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Journal of Exercise Science & Fitness 10 (2012) 1e7

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Review article

Physical activity and breast cancer risk

Paul D. Loprinzi a,*, Bradley J. Cardinal b, Ellen Smit c, Kerri M. Winters-Stone d
a
Department of Exercise Science, Donna & Allan Lansing School of Nursing & Health Sciences, Bellarmine University, Louisville, KY, USA
b
Program in Exercise and Sport Science, School of Biological and Population Health Sciences, College of Public Health and Human Sciences,
Oregon State University, Corvallis, OR, USA
c
Program in Epidemiology, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University,
Corvallis, OR, USA
d
School of Nursing, Oregon Health & Science University, Portland, OR, USA
Received 26 May 2011; revised 27 July 2011; accepted 7 September 2011
Available online 5 June 2012

Abstract

To provide the current evidence linking physical activity to breast cancer risk, the objectives of this review were twofold: (1) to review the
epidemiological literature examining the relationship between physical activity and breast cancer risk; and (2) to summarize the mechanisms
through which physical activity can influence risk. A review of the literature was conducted to identify studies that addressed these two
objectives. Of the 76 studies reviewed, 40 (53%) reported a protective effect of physical activity on breast cancer risk. The protective effects of
physical activity on breast cancer risk are likely to be through changes in sex hormone levels, immune function, adiposity, and insulin-related
hormones. To achieve the greatest reduction in risk of breast cancer, regular participation in physical activity should begin in childhood and
persist throughout the lifespan.
Copyright Ó 2012, The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords: Epidemiology; Exercise; Survivors; Women

Introduction Fortunately, advances in medical therapy have led to

Except for non-melanoma skin-related cancer, breast
cancer is the most common form of cancer among women.1 In
2006, 191,410 women were diagnosed with breast cancer in
the USA.1 According to recent estimates, about 12% of
women in the general population will develop breast cancer in
their lifetime. Some women are inherently at risk for devel-
oping breast cancer due to hereditary factors, such as muta-
tions in tumor suppressor genes (e.g., BRCA1 and BRCA2).2
Among women who have inherited a mutation in the BRCA1
or BRCA2 gene, up to 60% will develop breast cancer.2,3
Though comparatively rare, males are also at risk for devel-
oping breast cancer, with 2140 new cases reported in 2011.
* Corresponding author. Bellarmine University, Department of Exercise
Science, Louisville, KY 40205, USA. Tel.: þ1 502 272 8008; fax: þ1 502 272
7602.
E-mail address: ploprinzi@bellarmine.edu (P.D. Loprinzi).
improvements in survival rates among those diagnosed with
breast cancer. For example, approximately, 89% of women
diagnosed with breast cancer will live at least 5-years post-diag-
nosis4; however, those surviving up to 20e30 years post-
diagnosis are still at a higher risk for breast cancer recurrence
than women never diagnosed with cancer.5 Notwithstanding these
improvements in breast cancer therapy, new breast cancer-
fighting therapies are costly and are associated with significant
side effects.6,7 Consequently, additional adjuvant therapies that
complement traditional systemic therapies are needed. One rela-
tively low-cost, safe, and effective strategy to complement current
adjuvant therapies, and possibly aid in the primary prevention
of breast cancer, includes the promotion of physical activity.
To provide an up-to-date delineation of the relationship
between physical activity and breast cancer risk,8 and to discuss
candidate mechanisms responsible for this relationship, this
manuscript evaluates the current research literature that

