receptor status was available for only a portion of the study subjects. This finding is in line with several previous studies on this topic [14
]. Some investigations did find heterogeneity of the physical activity relation by breast cancer hormone receptor status. For example, in the California Teachers Study [15
] increased levels of both strenuous and moderate recreational activity were related to decreased risks of oestrogen receptor (ER)-negative, but not ER-positive breast cancers. In the Iowa Women's Study [50
] enhanced physical activity level was associated with decreased risks of ER-positive/progesterone receptor (PR)-positive, ER-positive/PR-negative and ER-negative/PR-negative breast cancers. However, the only breast cancers for which a statistically significant inverse relation remained after adjustment for BMI were ER-positive/PR-negative types. A case-control study found a suggestive inverse relation of current recreational activity with ER-negative breast cancers and an apparent increased risk with ER-positive breast cancers [51
]. However, the directionality of those associations was reversed when considering adolescent recreational activity [51
]. Taken together, available data concerning the relation of physical activity to breast cancer according to hormone receptor subtype are currently not sufficiently consistent to draw firm conclusions.
Despite reasonable consistency of our findings with those from the existing literature [2
], a direct comparison of activity levels among women in our study with those from previous investigations is difficult because of substantial variation in the design of physical activity questionnaires across available breast cancer studies. Our questionnaire format may have been associated with some degree of over-reporting of activity as suggested by circumstantial data showing that self-administered activity questions can lead to inflated estimates of the reported time spent engaging in physical activity as compared with interviewer-administered assessments [52
]. However, the main possible correlates of activity over-reporting, including age and body size, were accounted for in our multivariate statistical analyses.
Our physical activity tool included an assessment of physical activity intensity, which appeared to be sufficiently comprehensive to distinguish between vigorous and non-vigorous forms of activity. Nonetheless, we cannot rule out the possibility of misclassification of non-vigorous and vigorous types of activities in our study, which would tend to attenuate relative risk estimates due to random error in capturing and quantifying the most relevant intensity of physical activity. Although our questionnaire was aimed at assessing all types of physical activity, it lacked the level of refinement necessary to evaluate specific individual activities, such as walking.
Women who were more physically active in our cohort tended to have a lower education level than those who were less active. Thus, we cannot entirely rule out the possibility that the inverse association between vigorous activity and breast cancer observed in our study was partly explained by lower socioeconomic status related both to increased activity levels and to decreased risk of breast cancer. On the other hand, lower socioeconomic status among physically active women indicates that a combination of household and occupational activities represented a quantitatively greater contribution to total physical activity among women in our cohort than in other studies in which physical activity assessments were limited to recreational or sports activities, which tend to track positively with elements of a healthy lifestyle and also bear the potential for confounding [51
Our analysis was based on a single, baseline assessment of physical activity, which may not have precisely represented long-term activity habits. Data on physical activity throughout the life course would have been important in examining early-age or long-term physical activity patterns in relation to subsequent breast cancer risk [49
]. Our findings suggest that physical activity in mid to late adulthood is aetiologically relevant for influencing breast cancer risk.
We did not encompass possible alterations in activity levels during follow-up. Conceivably, our single point-in-time measure of physical activity misclassified women with respect to their habitual activity level during the study. In particular, women in our cohort who had recently undergone surgical consultation or therapy for benign breast disease may have subsequently modified their physical activity habits. Because our physical activity questionnaire was designed to assess recent exposure to physical activity, any impact of breast cancer screening on activity levels during the subsequent period of follow-up would have diminished the ability of our instrument to reflect true long-term physical activity levels. However, because our physical activity assessment preceded the diagnosis of breast cancer, potential misclassification of physical activity would have tended to be non-differential with respect to disease status, which would have resulted in an attenuation of the true association. In addition, findings from other prospective cohorts [53
] indicate that physical activity levels tend to track well over time, which helps explain why investigations employing a single baseline measure have uncovered relevant associations between physical activity and breast cancer using that strategy.
We also were not able to encompass changes in potential confounding variables or effect modifiers during follow-up. Large changes in levels of variables such as BMI or menopausal hormone therapy use could have influenced our findings.
Notable strengths of our study include its large sample size, prospective design, high follow-up rate, and availability of relevant known or suspected breast cancer risk factors. These features enabled us to minimise major bias and confounding. Consistent with the majority of previous investigations of physical activity and breast cancer [2
], few variables confounded our findings.
An important limitation of our study is our reliance on self-reported physical activity, a method that is prone to both systematic and random errors. A further potential limitation is that our cohort comprised predominantly Caucasian women who volunteered to participate in a long-term follow-up study. Thus, our findings may not be strictly relevant to all women. In addition, women who had undergone a previous breast biopsy were over-sampled in our study, potentially further decreasing the general nature of our results. However, the relation of physical activity to breast cancer was not modified by breast cancer screening history in our study, suggesting broad applicability of our results.