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ORIGINAL ARTICLES

Influence of Physical Activity in Different Age and Life Periods on the Risk of Breast Cancer

Friedenreich, Christine M.1,; Courneya, Kerry S.2; Bryant, Heather E.1

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Abstract

There is increasing consistency across studies that physical activity reduces the risk of breast cancer. To date, 23 of 35 studies 1–35 have demonstrated a breast cancer risk reduction among those women who were most active in their occupational and/or recreational activities as compared with inactive women. The physical activity assessments used have varied widely across these studies. None of these previous studies has systematically measured all types of physical activity throughout life to determine which ages or life period(s) may be most etiologically relevant for a reduction in breast cancer risk. 36 The association between physical activity and breast cancer risk is complex, reflecting the complicated and multiple biological mechanisms that are likely operative. 37 These mechanisms include an influence on endogenous sexual and metabolic hormone levels and growth factors; energy balance and prevention of obesity and weight gain; and, possibly, immune function. 37 By identifying which time periods in life are most associated with a breast cancer risk reduction, a better understanding of which biological mechanisms may be involved could be elucidated. Furthermore, when developing physical activity programming for women, it is important to know when in life physical activity needs to be performed for a risk reduction to occur and whether activity needs to be sustained in life or whether activity taken up later in life can also have a beneficial effect. This study was designed specifically to examine how physical activity done at different time periods in a woman’s life is related to the risk of developing breast cancer.

Subjects and Methods

We conducted a population-based case-control study in Alberta between August 1995 and August 1997. 38,39 Women with incident, histologically confirmed in situ or invasive breast cancer were identified directly from the Alberta Cancer Registry, a population-based cancer registry that has an estimated 95% case ascertainment rate. 40 Cases were eligible for the study if they were residents of Alberta, were 80 years of age or younger, and were able to speak English and to complete an in-person interview. During this study period, 1,764 cases were identified as potentially eligible; of these women, 182 were ineligible for the study. Reasons for ineligibility included physician refusal (N = 32), language barrier (N = 38), having moved or had the telephone disconnected (N = 22), nonavailability during the study period (N = 84), and death (N = 6). Of the remaining 1,582 eligible women who could be contacted for an interview, 1,239 (78.3%) completed an in-person interview, 341 refused the interview, and 2 had an incomplete interview.

Female controls were identified through random-digit dialing using the Waksberg method. 41 Controls were frequency matched to cases on age (±5 years) and place of residence (urban/rural). To be eligible for the study, controls had to be free of any cancer diagnosis excluding non-melanoma skin cancer. Randomly generated telephone numbers in Alberta were called to determine whether they were residence numbers and to identify any possibly eligible women. The telephone recruiters identified 2,265 women as potentially eligible (within the age range being sought for the study). Of these 2,265 women, 684 refused participation and 1,581 women agreed to receive a study package and were called by the interviewers to set up an appointment. A total of 68 women could not be interviewed because they were not eligible (N = 40), had moved or had their telephone disconnected (N = 19), or were not available (N = 9), leaving 1,513 who could be interviewed. Interviews were completed with 1,241 women (82% of the eligible and available women who had agreed to receive the study package). The overall response rate for the controls was 56.5% (1,241 interviews completed out of 2,197 eligible and available women). The final dataset for analysis included 1,233 cases and 1,237 controls; six cases and four controls had to be removed because of too many missing values in their data.

Data Collection

The cases’ physicians were sent letters informing them of the study and seeking permission to contact the patients. If the physicians did not decline permission for patient contact within 2 weeks of the letters being sent to them, the cases were sent a study package. The package included a cover letter describing the study, a consent form, and two recall calendars developed specifically for this study. Interviewers contacted the study subjects by telephone and set up an in-person interview with each one that usually occurred in the respondent’s home.

Information gathered during the interview included: menstrual and reproductive history, hormone use history, mammography history, personal history of breast disease, breast biopsies and personal history of cancer, family history of cancer, lifetime physical activity patterns, dietary intake during the reference year, alcohol consumption, smoking habits, demographic characteristics, and current and past anthropometric measurements. All data obtained were up to the date of diagnosis for the cases and a comparable date for the controls. Diet during the reference year (that is, year preceding diagnosis in cases and comparable year period for controls) was assessed with the National Cancer Institute Block food frequency questionnaire. 42 Current height, weight, and waist and hip circumferences were measured by the interviewers at the end of the interview using standardized methods.