doi:10.1016/j.jesf.2012.04.004
1728-869X/$ - see front matter Copyright Ó 2012, The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd. This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
2 P.D. Loprinzi et al. / Journal of Exercise Science & Fitness 10 (2012) 1e7
investigates the link between physical activity and breast cancer
risk, and discusses the mechanisms through which physical
activity may reduce cancer risk. The paper concludes by
summarizing the implications for health care professionals.
Methods
An extensive review of the epidemiological literature on the
effect of physical activity on breast cancer risk was conducted
through PubMed, using the following keywords: physical
activity, exercise, and breast cancer.
To identify the biological mechanisms thought to influence
the association between physical activity and breast cancer
risk, a PubMed search was conducted using the following
keywords: exercise, physical activity, breast cancer, and
mechanisms. Articles that had these keywords in the title or
abstract were obtained and reviewed. The discussion section of
related studies were reviewed and manual searches of the
reference lists of the articles retrieved were also performed.
Only English language manuscripts were included.
Level of evidence
The effect of physical activity on breast cancer risk was
categorized using the following coding scheme: (1) “protective
effect”, if a significant inverse association was reported; (2)
“non-significant inverse association”, if a reduction in risk was
reported with a non-significant trend or non-significant
confidence interval; (3) “no effect”, if there was a non-
significant positive association.
Results
A total of 76 studies that investigated the association between
physical activity and breast cancer risk were identified. Among
these, 72 were conducted in women and four in men. Addi-
tionally, across these studies, there was considerable variation
with regard to the study design, populations, contrast in the
exposure variable (i.e., physical activity), and adjustment for
confounding variables. The study designs included prospective
cohort (n ¼ 28),9e36 retrospective cohort (n ¼ 5),37e41 and case-
control (n ¼ 43).42e84 Physical activity was assessed during
leisure-time,3,9e26,28e31,33e37,39,40,42e47,50,51,53e64,66e74,76e81,
84
transportation,19,38 household,34,38,66,67,76 and in occupa-
tional settings.14,15,17,21,24,27,33,35,38,41,48e52,57,63,64,66,67,69,
71,76,78,81e84
All studies measured physical activity either
using self-report,9e14,16e40,42,47,50,53,59,60,62,64,66e68,75,78,79,81,82
interview-administered,15,41,43e46,51,54e58,61,63,69e73,76,80,83,84
or telephone-administered methods,48,49,74,77 with no studies
using an objective-measure of physical activity and few studies
using reliable and/or valid subjective measures of physical
activity.12,16,18,21,22,30,51,54,66e68
Despite the great variability in study characteristics, results
generally supported a positive link between physical activity
and breast cancer risk. Of the 76 studies reviewed, 40 (53%)
reported a statistically significant protective effect for physical
activity on breast cancer risk10,13,14,16,21,22,30,33e36,38,40e45,
50,54,58e60,63e67,69,71,74e77,79,81e84
; 28 (37%) studies found
a non-significant risk reduction of physical activity on reducing
breast cancer risk9,11,17e19,23e27,31,32,37,39,47e49,51,53,55,57,61,62,
70,72,73,78
; and only eight (10%) studies had no evidence for an
association between physical activity and breast cancer
risk.12,15,20,29,52,56,68,80 Notably, none of the studies reviewed
observed a significant positive (i.e., harmful) association
between physical activity and breast cancer risk. Of the 40 studies
demonstrating a reduction in breast cancer risk, the magnitude of
the decrease was, on average, 36%, with case-control studies
(40%) more frequently observing a reduction in breast cancer risk
compared to cohort studies (31%). When all the studies were
included, the magnitude of decrease was 29%, with again, case
control studies (35%) reporting a greater reduction in breast
cancer risk than cohort studies (21%) (Figs. 1 and 2).
To evaluate whether specific aspects of physical activity
participation influence breast cancer risk, studies have examined
the effect of timing (i.e., current or historic/past activity behavior)
and intensity, including, moderate-intensity13,20e23,34,54,55,63,67,83
and vigorous intensity13,17,18,20e23,28,29,31,34,42,47,51,54,55,58,63,67,
72,76,83
exercise on reductions in breast cancer risk. To investi-
gate the influence of the timing of physical activity on breast
cancer risk, studies have assessed activity behavior in different
periods of the lifespan, such as adolescence,18,20e22,42,47,50,51,
54,56,62,66,68,69e72,74,75,77e80,83
young adulthood,14,18,21,29,42,54,56,
66,68,75,76,78,79 18,20e22,26,42,50,54,66,68,69,76,83
middle-age, and late-
adulthood,18,22,38,42,50,54,66,68,69,76 as well as different time-
intervals prior to breast cancer diagnosis, such as one to two
years prior,13,29,47,51,56,59,70,75,83 10-years prior,10,46,51,53,71 20-
years prior,51 and an average of these time-periods (i.e., life-
time activity behavior).13,16,28,43,45,46,51,54,63,66e68,71,76,83,84
When compared, the effect of physical activity on reducing
