McTiernan A, Kooperberg C, White E, Wilcox S, Coates R, Adams-Campbell LL, Woods N, Ockene J. Recreational Physical Activity and the Risk of Breast Cancer in Postmenopausal WomenThe Women's Health Initiative Cohort Study. JAMA. 2003;290(10):1331-1336. doi:10.1001/jama.290.10.1331
Author Affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Wash (Drs McTiernan, Kooperberg, and White); Department of Exercise Science, Norman J. Arnold School of Public Health, University of South Carolina, Columbia (Dr Wilcox); Division of Cancer Prevention and Control, NCCDPHP, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Coates); Howard University Cancer Center, Washington, DC (Dr Adams-Campbell); School of Nursing, University of Washington, Seattle (Dr Woods); Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester (Dr Ockene).
Context Women who are physically active have a decreased risk for breast cancer,
but the types, amounts, and timing of activity needed are unknown.
Objective To prospectively examine the association between current and past recreational
physical activity and incidence of breast cancer in postmenopausal women.
Design, Setting, and Patients Prospective cohort study in 74 171 women aged 50 to 79 years who
were recruited by 40 US clinical centers from 1993 through 1998.
Main Outcome Measure Incident invasive and in situ breast cancer.
Results We documented 1780 newly diagnosed cases of breast cancer over a mean
follow-up of 4.7 years. Compared with less active women, women who engaged
in regular strenuous physical activity at age 35 years had a 14% decreased
risk of breast cancer (relative risk [RR], 0.86; 95% confidence interval [CI],
0.78-0.95). Similar but attenuated findings were observed for strenuous physical
activity at ages 18 years and 50 years. An increasing total current physical
activity score was associated with a reduced risk for breast cancer (P = .03 for trend). Women who engaged in the equivalent
of 1.25 to 2.5 hours per week of brisk walking had an 18% decreased risk of
breast cancer (RR, 0.82; 95% CI, 0.68-0.97) compared with inactive women.
Slightly greater reduction in risk was observed for women who engaged in the
equivalent of 10 hours or more per week of brisk walking. The effect of exercise
was most pronounced in women in the lowest tertile of body mass index (BMI)
(<24.1), but also was observed for women in the middle tertile of BMI (24.1-28.4).
Conclusions These data suggest that increased physical activity is associated with
reduced risk for breast cancer in postmenopausal women, longer duration provides
most benefit, and that such activity need not be strenuous.
Women who engage in regular exercise have been shown to have a reduced
risk of breast cancer.1- 4 It
is not clear if physical activity after menopause reduces the risk of breast
cancer or if life-long physical activity is required. The intensity and amount
of exercise needed to reduce risk are unknown, and some studies have suggested
that strenuous activity is needed for risk reduction.1,5 It
is important to determine if moderate physical activity late in life can reduce
risk of breast cancer, since this can be achieved by most women.
We therefore examined the association between recreational physical
activity in adulthood and breast cancer incidence in a large, ethnically and
racially diverse cohort of older women from the Women's Health Initiative
(WHI) Observational Study. Using detailed assessments of physical activity,
we assessed the associations between physical activity (past strenuous activity
at ages 18, 35, and 50 years, and current total physical activity score, hours
per week of strenuous activity, and combined hours per week of moderate and
strenuous activity) and incidence of breast cancer.
The study population consisted of 74 171 women who were enrolled
in the WHI Observational Study, a multicenter, multiethnic cohort of postmenopausal
women aged 50 to 79 years at study entry.6 A
total of 93 676 women were enrolled into the study between October 1993
and December 1998 from 40 US clinical centers. Women were eligible for the
study if they were aged 50 to 79 years, postmenopausal, planned to live in
the clinical center area for at least 3 years, and free of serious health
conditions that might reduce survival during the 3 years (eg, class IV congestive
heart failure, obstructive lung disease requiring supplemental oxygen, or
severe chronic liver or kidney disease). Women were excluded from the present
analysis if they reported a history of breast cancer on study entry or had
missing physical activity or covariate data. The women included in these analyses
represented a diverse cohort of US women including 10 863 (15%) African
American, Hispanic (Mexican American, Puerto-Rican Hispanic, and Cuban Hispanic),
Asian/Pacific Islander (Japanese, Chinese, Hawaiian), and Native American
women.7 Details of the scientific rationale,
design, eligibility requirements, and baseline characteristics of the cohort
have been published previously.6,7
All participants signed informed consent forms. The institutional review
boards at all participating institutions, including the coordinating center,
subcontractors, and clinical centers, approved the study protocols and procedures.
