Overweight and obese women with estrogen receptor (ER)-positive breast cancer may benefit from daily non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin.
Overweight and obese women with estrogen receptor (ER)-positive breast cancer may benefit from daily non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin. In a retrospective study published in Cancer Research, overweight and obese women who took an NSAID daily had a 52% lower recurrence rate of their breast cancer-even after controlling for statin and omega-3 fatty acid use, both of which are also known anti-inflammatory agents. These patients also had a 28-month delay in the time to recurrence-NSAID users were disease-free for an average of 78.5 months compared with an average of 50.6 months for women who did not use NSAIDs.
With these results, Linda A. deGraffenried, PhD, associate professor of nutritional sciences at the University of Texas at Austin, and colleagues believe that a prospective randomized trial to confirm these preliminary results should now be conducted.
“Our studies suggest that limiting inflammatory signaling may be an effective, less toxic approach to altering the cancer-promoting effects of obesity and improving patient response to hormone therapy,” said deGraffenried in a statement.
Obesity is thought to be a negative prognostic factor for women with postmenopausal hormone-responsive breast cancer, since fat tissue expresses aromatase, an enzyme needed to produce estradiol in the body. Prior studies with the aromatase inhibitors anastrozole and letrozole have shown that these therapies do not work as well in women with a higher body mass index (BMI). A link between higher aromatase production in breast tissue and local inflammation has also been shown.
Based on these observations, deGraffenried and coauthors examined whether breast cancer patients who had a BMI of 25 or more benefited from the anti-inflammatory effects of NSAIDs. The authors included 440 women with ER-positive breast cancer who were treated either at the Cancer Therapy and Research Center at the University of Texas Health Science Center or the START Center for Cancer Care, both in San Antonio. All women were diagnosed between 1987 and 2011. A total of 281 non-users and 159 NSAID users were compared. Eighty-one percent of the NSAID users took aspirin; the others used another NSAID. NSAID users tended to be older (mean age of 60 at diagnosis vs 55 among non-users), postmenopausal, and diabetic.
According to the authors, NSAID use may be a way to boost the response to hormone therapy for overweight women but cautioned that these initial results need to be confirmed in larger prospective trials.
To partly understand the underlying mechanism of NSAIDs on aromatase levels in breast cancer cells, the authors used a laboratory model in which cultured breast cancer cells were incubated in the serum of either normal weight or obese breast cancer patients as a way to mimic the tumor microenvironment, which contains fat and immune cells. The serum from obese patients resulted in the stimulation of two proinflammatory molecules, including cyclooxygenase-2 (COX-2), and resulted in greater preadipocyte aromatase expression.
Both the in vitro experiments and the clinical outcomes suggested that “local estradiol production, induced by macrophage COX-2 activity, may be a key mediator in the link between obesity and postmenopausal hormone-responsive breast cancer progression,” the authors concluded.
The study was funded by the US Department of Defense and the National Cancer Institute.