Exercise as it relates to Disease/Can exercise reduce insulin to reduce breast cancer recurrence?

This Wikibooks page is an Analysis of the Journal Article "Randomized Controlled Trial of Aerobic Exercise on Insulin and Insulin-like Growth Factors in Breast Cancer Survivors: The Yale Exercise and Survivorship Study" by Irwin, M. L. (2009).

What is the background to this research?

Breast Cancer has had a tremendous impact on the lives of many women and families from all walks of life. The World Health Organisation (WHO) states that breast cancer is the most common cancer in the developed and developing world. Early detection to improve Breast Cancer outcome and survival remains the cornerstone of Breast Cancer control. It is believed that in 2012 that nearly 1.7 million new cases of breast cancer were diagnosed, which accounts for about 25% of all new cancers in women. Breast Cancer is hormone related which means that particular factors that modify this risk between pre and post-menopausal women will differ substantially.

Age-standardised death rates from Breast cancer by country (per 100,000 inhabitants). Canuckguy et al (2004).

no data      less than 2      2-4      4-6      6-8      8-10      10-12

12-14      14-16      16-18      18-20      20-22      more than 22

This Particular study focuses on post-menopausal Breast Cancer survivors. The average age between these women is 50-60. During this time of life it may become increasingly difficult to maintain a general routine when it comes to fitness and lifestyle. Weight becomes harder to control and bone density decreases due to the lack of estrogen being produced. To compound these issues, many women also suffer from psychological hardships such as depression, anxiety and a general feeling of worthlessness.

The study by Irwin (2009) places emphasis on exercise as a lifestyle intervention in order to decrease high levels of insulin in Breast Cancer survivors. Many studies have revealed that high insulin and insulin-like growth factor-I (IGF-I) levels may be associated with an increased breast cancer risk and/or death. This is strongly associated with obesity and low levels of physical activity, both adverse prognostic factors in women diagnosed with Breast Cancer. Although the mechanisms linking aerobic exercise to breast cancer prognosis are still not fully understood, insulin could prove the link between low levels of physical activity and poor breast cancer prognosis. It is believed that a lowering of insulin levels by 25% may improve survival by 5%.

Where Is This Research From?

This research was conducted by Irwin, M. L. and her colleagues from the American Association for Cancer research. All study procedures were reviewed and approved by the Yale University School of Medicine Human Investigation Committee and their analysis conducted at the Yale-New Haven Hospital Tumour Registry.

What Kind of Research was this?

This study is an example of a Randomized Control Trial (RCT). This type of research is quantitative in nature. They are the Gold Standard in terms of clinical research because they yield an estimate that is unbiased and consistent. Randomized control trials are sometimes criticized mistakenly for being too generalized. This criticism arises because initial studies tend to develop a treatment or test for patients who only have a single problem being studied. In order to account for heterogeneity among participants, a RCT must be quite large to achieve statistical significance. What many researchers end up with is the central tendencies of a very large number of people, which isn't always representative of an individual.

What Did The Research Involve?

Given the need to distinguish modifiable factors that reduce insulin, IGF-I, and Breast Cancer risk, an investigation was undertaken to measure the effectiveness of a 6 month randomized controlled aerobic exercise intervention against usual care on fasting insulin and its binding protein (IGFBP-3) in Seventy-five postmenopausal breast cancer survivors. Participants were physically inactive and diagnosed 1–10 years ago with Stage 0 to IIIA Breast Cancer and who had completed adjuvant treatment at least six months prior to enrolment. Type 2 diabetics, smokers and women with a previous cancer or second cancer were excluded due to the potential effect of these factors on outcomes of interest. These women were randomly assigned to an exercise (n=37) or usual care (n=38) group. The exercise group participated in 150 minutes per week of moderate intensity aerobic exercise. The usual care group were required to maintain their current physical activity level. A fasting blood sample was obtained by each study participant at the start and after 6 months. Blood levels of insulin and IGF were measured with Enzyme-Linked Immunosorbent Assay (ELISA).

What were the basic results?

Moderate intensity exercise such as brisk walking was associated with decreases in IGF-I and IGFBP-3. On average, exercisers increased their moderate to vigorous activity by 129 minutes per week compared to the usual care participants at only 45 minutes. Statistically significant results occurred over the course of the trial. A 7.1% reduction in insulin levels in the exercise group compared to a 13.6% increase in insulin for the control group resulted in a 20.7% difference between the two groups. IGF-I decreased by 3.4% in the exercise group while usual care experienced a 5.5% increase. Similarly, levels of IGFBP-3 decreased by 4.6% in the intervention group versus a 3.3% increase in the control.

What conclusions can we take from this research?

Moderate aerobic exercise in post-menopausal Breast Cancer survivors appears to be associated with a statistically significant decrease in insulin levels. An important discovery in the study was the decrease in IGFBP-3. Comparison to existing literature is problematic due to the inconsistent results of previous studies. Although some studies have directly evaluated Breast Cancer prognosis, a study by Goodwin and colleagues discovered that high levels of IGFBP-3 predicted distant recurrence of breast cancer in postmenopausal women. Tissue analysis of this binding protein revealed an association with poor prognosis. These results conflict with earlier studies that report an increase in IGFBP-3 are linked to a decreased breast cancer risk. Future studies need to examine the relationship among exercise, IGFBP-3 and breast cancer outcomes.

Practical advice

The trial was not appropriately powered to observe the effects of exercise on insulin and IGFs stratified by weight/body fat change. Future studies need to address this critical question as to whether exercise has independent effects on insulin and IGFs or is mediated by changes in body fat. The responsiveness of insulin and IGFs to lifestyle changes is key for improving prognosis. Repetition of this trial with a larger sampling size is necessary to confirm the changes in insulin levels. Such a trial would determine whether exercise has clinically significant effects on insulin and other biological mechanisms that may facilitate the correlation between physical activity and Breast Cancer survival.

Further information/resources

1. What is Breast Cancer? http://www.breastcancer.org/symptoms/understand_bc/what_is_bc
2. Breast Cancer Care. Exercise: http://eprints.bournemouth.ac.uk/20850/1/Exercise%20breast%20cancer%20care%20forum%202012.pdf
3. Insulin Breast Cancer Connection: Confirmatory Data Set the Stage for Better Care: http://jco.ascopubs.org/content/29/1/7.full
4. Menopause and Cancer Risk: http://www.cancer.net/navigating-cancer-care/prevention-and-healthy-living/menopause-and-cancer-risk