Lifetime physical activity was assessed using a questionnaire developed and tested for reliability in a pilot study that preceded the case-control study. 43 This questionnaire assessed occupational (including means of transportation to and from work if by bicycle or walking), household, and recreational activity separately throughout a respondent’s lifetime. The frequency, duration, and intensity of the activity were recorded. For intensity, both the respondent’s self-perceived intensity levels and the intensity values as designated in the Compendium of Physical Activities 44 were used.

Two recall calendars, one focusing on educational and occupational activities and the other on major life events, were mailed to the participants before the interview. These calendars had been specifically designed for this study and pilot-tested with the questionnaire. They were used as memory aids for the respondents to improve their long-term recall of the physical activities throughout life. The interviewers used cognitive interviewing methods 45,46 to assist the respondents in answering the questions. Quality control of the interviewers’ methods was ensured by regular meetings of the research team and monitoring of interviews by the study coordinator. Furthermore, interviewers observed each other’s interviews throughout the study to ensure that they were using the same interviewing methods.

Lifetime total physical activity was estimated for this study. From the questionnaire, the frequency and duration of occupational, recreational, and household activities were assessed by recording the number of years, months per year, weeks per month, days per week, and hours per day that each activity was performed. The intensity of the activity was estimated by the participant as sedentary (used for occupational activities only), light, moderate, or heavy (that is, self-reported intensity). Definitions for each intensity level by type of activity were provided with examples for the study participants. In general, light activities were defined as those activities that require minimal physical effort and could be done standing or with slow walking. Moderate activities were defined as activities that were not exhausting, that increased the heart rate slightly, and that may have caused some light perspiration. Heavy activities were defined as activities that increased the heart rate and caused heavy sweating. In addition to self-reported intensities, a specific MET value was assigned to each reported activity on the basis of the description of the activity. A MET is defined as the ratio of the associated metabolic rate for a specific activity as compared with the resting metabolic rate. 47 The MET values used were abstracted from the Compendium of Physical Activities. 44 The main exposure variable used in this analysis was the average MET-hours per week per year spent in total lifetime physical activity over the respondent’s lifetime, which was estimated as the sum of occupational, household, and recreational activity. An example for this study would be an average of 100 MET-hours per week per year reported by a study subject. This individual could accumulate this level of activity by doing 3 hours of recreational activity of moderate-intensity activity (that is, 5 METs) per week, 30 hours of light occupational activity (that is, 2 METs) per week, and 10 hours of light household activity (that is, 2.5 METs) per week.

Several parameters of physical activity need to be considered when examining the impact of activity on risk and when developing public health recommendations. Each of these parameters has an independent effect that can be manipulated separately when developing exercise prescriptions for risk reduction purposes. These parameters include the type of activity (ie, occupational, household, recreational), the dose of activity (ie, the frequency, intensity, and duration) and the time period in life when the activity was performed. Our first analysis examined each type of activity separately and all activities combined in a lifetime total activity variable. 38 The second analysis examined the impact of total physical activity done at different time periods in life and is the subject of the present paper. The third analysis examines what frequency, duration, and intensity of total physical activity are related to reduction in risks of breast cancer. 39

Statistical Analysis

To examine how the risk of breast cancer was influenced by physical activity performed at different time periods in a respondent’s life, we conducted two separate analyses. For the first analysis, the respondent’s lifetime activity was divided into activity done during the periods 0–17, 18–24, 25–44, 45–64, and 65–85 years of age. We chose these age groups to correspond with those most commonly used for investigations of physical activity and health outcomes. For the second analysis, we divided lifetime activity into biologically relevant life periods: birth to menarche, menarche to first full-term pregnancy, first full-term pregnancy to menopause, and menopause to reference year. The first analysis included all women who had reached each of the different age periods. For the second analysis, if a woman had not experienced the biological event (for example, pregnancy or menopause), she was excluded from that particular stratum for the analysis.

