Low Muscle Mass Tied to Death Risk in Early-Stage Breast Cancer

Pam Harrison

April 05, 2018

Sarcopenia, or low levels of skeletal muscle mass, is a highly prevalent though largely unrecognized risk factor for overall mortality in women with stage II and III nonmetastastic breast cancer, an observational study suggests.

Moreover, the degree of muscle and fat mass a woman carries as identified on clinically acquired coomputed tomography (CT) is a more powerful predictor of survival than is body mass index (BMI), the same study indicates.

"In this population of women who have nonmetastatic early-stage breast cancer, we've demonstrated that if they lose weight, they have worse survival and we hypothesized that this was due to muscle loss," Bette Caan, DrPH, senior research scientist, Kaiser Permanente Northern California division of research in Oakland, told Medscape Medical News.

"But we found that sarcopenia is not restricted to patients with metastatic cancer — it is also an underappreciated but significant problem among women with nonmetastatic breast cancer as well, so clinicians can't only worry about adiposity; they should be concerned about a woman's muscle level as it is as important a prognosticator as high adiposity for survival," Caan emphasized.

Clinicians can't only worry about adiposity; they should be concerned about a woman's muscle level. Bette Caan


The study was published online April 5 in JAMA Oncology.

The study included 3241 women aged 18 to 80 years who had been diagnosed with stage II or III nonmetastatic breast cancer at the Kaiser Permanente Northern California or the Dana Farber Cancer Institute in Boston, Massachusetts.

The median age of the patients at the time of diagnosis was 54 years, and the median follow-up was 6 years.

"Muscle area, muscle radiodensity, and adiposity were measured from CT scans within 6 months of diagnosis and before chemotherapy or radiation," the researchers note. As Caan explained, muscle has a higher density on CT scans than does fat, the density of which is normally lower than that of muscle.

Low muscle radiodensity reflects the amount of fatty infiltration into the muscle, which normally shouldn't happen, and this is thought by some to be a surrogate for low muscle quality.

Thus, low skeletal muscle radiodensity represents low skeletal muscle quality, Caan pointed out.

Total adiposity, which was also measured by clinical CT scans, represented the sum of visceral adipose tissue, subcutaneous adipose tissue, and intramuscular adipose tissue each individual patient carried.

At the time of their diagnosis, 34% of the cohort had sarcopenia while 37% had low muscle radiodensity or low muscle quality.

In multivariable analysis, sarcopenia was associated with a 41% (hazard ratio, 1.41; 95% confidence interval, 1.18 - 1.69) greater relative risk for death compared with patients without sarcopenia, the investigators report.

At the same time, patients in the highest tertile of adiposity had a 35% higher relative risk for death compared with patients in the lowest tertile, and this association did not vary significantly by age, BMI, cancer stage, or estrogen receptor status, the researchers add.

The mortality risk was highest among patients with both sarcopenia and high levels of total adiposity, among whom the relative risk for mortality was 89% higher than that in  patients without sarcopenia and with low levels of total adipose tissue.

In contrast, low radiodensity was not significantly associated with survival risk.

Furthermore, an increase in 1 standard deviation of the skeletal muscle index (SMI) was associated with a modest reduction in mortality risk. As Caan explained, the SMI is a way to standardize muscle mass for people of similar heights: the taller the person, the greater the muscle mass required to carry a bigger frame.

Nor, importantly, was BMI related to overall mortality, the researchers point out. For example, the risk for death was similar between patients with normal-weight BMI (18.5 to <25 kg/m2) and those who were overweight (BMI of 25 to <30 kg/m2).  

The risk for death was elevated in obese patients with a BMI of 30 kg/m2 or greater, but not significantly so, the authors point out.

Indeed, only patients in the highest tertile of total adipose tissue but without sarcopenia had a significantly higher risk for death by some 40% compared with those with low total adiposity without sarcopenia.

Conversely, the risk for death was increased regardless of the level of total adiposity among patients with sarcopenia compared with patients with no sarcopenia and low total adiposity levels.

BMI: Not a Good Measure?

As Caan explained, BMI tells clinicians essentially nothing about a patient's body composition.

"You can take an athlete who might have a BMI of 30 kg/m2 but they are all muscle," she said.  "Conversely, you have another person with a BMI of 26 kg/m2 who is totally sedentary and they have lots of fat."

"So just because someone has the same BMI doesn't mean their body composition is the same," she reaffirmed.

For example, Caan showed scans of two patients with an identical BMI of 30 kg/m2, but in one, the SMI was 69 cm2/m2 and the visceral adiposity index was 33 cm2/m2.

In contrast, the SMI in the second individual was only 36 cm2/m2, while the visceral adiposity index was 127 cm2/m2.

"Once we get to a BMI of over 35 kg/m2, the BMI is fairly accurate in identifying women with high adiposity, and typically women with a BMI of over 35 kg/m2 have lower rates of sarcopenia. But it still could be present, so clinicians need to check even these patients for the presence of sarcopenia before putting any patient on a weight-loss diet because if you put a person with low muscle on a weight-loss diet, they are going to lose more muscle," Caan emphasized.

Asked how easy it would be to incorporate clinically acquired CT images into practice, Caan pointed out that many patients with cancer are already being diagnosed with cancer with the use of CT scans.

"There is now software that automates immediately so with a push of the button, you can get this information," she said.

The real challenge is to get this information to oncologists so that they can target patients with the right intervention, Caan suggested.

In the meantime, patients with nonmetastatic early breast cancer in whom sarcopenia is detected or suspected should be advised to start resistance exercise training.

Resistance exercise not only increases muscle strength but also maintains lean body mass and reduces body fat in patients with cancer, Caan pointed out, and can serve as an effective countermeasure to low and low-quality muscle mass.

Researchers also suggest that patients with cancer consume a protein supplement to improve muscle mass.

Fat Mass Gains

Commenting on the study in an editorial, Elisa Bandera, MD, PhD, Rutgers University, New Brunswick, New Jersey, and Esther John, PhD, Stanford University, Fremont, California, point out that changes in body composition often occur after a woman has been diagnosed with breast cancer, especially gains in fat mass relative to lean muscle mass, often because of treatment regimens.

"The novel results in the study by Caan et al further stress the benefits of maintaining and building muscle mass in breast cancer survivors," they state.

Nevertheless, Bandera elaborated that she still believes BMI, while not a perfect measure of adiposity (particularly for normal-weight women), remains a "useful and practical tool" to identify obese women and to make recommendations about weight control, particularly for those with a BMI greater than 35 kg/m2, she noted in an email to Medscape Medical News.

"This new study brings up the issue that when CT scans are available, they could add very valuable information to identify women at particularly increased risk of mortality that may have been missed by just computing BMI — eg, those with sarcopenic obesity — even though these [patients] represented only 6% of participants," Bandera pointed out.

Bandera and John also caution against recommending an intervention such as protein supplementation for patients with cancer because the benefits of this supplementation have not been demonstrated in breast cancer survivors or in an older population.

"Adequate protein intake from healthy food sources is very important at all ages, but particularly for an aging population," Bandera noted. 

"Protein supplementation is different," she added, "and the few studies that have been done in breast cancer survivors did not find any effects on muscle strength or body composition, unlike resistance training, which was shown to improve both," she said, adding that "this is an area that needs further investigation before recommendations can be made."

Caan and the editorialists have disclosed no relevant financial relationships.

JAMA Oncol. Published online April 5, 2018. Abstract, Editorial

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