breast cancer was stronger for vigorous-intensity physical
activity (26%) than moderate-intensity physical activity (13%),
and assessment of lifetime physical activity (30%) was more
consistently associated with reduced breast cancer risk, compared
to regular participation in physical activity during adolescence
(26%), young-adulthood (11%), middle-age years (12%), and
late-adulthood (23%).
Studies have also examined potential effect modifiers on the
association between physical activity and breast cancer risk. The
most common effect modifiers included menopausal sta-
tus,9,10,17,19,30,31,33,35,42,43,49e51,54e56,58e60,62,63,66,67,71,73,79,81,84
body mass index,9,10,12e14,19,21e24,26,30,31,33e35,49,50,56,59,75,76,
Fig. 1. Strength of association between physical activity and breast cancer risk
among cohort studies.
 P.D. Loprinzi et al. / Journal of Exercise Science & Fitness 10 (2012) 1e7
Fig. 2. Strength of association between physical activity and breast cancer risk
among case-control studies.
83,84
family history of breast cancer,13,23,45,46,59,76,83 and
parity.13,21,23,34,44,49,50,59,74,75,83 When compared, the effect of
physical activity on reducing breast cancer was stronger for
postmenopausal women (30%) than premenopausal women
(26%); participants not overweight (37%) compared to over-
weight participants (19%); women without a history of breast
cancer (21%) compared to women with a family history of breast
cancer (12%); and little difference was found between parous
women (23%) and nulliparous women (25%).
Discussion
Collectively, the epidemiologic literature provides substantial
evidence that regular participation in physical activity can reduce
the risk of breast cancer. To aid in the prevention of breast cancer,
regular participation in physical activity should begin in early
childhood, persist throughout adulthood, and be of at least
moderate-intensity. While it might be concluded that the data are
conclusive, the lesson learned regarding the use of hormone
replacement therapy suggests caution. Hormone replacement
therapy was considered, by many, to decrease convincingly the
risk of heart disease and cognitive function loss based on epide-
miologic data, only to be shown to be associated with increased
risks of heart disease and cognitive dysfunction from the results of
placebo-controlled, double-blind, randomized clinical trials.85,86
Understanding the causal pathway between physical activity and
breast cancer risk could be helpful in the development of physical
activity interventions by providing further information on the
dose, intensity, and frequency of physical activity across various
exercise domains needed to protect against cancer.
Establishing the biological mechanisms that underlie an
association between physical activity and breast cancer risk is
an important next step in developing a body of evidence
linking health behavior to disease outcomes. The proposed
mechanisms by which physical activity exerts a protective
effect against cancer can be broadly divided into the following
categories: (1) decreases in sex hormones; (2) decreases in
adiposity; (3) increases in immune function; and (4) changes
in markers of insulin resistance.87 Some studies support the
concept that physical activity reduces breast cancer risk
through favorable changes in the following biological mech-
anisms/biomarkers: decreased adiposity; decreased available
sex hormones (i.e., lower estrogens and androgens); higher sex
hormone binding globulin (SHBG) levels; decreased
3
metabolic hormones (leptin and adiponectin); reductions in
markers of insulin resistance (i.e., insulin, glucose, C-peptide,
and glycosylated hemoglobin); and reduced inflammatory
markers [i.e., tumor necrosis factor alpha, interleukin-6 (IL-6),
and C-reactive protein].88e91
Sex hormones and adiposity
It is well-established that women with increased exposure
to sex hormones, namely estrogen and progesterone, are at an
increased risk for breast cancer.92,93 Elevated levels of sex
hormones and cumulative exposure to sex hormones stimu-
lates tumor development and growth through mammary cell
proliferation.94 Consequently, women with an early onset of
menarche, regular lifetime ovulatory cycles, and late meno-
pause are at an elevated risk for breast cancer,95 with an
increased risk ranging from 20% to over 400%.96e100
Participation in regular physical activity might reduce
circulating levels of sex hormones, and thus reduce breast
cancer risk, by delaying the onset of menarche in childhood,
and in adulthood, inducing menstrual cycle irregularities, such
as anovulation, oligomenorrhoea and amenorrhea. This
assertion is supported by both observational studies,101e103
and exercise intervention studies.104,105 Importantly, in addi-
tion to the direct influence of physical activity, it is likely that
delaying the onset of menarche and inducing anovulation is
influenced by levels of adiposity. Adipose cells act as
a secondary hormonal gland by secreting estrone and estra-
diol; thus, reduced circulating levels of sex hormones might
require both prolonged exercise and caloric restriction to
minimize adipose cell hypertrophy and proliferation. Future
research is needed to determine if physical activity can affect
sex hormones independent of changes in adiposity.
Immune function