We conducted an additional set of analyses for age group and life period by stratifying the study population on menopausal status. Women were classified as postmenopausal if they stated that they were postmenopausal (N = 641) or reported that they had stopped menstruating for more than a year by the reference date and their age was 50 years or more (N = 201). We considered those women to be postmenopausal if their hysterectomy occurred after menopause (N = 40), if they had a bilateral oophorectomy before menopause (N = 240), if they had symptoms of menopause that occurred after their hysterectomy (N = 278), or if they were currently 55 years of age or older (N = 61). A total of 1,533 women were postmenopausal and 937 were premenopausal.

To examine further the influence of sustained activity throughout life, we conducted an additional analysis to stratify women according to the level of activity before and after menopause. Activity levels were divided into tertiles, rather than quartiles as had been done for previous analyses, to decrease the number of women who would be removed from the subsequent analysis. We categorized women into four groups according to their total physical activity levels before and after menopause. Never-exercisers were women who stayed in the lowest tertile of activity before and after menopause. Late-life exercisers were women who were in the lowest activity tertile before menopause and in the highest tertile after menopause. Early-life exercisers were women who were in the highest activity tertile before menopause and then in the lowest tertile after menopause. Finally, lifelong exercisers were women who were in the highest tertiles of activity before and after menopause. The association with breast cancer for all of these additional physical activity variables was modeled as follows.

We estimated the average total physical activity levels of cases and controls for the six age periods and four life periods that were defined for this study to examine case-control differences. We categorized total physical activity into quartiles according to the distribution of the variables among the controls, and we used unconditional logistic regression modeling to estimate the odds ratio (ORs) associated with breast cancer for activity at these different age and life periods. We constructed age-adjusted and multivariable-adjusted models with a full examination of confounding by other established and putative risk factors. We considered as confounders age, body mass index [weight (kg) per height squared (m2)], waist-hip ratio, marital status, educational level, ethnicity, first-degree family history of breast cancer, whether menstruation had ever ceased for reasons besides pregnancy, irregular menstrual cycles, ever-oral contraceptive use, duration of oral contraceptive use, parity and gravidity, ever-breast feeding, ever-hormone replacement therapy use, duration of hormone replacement therapy use, type of hormone replacement therapy, history of benign breast disease, previous benign breast biopsy, ever-alcohol consumption, ever-cigarette smoking, current cigarette smoking, total pack-years of smoking, total caloric intake, and daily dietary fat intake. We adjusted the final models for waist-hip ratio (in quartiles), education level achieved (in quintiles), ever-use of hormone replacement therapy, history of benign breast disease, first-degree family history of breast cancer, current cigarette smoking, and ever-alcohol consumption. All other variables were eliminated, as they did not influence the overall fit of the logistic regression model. The analyses were also stratified by menopausal status, because effect modification by this factor was found in these data.

Results

The study population has been described in detail previously. 38 In brief, these women were on average 56 years of age, mainly white, married, with more than half of the population educated beyond high school. The case and control populations were similar for the sociodemographic, anthropometric, medical, and reproductive characteristics considered. The average total physical activity levels of cases and controls were similar when comparing means for total lifetime activity and by age periods in years and by life periods (Table 1). After 45 years of age (for the age period analysis) or after the first full-term pregnancy (for the life period analysis), controls had somewhat higher lifetime total activity levels.

Table 1
Table 1:
Average Lifetime Total Physical Activity by Age and Life Periods, N = 2,470

The difference in total physical activity levels between cases and controls with increasing age became somewhat more apparent when examining the risk of breast cancer by age periods (Table 2) and life periods (Table 3). The lowest relative risks observed occurred for activity performed between 65 and 85 years of age, for which we found an OR of 0.75 [95% confidence interval (95% CI) = 0.45–1.18] for the highest activity vs lowest activity quartile. We also found low relative risks for activity done between menopause and the reference year [OR = 0.70 (95% CI = 0.52–0.95)]. We saw no apparent risk decrease for the earlier ages or life periods up to age at first full-term pregnancy.

