We observed that >7 hour per week of recent (in the past 10 years) but not historical (from ages 15-18, 19-29, or 35-39 years) moderate-to-vigorous intensity physical activity was associated with a 16% reduced risk of postmenopausal breast cancer. No relation between breast cancer risk and light intensity physical activity during any of the periods of life examined was observed. Associations did not appear to vary by ER status, breast tumor stage, or tumor histological subtype.
The inverse association observed in our study (RR:0.84, 95%CI:0.76,0.93) is similar to the 13% reduction in postmenopausal breast cancer risk (RR:0.87, 95%CI:0.81,0.95) observed for women reporting ≥ 5 episodes per week of physical activity during the year preceding assessment in the baseline NIH-AARP cohort [24
]. Although both of these risk estimates are less pronounced than the 20-40% risk reductions reported in reviews of the physical activity-breast cancer relationship [3
], directly comparing risk estimates across studies is difficult considering variation in the instruments used to measure physical activity, inconsistencies in the parameters of physical activity that are assessed, and underlying differences in the study populations.
Only two previous studies [7
] reported on both the intensity level and time of life of physical activity in relation to breast cancer risk. A Polish case-control study [14
] evaluated the association of physical activity of various intensities from light to vigorous across decades of life (age 20-24, 25-29, 30-34, 35-39, 40-49, 50-59, 60-69 years). Significant inverse associations were observed for physical activity across multiple decades of life with risk of breast cancer. Inverse associations were generally stronger for moderate-to-vigorous recreational activity than for total recreational activity, and a high level of moderate-to-vigorous recreational activity during ages 50-59 years was associated with the largest reduction in breast cancer risk.
In the second study to look at the combination of intensity and time in life of physical activity [7
], the California Teachers' Study (CTS) investigated moderate and strenuous intensity physical activity from ages 18-24, 25-34, 35-44, 45-54 years and in the 3 years preceding baseline assessment. Contrasting the Polish case-control study [14
] and our results, the CTS [7
] observed no association of moderate or strenuous physical activity during the three years preceding baseline with breast cancer risk. Yet a high versus low level of strenuous physical activity from age 18 years through the three years preceding baseline was associated with a 20% reduced risk of breast cancer (RR:0.80, 95%CI:0.69-0.94), and moderate physical activity from age 18 years through the three years preceding baseline showed a statistically non-significant 6% reduced breast cancer risk (RR:0.94, 95%CI:0.81-1.08) [7
]. As the relation of physical activity with breast cancer risk appears to vary by menopausal status [5
], inconsistent results may be due to differences in the study populations; whereas our study included only postmenopausal women, and the Polish case-control study was comprised of 70.5% postmenopausal women, only 51.4% of women in the CTS were postmenopausal.
Our observation that recent physical activity showed a stronger inverse association with breast cancer risk than historical activity is supported by two systematic reviews [3
] and three prospective studies among postmenopausal women [12
]. Furthermore, our finding that moderate-to-vigorous but not light physical activity was inversely related to breast cancer risk is supported by some [9
], but not all [10
], studies on the topic. Many previous reports of the relation of physical activity intensity with breast cancer risk have compared moderate with vigorous physical activity; numerous studies [5
] have shown stronger associations for vigorous intensity activity, but other studies have not found a dose-response according to physical activity intensity [10
]. The physical activity questionnaire in our study combined moderate and vigorous intensity categories, which is consistent with the intensity level cited in the current public health recommendations [31
]. However, we could not evaluate heterogeneity in the association of moderate versus vigorous activity with breast cancer risk within our study in order to compare with prior studies or to determine whether moderate activity is sufficient for reducing postmenopausal breast cancer risk.
