Breast Cancer Drugs May Weaken Effects of Weight-Loss Drugs

CHICAGO -- Anti-obesity medications may not work quite as well in women taking certain breast cancer drugs, a researcher reported here.

Among 99 breast cancer survivors, those taking aromatase inhibitors (AI) lost 42% less weight after a year of taking an anti-obesity medication than women not on AIs, said Sima Fansa, MD, of the Mayo Clinic in Rochester, Minnesota.

At 12 months, women not on AIs lost 9.1% of total body weight with anti-obesity medications compared with 5.3% among women on both agents, she explained at ENDO 2023, the annual meeting of the Endocrine Society.

The differences in total body weight loss were apparent as early as 3 months into taking the anti-obesity medications, and were sustained throughout the year.

Women on AIs were less likely to achieve any categorical weight loss after a year on an anti-obesity drug versus women not on one:

• At least 5% of body weight: 49% of women on AIs vs 72% not
• At least 10% of body weight: 22% vs 48%
• At least 15% of body weight: 5% vs 21%

"Up to 27% of women taking aromatase inhibitors for breast cancer treatment gain weight," Fansa pointed out during a press conference, adding that clinicians should warn patients of this possible side effect. She added that cardiovascular disease is the most common cause of non-cancer-related death in breast cancer survivors, with obesity only magnifying this risk.

"Even though breast cancer survivors report high levels of concern about weight after their breast cancer diagnosis, there are significant gaps in the provision of advice or even guidelines on weight gain prevention and weight management," she added.

Breast cancer survivors on AIs did see a few significant changes in metabolic parameters. For example, after a year on an anti-obesity medication, there was an average 33.9 mg/dL drop in fasting glucose, 1.1% drop in HbA1c, and 15.6 mmol/L drop in LDL cholesterol. However, women not on AIs reaped metabolic benefits beyond this, seeing improvements in all three of these measures, plus blood pressure and non-HDL cholesterol.

Fansa's group pinpointed a few factors that were predictive of greater weight loss in breast cancer survivors on these agents. While on an anti-obesity drug, they tended to see greater weight loss if they didn't have type 2 diabetes, were on a higher dosage of their weight loss drug, and if they also engaged in behavioral therapy.

Among the women in the multicenter retrospective study, most were on semaglutide (Wegovy) at 69.8% on AI versus 74.2% not on AI. Those not on semaglutide were either taking liraglutide (Saxenda) (19.1% vs 9.7%, respectively) or phentermine (11.1% vs 16.1%, respectively).

"Semaglutide was actually the best of the three [at inducing weight loss in this population]," Fansa told MedPage Today. "Hopefully future studies will include all FDA-approved medications so that we can have a more comprehensive point-of-view."

Fansa and colleagues also said that "[s]tudies are needed to assess the mechanisms behind the different weight loss response to [anti-obesity medications] in women taking AIs, which we hypothesize may relate to AIs' anti-estrogenic effect on lean and fat mass."

"The more medications that are available, the better it is [for these patients] because we can offer the patients more options so that they can choose what would suit them most in terms of adverse effects, mechanisms of action, and drug intakes," she added when discussing the expectation of new anti-obesity medication approvals on the horizon.

The average age of women in the study was 63, nearly all were white, and the average baseline BMI was 34.5.

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