Table 2
Table 2:
Odds Ratios for Total Physical Activity, by Age Periods, N = 2,470
Table 3
Table 3:
Odds Ratios for Total Physical Activity, by Life Periods, N = 2,470

We present the analyses stratified by menopausal status for the age period analysis in Table 4, whereas we do not show those for the life period analysis, because these overlap partially with those already presented in Table 3. The risks for breast cancer were consistently reduced, for each age period considered, among the postmenopausal but not premenopausal women. These results corroborate those found for the analysis of lifetime total physical activity stratified by menopausal status and also presented in Table 4. Breast cancer risks were particularly reduced for postmenopausal women in the highest category of activity during their childhood and adolescence (0–17 years) and after 45 years of age (Table 4).

Table 4
Table 4:
Odds Ratios for Total Physical Activity, by Age Periods, by Menopausal Status, N = 2,470

We repeated these analyses for type of activity (that is, occupational, household, and recreational activity) (data not shown). The risk reductions that were found for total lifetime activity were attributable mainly to risk decreases for occupational and household activity. For the period from menopause to the reference year, the OR for highest vs lowest quartile for occupational activity was 0.70 (95% CI = 0.51–0.95), for household activity it was 0.76 (95% CI = 0.56–1.03), and for recreational activity it was 0.90 (95% CI = 0.67–1.22).

The final analysis examined patterns of activity throughout life by characterizing women as either nonexercisers, early-life exercisers, late-life exercisers, and lifelong exercisers (Table 5). Women who were in the top tertile of activity before menopause but who were no longer in that category after menopause (early-life exercisers) had an OR of 0.93 (95% CI = 0.56–1.55). Women who moved into the top tertile of activity after menopause (late-life exercisers) had an OR of 0.60 (95% CI = 0.33–1.11), and women in the top tertiles of activity before and after menopause (lifelong exercisers) had an OR of 0.58 (95% CI = 0.41–0.83).

Table 5
Table 5:
Odds Ratios for Total Physical Activity by Lifetime Pattern of Physical Activity, N = 713

Discussion

This study is the first one to assess physical activity systematically throughout life to determine which age and life period(s) are most associated with a relative reduction in breast cancer risk. We found that the largest risk reductions occurred in the older age and life periods. Specifically, total physical activity was associated with a 30% decrease in breast cancer risk for activity between menopause and the reference year or a 25% risk reduction for activity between 65 and 85 years of age. We classified women according to their activity patterns before and after menopause and found that sustained activity throughout life was associated with the greatest risk decreases and that activity after menopause contributed the largest component of this risk decrease.

A possible selection bias may have been introduced into this large, population-based, case-control study because the controls had a lower response rate than the cases. To address the issue of selection bias, we compared controls with a sample of female Albertans 25 years of age or older (N = 6,146) who were included in the National Population Health Survey, the 1996–1997 survey that was conducted by Statistics Canada. 48 In that survey, respondents were asked about their frequency and duration of current recreational activities. Controls sampled in our study were found to have current recreational activity levels comparable with those sampled within the Alberta component of the National Population Health Survey.

Recall bias is a possible problem in any case-control study. In this investigation, it was less likely that biased recall of physical activity could have influenced the results, because physical activity was one of several risk factors that were measured and no particular emphasis was placed on this risk factor. Furthermore, limited publicity surrounding physical activity as a means for the primary prevention of breast cancer had occurred at the time of the data collection for this study.

Misclassification of exposure is also a possibility in this investigation, because the respondents were asked to report detailed lifetime physical activity patterns. The effect of misclassification of physical activity would have been to decrease the ability of the study to demonstrate an effect of physical activity on breast cancer risk (nondifferential misclassification bias).

This study can be compared with 15 studies 10,15,17,18,20,21,23,24,26,27,29,30,32,33,35 that specifically examined and reported effects for selected age periods over a lifetime. Six 27,20,23,29,32,35 found risk reductions for activity performed early in life, and four 20,21,26,32 found that activity done later in life decreased breast cancer risk. No clear pattern is apparent from these studies regarding the time during life that physical activity is most etiologically relevant. These studies, however, measured only a few time windows, and some measured activity at only one time period.

