There is a quickly growing body of epidemiologic data on the association between exercise and breast cancer, which was recently reviewed in depth by Thune and Furberg .
Over 20 published cohort studies [6–26] have investigated the association between physical activity and risk of breast cancer, the majority of which showed clear evidence of a lower risk for breast cancer in women who were classified at the highest levels of physical activity [7, 9, 10, 12, 13, 16, 18, 20, 21, 23–27].
The reduction in risk ranged from 10%-70% for the most active women and, on average, was 30%-40% lower for women who exercised for 3–4 hours per week at moderate to vigorous levels. The definition of "most active" varied greatly by study and depended on the questions asked, the population studied, and the researchers’ choice of categories for amounts of activity.
In a study of over 25,000 Norwegian women, trends toward lower risks for breast cancer with greater levels of leisure time physical activity (trend p = 0.08) and physical activity at work (trend p = 0.004) were observed .
There have been two reports from the Nurses’ Health Study cohorts: one looked at recreational activity reported at just one point in time  and one looked at repeated measures of activity at several time points during follow-up .
While the former found no association between physical activity and risk for breast cancer, the latter found that women who engaged in an average of 7 or more hours per week of physical activity had an 18% lower chance (95% confidence interval [CI] = 3%-30%) of developing breast cancer than women who engaged in less than 1 hour per week of such activities.
Activity other than leisure was not assessed, and there may be a considerable effect of occupational activity in a population of nurses.
Some cohort studies compared women according to participation in college sports, some looked at occupational physical activity only, several examined recreational exercise only, and others studied both occupational and recreational physical activity.
Methods of assessment of physical activity were unique to each study, ranging from simply asking subjects questions such as, "In your usual day, aside from recreation, how active are you?," to a physician-administered questionnaire that ascertained how many hours per day the participant usually spent sleeping, resting, sedentary, or at slight, moderate, or heavy activities, to detailed questions involving the participants’ historical and current levels of regular participation in various sports and other recreational exercise activities at different life periods.
More than two dozen case-control studies have been published on the association between physical activity and risk of breast cancer , more than three-quarters of which support a lower risk for breast cancer in women who were the most active compared with sedentary women. Reduction in risk ranged from 10%-70%.
Lower risks associated with greater physical activity have been observed for both premenopausal and postmenopausal breast cancer. Most studies have been conducted in non-Hispanic white women, although data from some studies suggest that physical activity is associated with a lower risk for breast cancer in women of diverse races and ethnicities [26, 28–31].
It is not clear at what ages physical activity provides the most protection against breast cancer. In a small number of case-control studies [32–34], lifetime leisure activity was ascertained, while in other studies, activity levels at adolescence and discrete adult periods were obtained. Some studies found a lower risk with greater activity in adolescence, while in other studies, risk reduction was limited to adult activities. D’Avanzo et al. found similar effects of occupational physical activity occurring at ages 15–19, 30–39, and 50–59 on risk of breast cancer, but found a stronger negative association between recreational exercise and risk at ages 30–39 and 50–59 than at ages 15–19 .
Levi et al. found that greater occupational activity at any time between adolescence and the sixth decade of life was associated with a lower risk . McTiernan et al. found a lower risk associated with adult activity and no effect of activity in adolescence .
Friedenreich et al. found that, while greater lifetime activity gave the most benefit, exercise in postmenopausal years was protective . Most studies, however, looked at activity at just one time point, usually either right before diagnosis (for cases) or in the adolescent/young adulthood period.
It is important in studying the association between physical activity and breast cancer to control for potentially confounding factors to be sure that the association between physical activity and breast cancer is not due to extraneous factors. For example, women who exercise may follow different diets than nonexercisers. If the dietary patterns are related to breast cancer risk, the association between physical activity and breast cancer may be spurious. Most studies controlled for potential confounding factors such as age, reproductive history, and BMI. Since body mass may lie in the causal pathway between physical activity and breast cancer risk, simple adjustment may not give a complete picture. Indeed, some investigators found that risk reduction was limited to the leanest women [23, 34, 39, 40]. Adjustment for dietary macronutrient intake or caloric intake did not confound the physical activity/breast cancer relationship in studies that assessed dietary data [12, 23, 29, 35–37, 41].
Elucidation of the causal pathway between physical activity and cancer risk will help in determining optimum ages to exercise, and the dose, frequency, and intensity of physical activities needed to protect against breast cancer.
Early menarche (before age 12), greater frequency of ovulatory cycles, late first birth or multiparity, lack of lactation, late menopause, greater number of lifetime ovulatory cycles, greater interval between menarche and menopause, and high concentrations of endogenous sex hormones have been found to lead to a greater risk of breast cancer of 20% to >400% [42, 43]. Several of these reproductive and hormonal factors are affected to some degree by physical activity.
In observational studies, girls participating in vigorous sports, such as ballet dancing and running, have been noted to experience high incidences of primary and secondary amenorrhea, delayed menarche, and more irregular cycles, than nonathletic girls [44, 45]. A cross-sectional study of 174 girls aged 14–17 years found that girls who expended 600 or more kilocalories of energy per week (described by the authors as comparable with 2 hours per week in activities such as aerobic exercise classes, swimming, jogging, or tennis) were two to three times more likely than less active girls to have anovulatory menstrual cycles . However, the time course for this association is not clear from the observational data—does physical activity cause anovulatory menstrual cycles or are girls who are not ovulating and therefore experiencing lower hormone levels more likely to engage in physical activity?
In small intervention studies, it has been shown that exercise during the reproductive period of life alters the concentrations of sex hormones [47, 48]. A high-intensity exercise intervention in 28 untrained college women with normal ovulation and luteal adequacy resulted in reversible abnormal luteal function in two-thirds and loss of the luteinizing hormone surge in over half the subjects . The most marked disturbances were observed during the periods of most intense training and in those women who had been randomized to a weight loss (versus weight maintenance) group. It may well be, therefore, that a low body weight is also required to reduce ovulation. Thus, intense prolonged exercise or caloric restriction, or some combination of these, may be required.
Most postmenopausal women produce estrogen through the peripheral conversion (mainly in fat cells) of adrenal androgens to estrogens . Greater physical activity measured through self-reports and by movement monitors has been found to be associated with lower serum concentrations of estradiol, estrone, and androgens in postmenopausal women [50–52] and with greater concentrations of sex-hormone-binding globulin .
One clinical trial has shown that a moderate exercise program reduced endogenous sex hormones in postmenopausal women [54, 55].
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