Mayo Clinic researchers have found that breast cancer survivors taking aromatase inhibitors (AIs) lose significantly less weight when given anti-obesity medications than women with no history of breast cancer or AI use.
The study highlights a “need to develop better approaches to manage and prevent weight gain in patients with a history of breast cancer taking aromatase inhibitors,” said lead researcher Sima Fansa MD, from the Mayo Clinic in Rochester, MN.
Fansa, who presented the findings at ENDO 2023, the Endocrine Society’s annual meeting in Chicago, told Inside Precision Medicine: “This topic is of extreme importance, as a healthy weight has been associated with better breast cancer outcomes by preventing breast cancer recurrence and breast cancer-related mortality. Furthermore, excess weight leads to metabolic complications that increase cardiovascular disease and mortality risks.”
Indeed, cardiovascular disease is currently the most common cause of non-cancer related death in breast cancer survivors.
Fansa added that although dietary and lifestyle changes can benefit these patients, they often do not lead to sustained weight loss, meaning there is a need to consider tools such as anti-obesity medications that not only aid with weight loss but also weight loss maintenance.
The efficacy of anti-obesity medications has been demonstrated in many studies, but has not previously been measured among breast cancer survivors who are often taking endocrine therapies such as AIs. These drugs decrease estrogen synthesis, which can lead to an increase in body fat percentage, a decrease in lean muscle mass, and an overall decrease in metabolism.
The retrospective study included data from 99 women (mean age 63.5 years, mean BMI 34.4 kg/m2) with a history of breast cancer who were using an AI as well as one of three anti-obesity medications: liraglutide, semaglutide, or phentermine.
Their weight loss over 12 months was compared with that of 36 women (mean age 60.4 years, mean BMI 36.3 kg/m2) using one of the same three anti-obesity medications who had no history of breast cancer or AI use.
Fansa reported that women in the AI group had a lower total body weight loss (TBWL)% than those in the no AI group at 3 months (3.7 vs 5.6%), 6 months (3.9 vs 9.5%), and 12 months (5.2 vs 10.5%). The differences at 6 and 12 months were statistically significant.
In addition, significantly fewer women using an AI achieved at least 10% TBWL at 12 months than did those not using an AI, at 22% vs 48.3%.
Despite the suboptimal weight loss response in the AI group, the investigators still observed improvements in fasting plasma glucose (–33.9 mg/dL at 12 months), glycated hemoglobin (–1.1%), and low-density lipoprotein cholesterol (–15.6 mmol/L) levels among these women at 12 months. The same cardiometabolic parameters were also improved in the control group along with blood pressure and non-high-density lipoprotein cholesterol.
Fansa said that as well as decreasing estrogen levels, aromatase inhibitors are associated with fatigue and joint and muscle pain that can limit physical activity, which is another possible reason for reduced weight loss. In addition, AIs are associated with nausea that can be relieved with food intake, while emotional eating due to increased emotional distress associated with their cancer diagnosis could also play a part.
To address the reduced efficacy of anti-obesity medications among AI users, Fansa suggested that there is a need to implement strategies to prevent weight gain. “Health care providers should advise patients on the need to change dietary habits, for example, eating smaller portions, and on the importance of incorporating or increasing physical activity.” This could be done through a multidisciplinary weight management program that includes nutritional and behavioral support.
She added that “health providers need to recognize the negative consequences of weight gain in order to implement weight loss interventions early in the course [of treatment].”
However, “while lifestyle modification is the first and most important step in the treatment of overweight and obesity, health care providers and patients should be aware that weight loss is generally modest and does not lead to sustained weight loss in most patients,” Fansa noted. “As such, we should consider additional tools, such as anti-obesity medications, when appropriate.”
Fansa and team now plan further studies that include larger, more diverse patient populations, all FDA-approved anti-obesity medications, and a control group of breast cancer survivors who are not using any aromatase inhibitors.
“Our ultimate goal is to investigate the mechanisms underlying the decreased weight loss response to anti-obesity medications in patients taking aromatase inhibitors,” Fansa concluded.