Three other studies did attempt a more comprehensive measure of lifetime activity. 15,30,33 Bernstein et al15 recorded recreational activity from menarche to 40 years of age, and Carpenter et al30 recorded recreational activity to 64 years of age. Neither of these studies included occupational or household activity. Verloop et al33 assessed recreational activity in three time windows: between 10–20 years of age, between 20 years of age and up to 5 years before the diagnosis, and within 5 years preceding the diagnosis. Verloop et al33 also measured usual lifetime recreational activity and title of longest job held. The strongest relative risk reductions in the studies by Bernstein et al15 and Carpenter et al30 were found for the measures of overall lifetime physical activity. In their case-control study of premenopausal women, Bernstein et al15 observed a reduction in risk for activity during the 10 years after menarche, whereas a comparable reduction for that period was not observed in the case-control study of postmenopausal women. 30 In the latter study, 30 a higher recreational level of activity during the 10-year perimenopausal and early postmenopausal period moderately decreased the risk of breast cancer. 30 Verloop et al33 found the greatest relative risk reductions for activity in the intermediate time window (that is, between 20 years of age and up to 5 years before the diagnosis). Thus, from the two studies that measured lifetime activity, 15,30 it appears that the strongest predictor of a decrease in breast cancer risk was the number of years of recreational activity. Because the age groups of the study populations for these two studies did not overlap, it is difficult to make any generalizations on which age periods in life are most important for an association between physical activity and breast cancer.

The only other published study that attempted to examine changes in activity pattern throughout life was the study by Verloop et al.33 They cross-tabulated their study subjects by activity early in life (between 10 and 20 years of age) and by activity after 20 years of age. Women who were physically active early in life but then became inactive (comparable with our so-called early-life exercisers) had a slightly reduced risk of breast cancer (OR = 0.83; 95% CI = 0.60–1.16) when compared with nonexercising women. Women who were inactive in early life and became active in later life (that is, late-life exercisers) or who were always active (that is, lifelong exercisers) had comparable risk reductions for breast cancer [OR = 0.65 (95% CI = 0.47–0.89) and OR = 0.68 (95% CI = 0.53–0.87), respectively]. In that study, the sample of women who started recreational activities after 30 years of age comprised fewer than 10% of all active women. Hence, the investigators were unable to determine whether a risk reduction also existed for activity started later in life. These data suggest that activity done in any time period in life is etiologically relevant. The data also support the observations made by Carpenter et al30 that activity needed to be sustained throughout life to provide a lifetime reduction in breast cancer risk.

Our findings reinforce these studies. We observed the greatest decreases in relative risk for total physical activity between menopause and the reference year. The women who experienced breast cancer risk reductions at older ages were likely to be those who had maintained a higher level of activity throughout their lives. This hypothesis is supported by the stratified analysis that we conducted on total physical activity before and after menopause, because women who were active in both of these broad life periods (the lifelong exercisers) experienced the greatest risk reductions compared with women who did not achieve consistently high levels of activity throughout their lives (that is, the late-life exercisers and early-life exercisers).

An alternative explanation for our study results is that there was better recall for more recent activity and that, consequently, there was less measurement error for activity performed since menopause. Thus, the stronger effects observed for more recent activity may be attributable to better measurement of activity. This hypothesis is somewhat supported by the reliability testing that we did on our Lifetime Total Physical Activity Questionnaire. 42 The highest correlation coefficients, observed for the test-retest reliability for different time periods in life, was for activity done at more than 50 years of age, whereas the lowest correlations were for activity done when younger than 18 years of age. Nevertheless, activity in the reference year had lower test-retest reliability than activity over a lifetime or activity after 50 years of age. Hence, the results that we observed in this study are not likely to be attributable entirely to better measurement of physical activity performed in the recent past.

The results of this analysis can be combined with the findings from the two other analyses done of different parameters of physical activity in this case-control study to develop overall summary of the impact of physical activity on breast cancer risk in this particular population. 38,39 This study found that total lifetime physical activity reduced the risk of breast cancer in postmenopausal women by 30%, while no risk decreases were observed for premenopausal women. When examining the risk by type of activity, the risk reduction observed was attributable to occupational and household activity but not recreational activity. 38 Greater risk reductions were also observed among the postmenopausal women in the highest quartile of lifetime total physical activity who were non-smokers, non-alcohol drinkers, and nulliparous. 38 When examining the association by dose of activity needed for a risk reduction, 39 we observed that moderate intensity activities were associated with the greatest decreases, while light and vigorous intensity activities were not associated with notable risk reductions. When the independent effects of the frequency and duration of activity were examined, a clearer risk reduction was observed for these parameters of activity than had been found for intensity of activity. Hence, it appears from this study that sustained, moderate-intensity total physical activity confers an approximate 30% reduction in postmenopausal breast cancer risk and that occupational and household activities are particularly relevant to achieve this decreased risk.