The follow-up rates for medical history updates in years 1, 2, 4, 5,
and 6 (the years in which medical histories were collected by mail) were 96%,
94%, 94%, 95%, and 94%, respectively. As of February 28, 2002, 3.2% of the
women stopped participation or have been lost to follow-up, and 2.7% have
All exposure information in this analysis was collected when women entered
the study. A standardized written protocol, centralized training of clinic
staff, and periodic quality assurance visits by the coordinating center were
used to ensure uniform administration of data collection instruments.
At a required baseline screening clinic visit, participants completed
several self-administered questionnaires, including medical history, reproductive
and menstrual history, health behavior including physical activity and diet,
and family history of select diseases including breast cancer. Staff collected
anthropometric measures (height, weight, waist circumference) and interviewed
participants regarding lifetime use of hormone therapy.
Women first were asked (yes/no) if they usually did strenuous or very
hard exercises (long enough to work up a sweat and make their heart beat fast)
at least 3 times per week at ages 18, 35, and 50 years. Participants then
were asked how often they currently (at study entry) walked outside the home
for more than 10 minutes without stopping, the usual duration, and the speed.
Categories of frequency were rarely/never, 1 to 3 times per month, 1 time
per week, 2 to 3 times per week, 4 to 6 times per week, and 7 or more times
per week. Duration categories were less than 20 minutes, 20 to 39 minutes,
40 to 59 minutes, and 1 hour or more. Four speed categories ranged from less
than 2 mph (casual walking) to more than 4 mph (very fast).
Women then were asked how often they currently (at study entry) exercised
at strenuous levels (that increased heart rate and produced sweating) by checking
categories never, 1, 2, 3, 4, or 5 d/wk or more, and for how long they exercised
at each session by checking categories less than 20 minutes, 20 to 39 minutes,
40 to 59 minutes, or 1 hour or more. Examples provided of strenuous activities
included aerobics, aerobic dancing, jogging, tennis, and swimming laps. Women
were asked similar questions about moderate- and low-intensity physical activities.
Examples provided of moderate-intensity activities included biking outdoors,
using an exercise machine, calisthenics, easy swimming, and popular or folk
dancing; and examples provided of low-intensity activities included slow dancing,
bowling, and golf.
We constructed several composite current physical activity variables.
We imputed the midpoint value for ranges of frequency and duration of exercise
sessions. We multiplied minutes × frequency to create a variable "hours
exercised per week," separately for strenuous, moderate, light, and 3 intensities
of walking. We assigned metabolic equivalent (MET) values for strenuous-,
moderate-, and low-intensity activities as 7, 4, and 3 METs, respectively.8 For mean speed of walking (average [2-3 mph], fast
[3-4 mph], and very fast [>4 mph]), we assigned MET values of 3, 4, and 4.5,
respectively. We computed a current total physical activity variable (MET-hours/week)
by multiplying the MET level for the activity by the hours exercised per week
and summing values for all of the types of activities.
Age at menopause was determined as the youngest age when the participant
experienced any of the following: last menstrual bleeding (all participants
were ≥12 months after last menstrual period), removal of both ovaries,
or beginning of hormone therapy. Age at first birth was calculated as the
age at first pregnancy of 6 months' duration or longer. Total daily kilocalorie
intake and percentage of kilocalories from fat were assessed with a 120-item
semiquantitative food frequency questionnaire developed and tested for the
Among a random sample of 536 participants, second measures of all physical
activity variables were ascertained approximately 10 weeks after baseline.
The test-retest reliability (weighted κ) for the physical activity variables
ranged from 0.53 to 0.72, and the intraclass correlation for the total physical
activity variable was 0.77.7
Study physicians and cancer coders, blinded to exposure status, reviewed
pathology reports, discharge summaries, operative reports, and radiology reports
for all biopsies and surgeries and coded cases according to National Cancer
Institute Surveillance, Epidemiology, and End Results guidelines.10,11
The physical activity questions on past and current activity collected
at study baseline were used in the analyses. Follow-up time for each woman
was accrued from enrollment to the date of diagnosis of breast cancer, death
from a non–breast cancer cause, loss to follow-up, or administrative
censor date (April 30, 2002). Age-adjusted relative risks (RRs) were computed
as the incidence rate in a specific category of activity divided by the incidence
rate in the "no activity" category.
For analyses of past activities, we used "strenuous activity at age
18," "strenuous activity at age 35," and "strenuous activity at age 50," as
binary covariates. For total current physical activity, we created indicator
variables for no activity, 5 MET-h/wk or less, 5.1 to 10 MET-h/wk, 10.1 to
20 MET-h/wk, 20.1 to 40 MET-h/wk, and more than 40 MET-h/wk. For combined
moderate/strenuous exercise we created indicator variables for no activity,
1 h/wk or less, 1.1 to 2 h/wk, 2.1 to 3 h/wk, 3.1 to 4 h/wk, 4.1 to 7 h/wk,
and more than 7 h/wk. For hours of strenuous exercise, the indicator variables
were for no activity, 1 h/wk or less, 1.1 to 2 h/wk, 2.1 to 4 hours h/wk,
and more than 4 h/wk.