Chronic inflammation has been recognized as a risk factor
for cancer,106 particularly through cellular changes and
oxidative stress associated with inflammation.107 At moderate
levels and intensities, regular participation in physical activity
might help reduce inflammation by decreasing proliferation of
immunological products, such as C-reactive protein,
interleukin-6, macrophages, natural killer cells, lymphokine-
activated killer cells, and lymphocytes.90,108 A randomized
controlled trial in obese non-cancer postmenopausal women
showed that a 6-month weight loss program, comprised of
regular exercise and a hypocaloric diet, significantly decreased
levels of interleukin-6, C-reactive protein, and tumor necrosis
factor-alpha.109 In contrast, there were no changes in these
immunological biomarkers in the diet-only control group.
Additional research is warranted as to whether physical
activity can reduce inflammation in women with breast cancer.
Insulin-related factors
Long-term exposure to elevated levels of insulin has also
been associated with breast cancer risk,110 as well as a two and
4 P.D. Loprinzi et al. / Journal of Exercise Science & Fitness 10 (2012) 1e7
three times higher risk for breast cancer recurrence and breast
cancer death, respectively.111 Specifically, high insulin levels
stimulate the production of insulin-like growth factors (IGFs),
which are associated with increased breast cancer risk through
their stimulatory effect on cell turnover.112 In addition to
specific biomarkers (e.g., IGFs), insulin-resistance is thought to
play an important role in breast cancer development. For
example, in a meta-analysis conducted by Larsson and
colleagues113 a 20% increased breast cancer risk among indi-
viduals with type-2 diabetes was found, though not all studies
have shown such an association.114 Regular participation in
physical activity is positively associated with insulin sensi-
tivity115 and inversely associated with fasting insulin levels116
and IGFs.117 The physical activity-lowering effect on IGFs
might not only inhibit mammary cell turnover, but decreased
IGFs might also reduce the availability of sex hormones through
hepatic synthesis of sex hormone binding globulin.118
Other potential factors
In addition to the potential mechanisms previously dis-
cussed, there are other possible mechanisms that might
mediate the relationship between physical activity and breast
cancer risk. It is conceivable that physical activity could
influence breast cancer risk indirectly through behavioral
practices such as cancer screening; therefore, future studies
investigating the biological mechanisms responsible for the
protective effect of exercise on breast cancer should control
for such behavioral practices, as it is possible that physically
active, health conscious individuals are likely to employ other
practices, such as cancer screening (e.g., mammography), to
help prevent cancer development.
Conclusion
Overall, there is substantial evidence that regular partici-
pation in physical activity can reduce the risk of breast cancer.
The mechanisms responsible for the protective effect of
physical activity on breast cancer risk and recurrence are
likely to be through changes in sex hormone levels, immune
function, adiposity, and insulin-related factors. The epidemi-
ological evidence suggests that to aid in the prevention of
breast cancer, regular participation in physical activity should
begin in early childhood, persist throughout adulthood, and be
of at least moderate-intensity. As recommended by Irwin
et al119 and consistent with current physical activity guide-
lines,120 children and adolescents (6e17 years e both boys
and girls) should engage in at least 1 hour of moderate-
intensity aerobic activity on a daily basis and perform
vigorous-intensity aerobic activity at least 3 days a week.
Additionally, children and adolescents should participate in
muscle and bone strengthening activities at least 3 days
a week. Although it is unknown how much exercise is needed
for maximum reduction in breast cancer risk, a reasonable
approach would be to follow the physical activity guidelines
for all adults. Thus, adult men and women should engage in at
least 150 minutes of moderate-intensity and/or at least 75
minutes of vigorous-intensity physical activity per week.
Additionally, adults should participate in muscle and bone
strengthening at least 2 days a week.
Implications for health care professionals
The convincing evidence for physical activity reducing
breast cancer risk suggests that health care professionals should
encourage their patients to engage in physical activity on
a regular basis. To enhance the patients confidence and moti-
vation to engage in physical activity, health care professionals,
whenever possible, should use evidence-based patient coun-
seling techniques such as Brief Negotiation Interviewing and
Motivational Interviewing.121e123 By adopting these patient-
centered approaches, health care professionals are more likely
to dialogue with their patients about their physical activity
behavior. Notably, brief motivational interviewing by health
care professionals has been shown to be a feasible and poten-
tially effective office-based strategy for promoting physical
activity in children and adults.124
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