A number of hypothesized biological mechanisms have been proposed for physical activity in breast cancer etiology, but the two main hypotheses involve the influence of activity on hormone levels and energy balance. 37 Physical activity has been shown to increase age at menarche and increase anovulation and irregular menstrual cycles, thereby decreasing the overall exposure to endogenous estrogens. 49 Physical activity can also influence breast cancer risk by decreasing weight gain, particularly after menopause. Postmenopausal obesity has been identified as a risk factor for breast cancer, 50 and physical activity is an integral component in maintaining energy balance. In this study, we found only limited support for an influence of high physical activity levels on reducing breast cancer risk for activity done during adolescence. There was more support for an effect of activity done later in life, particularly after menopause. Thus, it appears from these results that maintaining a constant weight, particularly by avoiding obesity and central adiposity after menopause through physical activity, may be particularly etiologically important.

We thank Kathleen Douglas-England for study coordination; Zeva Mah, Laura Godard, Mila Belic, and Doreen Mandziuk for assistance with the research project; Valerie Hudson for data cleaning; Victoria Stagg for data processing; Xuechao Chen for data analysis; Lisa Alexander, Selena Chow, Pearl Cooke, Shelley Cooper, Linda Davison, Marilyn Dickson, Carrie Lavis, Doreen Mandziuk, Hijin Park, Jodi Parrotta, and Nicole Slot for interviewing the study participants; and Colleen Maxwell for providing the data analysis of the National Population Health Survey data.

