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Breast Cancer Prevention through Physical Activity

Katie Collins

November 10, 2008

 

  

 

Introduction

 

            Breast cancer is an immense problem for our nation with over 2.5 million women living today who are currently undergoing or who have previously undergone treatment.  The American Cancer Society estimates that in the year 2008 182,460 new cases of invasive breast cancer will be diagnosed, and 40,480 women will die from breast cancer in the United States.  Even though these numbers seem large, each person may believe that it would never happen to her or someone close her.  However, a woman's risk of developing invasive breast cancer at some point in her life is about 12%.  That means if you track a group of 8 women over the course of their lives, statistics show that one of them will develop breast cancer.  These numbers are extremely frightening and make a woman wonder, is there anything I can do to lower my risk of developing breast cancer?  In the media and medical information, one popular idea has been that exercise can reduce a woman's chance of getting breast cancer.  How much exercise does it require to make an impact and how does exercise affect biological mechanisms of breast cancer?     

Information From the Web

 

In the popular media and all over the World Wide Web, there are many resources that say that women can reduce their risk of breast cancer through exercise.  However, each website will give different information and recommendations.  Listed below are a few sources from well-known organizations that all provide evidence in favor of physical activity providing some risk reduction.  However, each group has their own suggestions about how much exercise is necessary and the possible mechanisms at work.

 

American Cancer Society

http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What_are_the_risk_factors_for_breast_cancer_5.asp?rnav=cri

The American Cancer Society lists lack of physical exercise as a risk factor for breast cancer, and says that increasing physical activity could reduce risk of breast cancer.  The American Cancer Society recommends spending 45 to 60 minutes of physical activity at least 5 days a week.

 

Susan G. Komen

http://cms.komen.org/komen/AboutBreastCancer/RiskFactorsPrevention/AbcLackofExercise?ssSourceNodeId=290&ssSourceSiteId=Komen

Susan G. Komen says that women who do not regularly exercise high a higher chance of having breast cancer.  Regular exercise helps to maintain a healthy weight, decrease total estrogen exposure, and enhance the immune system's ability to kill cancer cells.  The website says that regular physical activity reduces breast cancer risk about 20%.

 

National Cancer Institute

http://www.cancer.gov/cancertopics/pdq/prevention/breast/Patient/page3

The National Cancer Institute says that 4 hours or more of exercise each week should lower hormone levels and decrease breast cancer risk.  They say that this effect of exercise may be of the greatest benefit to premenopausal women of low or normal body weight. 

 

BreastCancer.org

http://www.breastcancer.org/risk/new_research/20070221b.jsp

BreastCancer.org cites a study where researchers found that women needed to do six hours of strenuous exercise to reduce risk of breast cancer and that women with a family history of breast cancer did not see risk reduction from exercise.  However, it appears as though this study did not have a large group of women with early stage breast cancer and does not report measures such as Body Mass Index (BMI).

 

                                         

 

Information from Medical Literature:  Does Physical Activity Reduce Breast Cancer Risk?

 

            The media and websites reference the many studies that have shown the benefits of exercise in reducing breast cancer risks, but what do these scientific studies actually say?  There have been many different research studies examining the association between physical activity and breast cancer risk reduction, but there has been mixed evidence and little understanding behind the exact mechanisms of the phenomenon.  To understand the results of the research studies, we must critically examine the methods and experimental design.

 

Nurse’s Health Initiative Prospective Study Reports Risk Reduction Due to Physical Activity

 

            Rockhill et al. (1999) analyzed data from the Nurse's Health Initiative Study, a prospective study of 701 female nurses ages 30 to 55.  Over a period of 16 years, the women were followed and asked questions about activity levels, breast cancer diagnosis, and other variables such as BMI, smoking habits, etc.  The results showed that women who did on average 7 or more hours of moderate or vigorous activity per week had a 20% lower risk of being diagnosed with breast cancer than women who did less than 1 hour per week of such activity.  However, the study did not show differences between premenopausal and postmenopausal women or different BMI groups.  Also, the study did not show that vigorous activity was more likely to reduce breast cancer risk than less strenuous activity; many of the women who received benefit had participated in walking.  This study did a good job of looking at a large group of women and following them over many years.  However, this study has some weaknesses because it did not ask questions about past activity or estimate lifelong activity.  The study also only used hours per week as a measure of activity instead of calculating metabolic equivalent units (METs) that are used in many other studies.  Despite the few flaws, the study does provide some evidence that physical activity does contribute to a reduced risk on breast cancer.