We used stratified adjustment and Cox proportional hazards regression
model12 to adjust simultaneously for potential
confounding variables. Categorical variables included age, body mass index
([BMI] calculated as weight in kilograms divided by the square of height in
meters), use of hormone therapy, race, geographic region, income, education,
ever breastfed, hysterectomy status, first-degree relative with breast cancer,
smoking status, parity, age at first birth, number of mammograms in 5 years
before study enrollment, and use of alcohol. Continuous variables included
age at menarche and age at menopause. In a separate analysis, we also adjusted
for daily kilocalorie intake and percentage of calories from fat as continuous
To assess the relative contributions of strenuous and moderate activity
to the total physical activity effect on breast cancer risk, we tested 2 additional
models of total physical activity effect on breast cancer risk including as
adjustment variables percentage of total activities that were strenuous intensity
and percentage of total activities that were moderate or strenuous intensity.
We also assessed the association between these 2 variables and breast cancer
risk in separate models. Analyses were performed using S-Plus (Insightful
Inc, Seattle, Wash).
During a mean length of follow-up of 4.7 years (347 519 woman-years
of observation), we identified 1780 newly diagnosed cases of breast cancer.
Of these, 1537 cases had central coding complete: 85% were invasive (75.5%
stage I, 3.6% stage II), and 85% were estrogen receptor positive.
Women who engaged in strenuous physical activity at least 3 times per
week at age 35 years had a statistically significant decreased risk of breast
cancer of 14% (RR, 0.86; 95% CI, 0.78-0.95) compared with women who did not
engage in this level of activity (Table
1). Results for invasive and in situ cancers were similar, although
the results were statistically significant only for invasive cancers (P = .006, data not shown). Similarly, women who reported
engaging in strenuous physical activity at least 3 times per week at age 50
years had a slight, nonstatistically significant reduction in risk of overall
breast cancer. There was a statistically significant reduction in risk of
invasive cancer of 11% (P = .04) and no difference
in risk of in situ cancer compared with women who did not engage in regular
strenuous activity at this age (data not shown). Regular strenuous activity
at age 18 years was associated with only a marginally decreased risk of breast
Increased amount of total current physical activity (increased MET-hours
per week) was associated with a reduced risk of breast cancer (P = .03 for trend) (Table 2).
Women who exercised on average for 5.1 to 10.0 MET-h/wk (approximately equal
to 1.25-2.5 h/wk of brisk walking or equivalent exercise, or more hours of
lower-intensity exercise) had a statistically significant reduction in risk
of developing breast cancer of 18% compared with sedentary women (RR, 0.82;
95% CI, 0.68-0.97). Women who exercised more than 40 MET-h/wk had a 22% reduction
in risk compared with sedentary women (RR, 0.78; 95% CI, 0.62-1.0). Women
who engaged in more than 7 h/wk of moderate/strenuous physical activity had
a 21% reduced risk of breast cancer compared with sedentary women (RR, 0.79;
95% CI, 0.63-0.99). Increased strenuous physical activity was associated with
a slightly reduced risk for breast cancer that was not statistically significant
(P = .25 for trend).
Adjustment of total activity for either percentage of total activities
that were strenuous intensity or percentage of activities that were moderate
or strenuous intensity did not change the results (data not shown). In that
model, neither percentage of total activities that were strenuous intensity
nor percentage of activities that were moderate or strenuous intensity were
associated with risk of breast cancer (data not shown).
We examined risk of breast cancer associated with physical activity
in tertiles of BMI (Table 3).
Among women in the lowest tertile of BMI (≤24.13), a strong and significant
reduction in risk of breast cancer with increasing level of total current
physical activity was observed (P = .03 for trend).
Women in this BMI group who engaged in 5.1 to 10 MET-h/wk of physical activity
had a 30% reduction in risk for breast cancer (RR, 0.70; 95% CI, 0.51-0.97).
Women who engaged in 20.1 to 40.0 MET-h/wk (approximately 5-10 h/wk of brisk
walking) had a 32% reduction in breast cancer risk (RR, 0.68; 95% CI, 0.51-0.92).
More than 40 MET-h/wk decreased risk even further (RR, 0.63; 95% CI, 0.43-0.93).