References

1. Frisch RE, Wyshak G, Albright NL, Albright TE, Schiff I, Witschi J, Marguglio M. Lower prevalence of breast cancer and cancers of the reproductive system among former college athletes compared to non-athletes. Br J Cancer 1985; 52: 885–891.
2. Vena JE, Graham S, Zielezny M, Brasure J, Swanson MK. Occupational exercise and risk of cancer. Am J Clin Nutr 1987; 45: 318–327.
3. Pukkala E, Poskiparta M, Apter D, Vihko V. Life-long physical activity and cancer risk among Finnish female teachers. Eur J Cancer Prev 1993; 2: 369–376.
4. Zheng W, Shu XO, McLaughlin JK, Chow W-H, Gao YT, Blot WJ. Occupational physical activity and the incidence of cancer of the breast, corpus uteri, and ovary in Shanghai. Cancer 1993; 71: 3620–3624.
5. Dorgan JF, Brown C, Barrett M, Splansky GL, Kreger BE, D’Agostino RB, Albanes D, Schatzkin A. Physical activity and risk of breast cancer in the Framingham heart study. Am J Epidemiol 1994; 139: 662–669.
6. Steenland K, Nowlin S, Palu S. Cancer incidence in the National Health and Nutrition Survey I follow-up data: diabetes, cholesterol, pulse and physical activity. Cancer Epidemiol Biomarkers Prev 1995; 4: 807–811.
7. Fraser GE, Shavlik D. Risk factors, lifetime risk, and age at onset of breast cancer. Ann Epidemiol 1997; 7: 375–382.
8. Thune I, Brenn T, Lund E, Gaard M. Physical activity and the risk of breast cancer. N Engl J Med 1997; 336: 1269–1275.
9. Sesso HD, Paffenbarger RS Jr, Lee I-M. Physical activity and breast cancer risk in the College Alumni Health Study (United States). Cancer Causes Control 1998; 9: 433–439.
10. Rockhill B, Willett WC, Hunter DJ, Manson JE, Hankinson SE, Spiegelman D, Colditz GA. Physical activity and breast cancer risk in a cohort of young women. J Natl Cancer Inst 1998; 90: 1155–1160.
11. Calle EE, Murphy TK, Rodríguez C, Thun MJ, Heath CW Jr. Occupation and breast cancer mortality in a prospective cohort of US women. Am J Epidemiol 1998; 148: 191–197.
12. Rockhill B, Willett WC, Hunter DJ, Manson JE, Hankinson SE, Colditz GA. A prospective study of recreational physical activity and breast cancer risk. Arch Intern Med 1999; 159: 2290–2296.
13. Wyshak G, Frisch RE. Breast cancer among female college athletes compared to non-athletes: a 15-year follow-up. Br J Cancer 2000; 82: 726–730.
14. Dosemeci M, Hayes RB, Vetter R, Hoover RN, Tucker M, Engin K, Unsal M, Blair A. Occupational physical activity, socioeconomic status, and risk of 15 cancer sites in Turkey. Cancer Causes Control 1993; 4: 313–323.
15. Bernstein L, Henderson BE, Hanisch R, Sullivan-Halley J, Ross RK. Physical exercise and reduced risk of breast cancer in young women. J Natl Cancer Inst 1994; 86: 1403–1408.
16. Friedenreich CM, Rohan TE. Physical activity and risk of breast cancer. Eur J Cancer Prev 1995; 4: 145–151.
17. Mittendorf R, Longnecker MP, Newcomb PA, Dietz AT, Greenberg ER, Bogdan GF, Clapp RW, Willett WC. Strenuous physical activity in young adulthood and risk of breast cancer (United States). Cancer Causes Control 1995; 6: 347–353.
18. Taioli E, Barone J, Wynder EL. A case-control study on breast cancer and body mass. Eur J Cancer 1995; 31A: 723–728.
19. Hirose K, Tajima K, Hamajima N, Inoue M, Takezaki T, Kuroishi T, Yoshida M, Tokudome S. A large-scale, hospital-based case-control study of risk factors of breast cancer according to menopausal status. Jpn J Cancer Res 1995; 86: 146–154.
20. D’Avanzo B, Nanni O, La Vecchia C, Franceschi S, Negri E, Giacosa A, Conti E, Montella M, Talamini R, Decarli A. Physical activity and breast cancer risk. Cancer Epidemiol Biomarkers Prev 1996; 5: 155–160.
21. McTiernan A, Stanford JL, Weiss NS, Daling JR, Voigt LF. Occurrence of breast cancer in relation to recreational exercise in women age 50–64 years. Epidemiology 1996; 7: 598–604.
22. Coogan PF, Clapp RW, Newcomb PA, Mittendorf R, Bogdan G, Baron JA, Longnecker MP. Variation in female breast cancer risk by occupation. Am J Ind Med 1996; 30: 430–437.
23. Hu YH, Nagata C, Shimizu N, Kaneda N, Kashiki Y. Association of body mass index, physical activity, and reproductive histories with breast cancer: a case-control study in Gifu, Japan. Breast Cancer Res Treat 1997; 43: 65–72.
24. Chen CL, White E, Malone KE, Daling JR. Leisure-time physical activity in relation to breast cancer among young women (Washington, United States). Cancer Causes Control 1997; 8: 77–84.
25. Coogan PF, Newcomb PA, Clapp RW, Trentham-Dietz A, Baron JA, Longnecker MP. Physical activity in usual occupation and risk of breast cancer (United States). Cancer Causes Control 1997; 8: 626–631.