 

 

Case-Control Study of Lifetime Physical Activity In Women Aged 20-54 Shows Breast Cancer Risk Reduction with Increased Activity

 

            Verloop, Rookus, Van der Kooy, and Van Leeuwen (2000) contributed information to the field with a case-control study that looked at lifetime physical activity in women aged 20 to 54 years.  In a group of 918 women with breast cancer and 918 matched controls, information was collected on lifetime physical activity, job history, physical activity during certain age points (10-12 and 13-15 years old), recent activity levels, and other risk factors such as BMI, reproductive history, etc.  Looking at the lifetime physical activity, active women showed a 30% risk reduction compared to women who were not active.  Women who were active both occupationally and recreationally showed a 39% reduction in risk.  Also, women who had a family history of breast cancer showed a stronger association with physical activity compared to those without family history.  Women with BMI less than 21.8 benefited more from physical activity than those with a BMI over 24.5.  Overall, the study suggests that the most important measurement is lifetime activity level; neither early physical activity (before age 20) or recent activity (last 5 years) was associated with a larger risk reduction than the lifetime activity measurement.  Also, the study did not show an increased risk reduction from increasing the frequency, duration, or intensity of activity.  This study did a good job of looking at a very large group of women who were well matched.  The study also accounted for many different kinds of activity such as occupational and lifetime activity.  Also, by only focusing on premenopausal women, the study looked a more homogenous population to compare.  As with other case control studies, there may have been selection bias and a question if the study population were representative of the general population.

 

Prospective Cohort Study of Postmenopausal Women Ages 50-79 Exhibits Lower Breast Cancer Risk with Increased Physical Activity

 

             McTiernan et al. (2003) conducted a prospective cohort study of 74,717 postmenopausal women ages 50-79 years.  The women gave medical histories and were followed up at 1, 2, 4, 5, and 6 year time points.  In the medical histories, clinical data such as height and weight were measured, history taken of other risk factors of breast cancer, and a history of physical activity and diet.  Women were asked if they did strenuous activity at least three times a week at ages 18, 35 and 50 years.  Women also responded how often they currently walked including the speed, duration, and frequency.  Next women answered how many days a week and the amount of time that they exercised at strenuous levels.  The results showed that women who did strenuous activity at least three times per week at age 35 had a 14% decreased risk of breast cancer compared to less active women, but women who reported that same amount of exercise at age 50 did not show any difference in risk as compared to less active women.  Women who currently exercised for at least 1.5-2.5 hours per week of brisk walking or equivalent exercise (5.1 to 10.0 MET) showed an 18% lower risk of breast cancer than women who were not currently active.  Women who participated in more strenuous activity only showed a slight benefit compared to the modest exercise group with the more exercise group having a 21-22% risk reduction compared to sedentary women.  The study also showed that the group of women who gained the most risk reduction were the women with the lowest BMIs.  For women with a BMI less than 24.13, 5.1-10 MET per week had a 30% risk reduction and women who did 20.1-40.0 MET per week ( 5-10 hours per week of brisk walking) showed a 32% risk reduction.  This was a good study of an extremely large population of postmenopausal women.  The study would have been better if it could have continued longer and have taken more measurements of life long activity levels.     