The observed protective effect of moderate-to-vigorous physical activity in our study is biologically plausible, as there is some evidence that a high intensity of physical activity is associated with a reduction in estradiol [33
] and enhanced sensitivity to insulin [34
]. Whereas recent studies suggest that in postmenopausal women the effect of physical activity on estrogens may be mediated by loss of body fat [35
], the lack of confounding by or interaction with BMI in our study supports an independent influence of physical activity. Physical activity also appears to modulate immunity in a manner in which moderate activity is beneficial to the immune response, but sedentary behavior and highly strenuous activity can impair immune function [37
We observed very little heterogeneity in the relation of physical activity to breast cancer tumor characteristics, regardless of the intensity or time of life of physical activity. A lack of heterogeneity in the relationship of physical activity with ER-defined breast cancer is consistent with the Breast Cancer Detection Demonstration Project cohort study [6
] and five case-control studies [14
]. However, other studies have reported stronger inverse associations of physical activity with ER-positive tumors [14
] or ER-negative tumors [5
]. A suggested inverse relation of recent moderate-to-vigorous activity with ER-negative tumors was observed in both the current study and the baseline NIH-AARP cohort [24
]. Yet the substantially smaller number of ER-negative breast cancer cases in the present study likely limited our ability to detect heterogeneity by ER-status.
In addition, we observed similar associations for recent moderate-to-vigorous physical activity with invasive and in situ
breast cancer. This finding is consistent with three cohort studies [7
] and four case-control studies [14
], but diverges somewhat from the Cancer Prevention Study II (CPSII) [20
] and a German case-control study [41
] in which no association was apparent between recent recreational physical activity and in situ
breast cancer. However, each of these studies [20
] included only 205 in situ
tumors and thus may have lacked power to detect an association.
Observation of similar associations of moderate-to-vigorous activity during the past 10 years with ductal and lobular histological subtypes in our study corresponds to results from a Polish case-control study [14
]. These results suggest that moderate-to-vigorous intensity physical activity influences postmenopausal breast cancer risk through estrogenic and non-estrogenic pathways, in both early and more advanced tumors, and affects tumors of a variety of histological subtypes.
Strengths of our study include the large sample size, the prospective design, and the information on timing and intensity of physical activity. In addition, with the availability of detailed questionnaire data regarding breast cancer risk factors, we could control for potential confounding variables. While our physical activity questionnaire was not directly validated, the inverse associations we observed between recent physical activity and BMI and recent physical activity and current cigarette smoking suggest construct validity of our instrument. Furthermore, our physical activity categories classified 49% of women in our study as achieving the current public health recommendation of at least 2.5 hours per week of moderate-to-vigorous physical activity to maintain health [31
], comparable to the 47.5% of U.S. women estimated to achieve this level of activity in a 2007 national survey [45
]. One limitation of our study, however, is that the generalizability of our results may be limited due to the relatively low response proportion to our initial postal questionnaire.
In our cohort of postmenopausal women, we were able to examine the relation of physical activity intensity across the lifespan to postmenopausal breast cancer risk, but we relied upon recall of physical activity during time periods in the distant past. Prior studies have shown reasonably strong correlations between physical activity recalled from 3-5 years [46
] and 15 years [47
] in the past with physical activity measured objectively at that time, although the validity of physical activity over longer periods of recall is not known. Our observation that physical activity was positively correlated across proximate age periods suggests that our ability to discriminate between certain age periods may have been limited. Furthermore, it is likely that the null associations with historical physical activity in our study resulted from a greater degree of misclassification of historical than recent physical activity.
Additionally, if participants exhibit better recall of vigorous intensity activities than those of lower intensity [48
], the observation of an association of moderate-to-vigorous physical activity and the lack of an association of light physical activity with breast cancer risk might be explained not by etiological differences, but by misclassification. Yet in our prospectively designed study, exposure measurement error is likely to be non-differential by case status, whereas misclassification of physical activity level in case-control studies has been shown to distort risk estimates as a result of recall bias [51
]. It is possible that we did not observe an association of light intensity physical activity at any time period of life with breast cancer risk due to the examples of light activities given in the questionnaire. Our examples of light intensity activities may have reflected a combination of sedentary behaviors (eg: golf [riding in a cart], fishing) and truly light activities (eg: bowling, table tennis, slow walking/slow dancing, light calisthenics, light gardening, horseshoes/croquet, light housework), thereby preventing the assessment of a true association between breast cancer risk and light physical activity [52
]. In addition, while providing categories of physical activity duration (<1, 1-3, 4-7, or >7 hours per week) eases the recall burden of participants, such categorization may also permit misclassification if differences in risk exist for more subtle distinctions in the amount of time spent active.