Low Muscle, High Body Fat Affects Breast Cancer Survivorship

There is a strong body of research showing that women with obesity face increased risk of  postmenopausal breast cancer. But the research involving how obesity links to breast cancer survival is still emerging and not as clear.

Now one of the largest studies of its type suggests that having low muscle mass and high amounts of body fat increase the risk of earlier death for women diagnosed with breast cancer. The study offers important insights into how body composition –  beyond obesity and BMI – may affect survival after breast cancer. The study was published in JAMA Oncology. 

“The findings in the paper add new information on the role of body composition on breast cancer survival, says Elisa Bandera, MD, PhD, a professor of epidemiology at Rutgers Cancer Institute of New Jersey who was not involved with the study. “Most studies to date have used body mass index as a measure of adiposity, but this study was able to evaluate muscle mass and total adiposity using computed tomography scans.”

BMI, body fat and muscle
Most human studies involving obesity and breast cancer survival use BMI as the measure given that it is a relatively easy and inexpensive way for researchers to estimate the level of a person's body fat. Yet BMI offers only a general picture: it does not distinguish between how much muscle versus adiposity (body fat) a person has. BMI also does not provide information on the types of fat. Belly or visceral fat, for example, links to greater risk of several diseases, including colorectal cancer.

This may be why research has shown mixed findings when investigating body fat, says Bette Caan, DrPH, Senior Research Scientist at Kaiser Permanente and lead author of the study. “Studies examining effects of BMI have been inconsistent and using only BMI to identify patients at risk may lead to interventions (such as weight loss) that could not benefit patients,” said Cann. “We think more direct measures of components of body composition, using CT scans when available, as they are for many patients, are needed to try and understand exactly what is driving improved or decreased survival.”

Low muscle mass, extreme obesity
For the study, Caan and her colleagues used computed tomography (CT) scans of 3,241 women diagnosed with nonmetastatic breast cancer. The scans, taken when the women were first diagnosed, gave data on sarcopenia (low muscle mass), muscle quality, and body fat.

Surprisingly, slightly over a third of the women had sarcopenia, the loss of skeletal muscle. It was seen across all levels of BMI. Sarcopenia is a degenerative condition that is a natural part of the aging process.

After an average of six years, the study found that women with sarcopenia had a higher risk of mortality compared to those without the condition regardless of body fat. BMI overall was not linked to mortality but survivors having the highest amount of fat tissue showed higher overall mortality compared to those in the lowest category. This was after adjusting for age, tumor type and other factors recognized to affect mortality risk. 

The highest mortality risk was seen for breast cancer survivors with both sarcopenia and high body fat.

Low muscle appears to be as highly prevalent as high adiposity and the prevalence of low muscle is underappreciated in this population, says Caan. There are several possible ways in which muscle may affect survival. Skeletal muscle is the largest organ in the body. “Like adipose tissue, skeletal muscle has a role in regulating whole body metabolism, inflammation, and insulin resistance and is an important prognostic factor in other cancers,” said Caan.

Yet this study provides further support to the view that a dietary pattern replete in red meat, processed meat, refined grains and sugary beverages is associated with a higher risk of colorectal cancer. It also provides support to the theory that diet-related inflammation may partly mediate the link between dietary patterns and colorectal cancer risk.

“Low muscle appears to be as highly prevalent as high adiposity and the prevalence of low muscle is underappreciated in this population, says Caan. There are several possible ways in which muscle may affect survival. Skeletal muscle is the largest organ in the body. “Like adipose tissue, skeletal muscle has a role in regulating whole body metabolism, inflammation, and insulin resistance and is an important prognostic factor in other cancers,” said Caan.

Intentional weight loss while maintaining muscle
A BMI of 30 and over is categorized as obese. In this study the women associated with having the highest amounts of fat tissue – and linked to earlier death – had a BMI over 35. And although BMI overall was not linked to mortality, it still remains an important tool to assist both health providers and the general public, including survivors, in keeping track of a healthy range of body weight, said Bandera.

“We know that BMI is not a perfect measure of adiposity. However, this study found that adiposity increased as BMI went up,” she said. “As this is the first large study evaluating body composition and breast cancer survival, findings need to be replicated in other studies paying attention to impact by hormone subtypes, and potential effects of breast cancer treatment on body composition and survival.”

In an accompanying commentary for the study in the same journal, Bandera, who is also one of the expert panelists on AICR/WCRF's Continuous Update Project reports and the recently released AICR/WCRF Third Expert Report: Diet, Nutrition, Physical Activity, and Cancer: A Global Perspective points out that obesity is highly prevalent among breast cancer survivors.
There are several potential ways that excess body fat may lead to worse outcomes. Fat tissue can produce proteins that cause inflammation and increases blood levels of insulin, estrogen and other hormones that can encourage the growth of cancerous cells. Having excess body fat can affect treatment and lead to diabetes and other harmful conditions.

“In general, when BMI is greater than 30, losing weight most likely will lead to many health benefits including the prevention or better management of most chronic diseases,” said Bandera. “Survivors have different needs and should consult with their health provider for recommendations on weight management tailored to their individual needs based on disease stage and treatment phase”.

Experts also note that that breast cancer survivors who are obese and choose to go on a weight loss program should make sure to incorporate strength training in order to maintain – or build – muscle mass.

Lifestyle and improving survival
The study is observational and does not show cause and effect. Also, there is a chance that sarcopenia could have resulted from the cancer progression rather than be a cause. More research is also needed to help clarify many of the findings.

Caan and her colleagues are working to understand whether effects of adiposity on survival vary by type of adipose tissue, such as whether it is visceral or subcutaneous adipose tissue or both, that contributes to poorer survival.

While research is ongoing, these findings are likely generalizable across many other nonmetastatic cancers because the associations with muscle and improved survival for those with metastatic cancer has been observed across a variety of solid tumors, the paper notes.

AICR recommends that cancer survivors, when they are able, follow the same recommendations as those for prevention, which includes eating a healthy diet and being active daily.

For the latest news and research on how lifestyle habits play a role in survivors health sign up for AICR's Recharge.

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Sources:

Elisa V. Bandera, Esther M. John, Obesity, Body Composition, and Breast Cancer: An Evolving Science. Invited Commentary. JAMA Oncology. April 5, 2018.

Caan BJ, Cespedes Feliciano EM, Prado CM, et al. Association of Muscle and Adiposity Measured by Computed Tomography With Survival in Patients With Nonmetastatic Breast Cancer. JAMA Oncol. Published online April 05, 2018. doi:10.1001/jamaoncol.2018.0137

AICR/WCRF. Diet, nutrition, physical activity and breast cancer survivorship.

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    Published on June 20, 2018

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