Case-Control Study of Women Aged 35-75 Demonstrates Exercise Levels Lower Chances of Breast Cancer in Postmenopausal Women 

 

            Kruk (2006) used a case-control design to study 250 women with breast cancer and 301 control women, aged 35-75.  Questionnaires were used to measure lifetime physical activity and involved questions about type, duration, frequency, and intensity of the physical activity including both traditional exercise as well as occupational and household chores.  Specific time intervals were considered: ages 14-20, 21-34, 35-50, and after 50.  The study also collected data on other breast cancer risk factors as well as other variables such as BMI, education, place of residence, etc.  The results of this study showed that in the group of premenopausal women, the level of physical activity was not significantly associated with reduced risk of breast cancer.  However, the most active postmenopausal women showed a 58% reduction in breast cancer risk.  This study shows by far one of the greatest risk reductions seen so far, but the paper is not as clear in presenting how much activity was required to achieve that great amount of risk reduction.  Also, the sample size is much lower than the previous studies, which makes this data questionable, especially since it is reporting values much different from the other studies.  Despite this fact, the study does still support the idea that physical activity does reduce the risk of breast cancer, at least for postmenopausal women. 

 

Information from the Scientific Literature:  What is the biological mechanism of the protective factor of physical activity?

 

            After determining that there is a link between physical activity and a reduced risk of breast cancer, we are left with the larger question of why is this the case.  Many scientists have postulated theories about exercise positively impacting areas that contribute to breast cancer risk such as hormone levels, effectiveness of the immune system, body weight, body fat distribution, and insulin-like growth factors.  However, before we can come to a conclusion about these, we must examine the empirical research that has tested some of these theories.   

 

Relationship Between Physical Activity and Blood Levels of Sex Hormones and Insulin-like Growth Factors

 

            First, Tworoger et al. (2007) did a very careful study examining how levels of various sex hormones and insulin-like growth factors were effected by exercise.  In a group of 565 women ages 33-52 years, timed blood samples were taken at various stages of a woman's menstrual cycle.  Women were also asked about the average amount of time spent each week doing certain physical activities and each woman kept four seven day physical activity diaries.  From these measures, a total MET per week could be calculated.  After comparing the physical activity and the biological levels, there were very few associations found.  The main hormone that showed changes with physical activity was luteal estrogen, which was somewhat decreased with increasing activity.  However, previous studies have not linked luteal estrogen levels with breast cancer risk.  Overall, this study suggests that the breast cancer risk reduction due to exercise is not caused by hormone or growth factor mechanisms.  This study was extremely controlled in terms of timing of sample collection and had a large sample size.  However, the cross-sectional design of the study did not allow for causal relationships to be determined and single blood samples may not have given an accurate picture of average hormone levels.     

 

 

An Animal Model of Breast Cancer Shows that Exercise Manipulation Decreases Breast Cancer Risk

 

            Wang et al. (2008) took the question a step further with an experimental manipulation in an animal model to directly address the question.  This study looked at how exercise at puberty effects expression of BRCA1 gene (a mutation here increases chances of breast cancer) and two other tumor suppressor genes.  The study involved dividing rat pups into three groups at puberty: those exposed to voluntary exercise on a treadmill, sham-exercise control, and non-manipulated control.  After training, the mammary glands of the exercise group had fewer terminal end buds, which correspond to terminal ductal lobular units in humans (the area from which many malignant tumors arise).  At the gene and protein level, exercise reduced ER-alpha and increased ER-beta expression that could have contributed to the change in the terminal end buds.  Also, in the mammary glands of the rats once they had reached adulthood, there were elevated levels of BRCA1 and p53 expression, genes that reduce the risk of breast cancer when they are up regulated.  This study is extremely promising for women who have inherited a mutated form of the BRCA1 gene because their genes may no longer dictate their fate.  There is a possibility that physical activity early and throughout life can reduce a woman's risk of cancer or at least lengthen the time before she develops the disease.  This study's multiple control groups were a positive aspect; however, as with many animal studies we have to question if these results would happen the same way in a human population.