Among women in the middle tertile of BMI, increased total physical activity
was associated with a reduced risk of breast cancer, but the associations
were only statistically significant for 5 MET-h/wk or less (RR compared with
no activity, 0.72; 95% CI, 0.53-0.98). Increased total current physical activity
was not associated with a reduced risk of breast cancer among women in the
heaviest tertile of BMI.
Adjustment for either daily kilocalorie intake or percentage of calories
from fat did not change any of these results (data not shown).
We also examined the effects of physical activity on risk of breast
cancer among tertiles of waist circumference (data not shown). Overall, increased
MET-hours per week of total physical activity was associated with decreased
risk of breast cancer across all categories of waist circumference, although
the effect was strongest for the women in the lowest 2 tertiles of waist circumference.
None of the tests for trend was statistically significant.
We examined the effect of physical activity on risk of breast cancer
among several other subgroups including age (50-59, 60-69, 70-79 years), parity
(parous/nulliparous), family history of breast cancer (any/none), and use
of hormone therapy (current/past/never). The reduced risk associated with
increased levels of total physical activity was seen across all categories
of these variables. Results for risk of estrogen-receptor positive tumors
were similar to the results for cases overall (data not shown).
These data from a large prospective cohort of postmenopausal US women
support a protective role of physical activity against breast cancer, particularly
past regular strenuous physical activity at ages 35 and 50 years, and current
increased total physical activity. The greatest associations were observed
for the lightest-weight women, although moderately overweight women also had
benefit from increased total physical activity.
Strengths of the present study include the prospective design, the large
size, the racial and ethnic diversity of the cohort, the detailed assessment
of physical activity, and the uniform and strict criteria for the breast cancer
end points. Other strengths of the study include the high rate of follow-up
and the detailed information about potential confounding variables.
Although the WHI is a multiethnic, multiracial cohort, too few numbers
of cases to report race- or ethnic-specific associations between physical
activity and breast cancer risk were available. We looked at the data for
whites alone and for African Americans alone, the 2 largest racial/ethnic
subgroups of cases, and found that the associations were similar to the overall
analyses (data not shown). We did not collect detailed data on lifetime physical
activity. However, we did collect information about strenuous exercise at
ages 18, 35, and 50 years and found that regular strenuous exercise at the
latter 2 age points was protective against breast cancer. Some of the physical
activity questions grouped exercises together into those that are most often
low, moderate, or vigorous in intensity. If individual women performed activities
at other intensities, there would be misclassification of intensity. The use
of imputed midpoint values for ranges of physical activity data could have
introduced error. Only data on recreational and walking activities were collected.
The resulting nondifferential misclassification of exposure to physical activity
would be expected to bias the risk estimate toward unity, thus the observed
association between increased physical activity and reduced risk for breast
cancer is likely real. Finally, the study population, although representing
more diverse racial, ethnic, and social backgrounds than most previously studied
cohorts, is not an entirely representative cross-section of US women.
Several published cohort studies13- 25 have
investigated the association between physical activity and risk of breast
cancer in postmenopausal women, of which all but a few23,24 found
a reduced risk for breast cancer in women who were classified at the highest
levels of physical activity. The reduction in risk ranged from 10% to 70%
for the most active women. The definition of "most active" varied by study.
A few other cohort and case-control studies have found that risk reduction
associated with physical activity was limited to the leanest or middle-weight
compared with obese postmenopausal women.17,20,26,27 These
results were similar to our findings, although others have found no effect
of adiposity on the association betweeen physical activity and breast cancer.5,18,24,28
Several mechanisms have been proposed to explain the association between
increased physical activity and reduced risk for breast cancer. For exercise
in the postmenopausal years, the most likely mechanism is reduction in body
fat leading to reduced substrate for production of estrogen from androgen
in fat tissue through aromatization.2,29 Physical
activity also could increase levels of sex hormone binding globulin,30 thereby reducing the amount of estradiol in the free,
most biologically active, state. Another potential mechanism is through exercise
reduction of insulin and other growth factors.2,31 Another
analysis of these data showed that increased adiposity was associated with
increased risk for breast cancer, although the effect was limited to women
who had never used hormone therapy.32
The results of this study suggest that physical inactivity may be a
modifiable risk factor for which postmenopausal women can make changes to
reduce their risk of breast cancer. The finding that increased total recreational
and walking physical activity reduces this risk is promising, although it
may not be necessary for women to engage in strenuous activity in their older
years to enjoy the protective effects of exercise. Another promising aspect
of the study is that physical activity reduces risk among women who are using
hormone therapy, a group that is at increased risk for developing breast cancer.33 For those women who choose to continue taking hormone
therapy for control of menopausal symptoms or for prevention of osteoporosis,
it will be welcome information that a simple modification of lifestyle to
increase physical activity can reduce their risk of breast cancer.