26. Mezzetti M, La Vecchia C, Decarli A, Boyle P, Talamini R, Franceschi S. Population attributable risk for breast cancer: diet, nutrition, and physical exercise. J Natl Cancer Inst 1998; 90: 389–394.
27. Gammon MD, Schoenberg JB, Britton JA, Kelsey JL, Coates RJ, Brogan D, Potischman N, Swanson CA, Daling JR, Stanford JL, Brinton LA. Recreational physical activity and breast cancer risk among women under age 45 years. Am J Epidemiol 1998; 147: 273–280.
28. Ueji M, Ueno E, Osei-Hyiaman D, Takahashi H, Kano K. Physical activity and the risk of breast cancer: a case-control study of Japanese women. J Epidemiol 1998; 8: 116–122.
29. Marcus PM, Newman B, Moorman PG, Millikan RC, Baird DD, Qaqish B, Sternfeld B. Physical activity at age 12 and adult breast cancer risk (United States). Cancer Causes Control 1999; 10: 293–302.
30. Carpenter CL, Ross RK, Paganini-Hill A, Bernstein L. Lifetime exercise activity and breast cancer risk among post-menopausal women. Br J Cancer 1999; 80: 1852–1858.
31. Coogan PF, Aschengrau A. Occupational physical activity and breast cancer risk in the Upper Cape Cod Cancer Incidence Study. Am J Ind Med 1999; 36: 279–285.
32. Levi F, Pasche C, Lucchini F, La Vecchia C. Occupational and leisure time physical activity and the risk of breast cancer. Eur J Cancer 1999; 35: 775–778.
33. Verloop J, Rookus MA, van der Kooy K, van Leeuwen FE. Physical activity and breast cancer risk in women aged 20–54 years. J Natl Cancer Inst 2000; 92: 128–135.
34. Moore DB, Folsom AR, Mink PJ, Hong C-P, Anderson KE, Kushi LH. Physical activity and incidence of postmenopausal breast cancer. Epidemiology 2000; 11: 292–296.
35. Shoff SM, Newcomb PA, Trentham-Dietz A, Remington PL, Mittendorf R, Greenberg ER, Willett WC. Early-life physical activity and postmenopausal breast cancer: effect of body size and weight change. Cancer Epidemiol Biomarkers Prev 2000; 9: 591–595.
36. Friedenreich CM, Thune I, Brinton LA, Albanes D. Epidemiologic issues related to the association between physical activity and breast cancer. Cancer 1998; 83: 600–610.
37. Hoffman-Goetz L, Apter D, Demark-Wahnefried W, Goran MI, McTiernan A, Reichman ME. Possible mechanisms mediating an association between physical activity and breast cancer. Cancer 1998; 83: 621–628.
38. Friedenreich CM, Bryant HE, Courneya KS. Case-control study of lifetime physical activity and breast cancer risk. Am J Epidemiol 2001; 154: 336–347.
39. Friedenreich CM, Courneya KS, Bryant HE. Relation between intensity of physical activity and breast cancer risk reduction. Med Sci Sports Exerc 2001;33:(in press).
40. Chen VW, Wu XC, Andrews PA, eds. Cancer in North America, 1991–1995. Incidence. Vol. 1. Sacramento: North American Association of Cancer Registries, 1999.
41. Waksberg J. Sampling methods for random digit dialing. J Am Stat Soc 1978; 73: 40–46.
42. Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L. A data-based approach to diet questionnaire testing and design. Am J Epidemiol 1986; 124: 453–469.
43. Friedenreich CM, Courneya KS, Bryant HE. The Lifetime Total Physical Activity Questionnaire: development and reliability. Med Sci Sports Exerc 1998; 30: 266–274.
44. Ainsworth BE, Jacobs DR Jr, Leon AS, Haskell WL, Montoye HJ, Sallis JF, Paffenbarger RS Jr. Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 1993; 25: 71–80.
45. Jobe JB, Mingay DJ. Cognitive research improves questionnaires. Am J Public Health 1989; 79: 1053–1055.
46. Willis G. Cognitive Interviewing and Questionnaire Design: A Training Manual. National Center for Health Statistics Working Paper Series. Hyattsville, MD: National Center for Health Statistics, 1994.
47. Anshel MH, Freedson P, Hamill J, Haywood K, Horwat M, Plowman SA. Dictionary of the Sports and Exercise Sciences. Champaign IL: Human Kinetics Publications, 1991.
48. Statistics Canada. National Population Health Survey 1996–97: Household Component User’s Guide for the Public Use Microdata Files. Cat. No. 82 M0009GPE. Ottawa: Ministry of Industry, 1998.
49. Bernstein L, Ross RK, Lobo RA, Hanisch R, Krailo MD, Henderson BE. The effects of moderate physical activity on menstrual cycle patterns in adolescence: implications for breast cancer prevention. Br J Cancer 1987; 55: 681–685.
50. Ballard-Barbash R. Energy balance, anthropometry, and cancer. In: Heber D, Blackburn GL, Go VLW, eds. Nutritional Oncology. New York: Academic Press, 1999; 137–151.
Keywords:

breast neoplasms; exercise; case-control study; prevention; menopause; age; life stages

© 2001 Lippincott Williams & Wilkins, Inc.