Physical Activity Impacts Biological Mechanisms that Contribute to the Causes Breast Cancer

 

            Finally, Coyle (2008) reviewed the current literature about the mechanisms for physical activity reducing the risk of breast cancer.  His first main finding was that animal studies have shown that physical activity alters cellular mechanisms dealing with cellular proliferation and apoptosis (programmed cell death) in such ways to decrease tumor growth.  Also, human studies have shown that exercise leads to changes in estrogen metabolism that cause reduced epithelial cell proliferation and therefore less cells growing uncontrollably.  Finally, continual physical activity seems to reduce the promoter hypermethylation of tumor suppressing genes, so that the genes are able to remain active and prevent tumors from growing.  This article reviewed a large body of literature a provided a very comprehensive view of the current knowledge about the mechanisms of breast cancer risk reduction due to exercise.

                                 

 

Conclusion:  Physical Activity:  a preventable risk factor?

 

            Even though all of the scientific data do agree on the specific numbers, the current evidence strongly suggests that physical activity does indeed reduce a woman's chance of developing breast cancer.  It appears as though women who are more active have about a 20-30% decreased chance of developing breast cancer.  Another very important and replicated finding is that women with lower BMIs have the most benefit from activity in reducing their breast cancer risks.  This means that women must combine physical activity with proper nutrition to achieve healthy a healthy BMI in order to achieve the best risk reduction.  The question about how much exercise is needed to create benefits of lower breast cancer risks has the most scattered results, but it seems as though a woman should try to do as much physical activity as she is able to do and to continually work towards building up her activity level.  For example, daily hour long brisk walks around the neighborhood are a relatively simple way for women to increase their current activity levels.  Women should also encourage their daughters to participate in physical activities because there may be additional benefits from exercising during childhood and adolescence.  Physical activity could also be extremely important to high risk groups such as women with a family history or those suffering from BRCA1 a gene mutation.  Current research suggests that our daily lifestyle choices such as exercise could impact internal biological processes and affect  our genetic predispositions.  However, no amount of risk prevention factors can substitute for early detection and treatment such as frequent breast self exams, mammograms, and regular visits with health care providers.  Overall, physical activity extremely beneficial to health, and hopefully the message about the breast cancer risk reduction will encourage more people to incorporate physical fitness into their daily lives.

              

This project is dedicated to the memory of my mother Linda Durden Collins,

and the many other individuals and families who have suffered from this devastating illness.

References

Coyle, Y.M. (2008). Physical activity as a negative modulator of estrogen-induced breast cancer.  Cancer Causes Control.  June 10, 2008. [Epub ahead of print]

 

Kruk, J.  (2006).  Lifetime physical activity and the risk of breast cancer: A case-control study.  Cancer Detection and Prevention31, 18-28.

McTiernan A., Kooperberg C., White E., Wilcox, E., Coates, R., Adams-Campbell, L.L., Woods, N., Ockene, J.  (2003).  Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women's Health Initiative Cohort Study. JAMA. 290, 1331-1336.

Rockhill B., Willett, W.C., Hunter, D.J., Hunter, D.J., Manson, J.E., Hankinson. S.E., Colditz, G.A. (1999).  A prospective study of recreational physical activity and breast cancer risk. Arch Intern Med, 159(19), 2290-2296.

 

Tworoger. S.S., Missmer. S.A., Eliassen, A.H, Barbieri, R.L., Dowsett, M., Hankinson, S.E.  (2007).  Physical activity and inactivity in relation to sex hormone, prolactin, and insulin-like growth factor concentrations in premenopausal women.  Cancer Causes Control.  18, 743-752.

 

Verloop, J., Rookus, M.A., Van der Kooy, K., Van Leeuwen, F.E.  (2000).  Physical Activity and Breast Cancer Risk in Women Aged 20-54 Years.  Journal of the National Cancer Institute.  92(2), 128-135

 

Wang, M., Yu, B., Westerlind, K., Strange, R., Khan, G., Pati,l D., Boeneman, K.,
Hilakivi-Clarke, L. (2008).  Prepubertal physical activity up-regulates estrogen receptor beta, BRCA1 and p53 mRNA expression in the rat mammary gland.  Breast Cancer Res Treat. May 31, 2008.  [Epub ahead of print].
 
 

 

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