In a recent study published in the journal Cancer Research, researchers found that overweight or obese postmenopausal women with estrogen receptor (ER)-alpha-positive breast cancer who took nonsteroidal anti-inflammatory drugs (NSAIDs) had a significantly decreased incidence of cancer recurrence.

In the study, researchers identified 440 postmenopausal patients with ER-alpha-positive breast cancer and were classified as normal weight, overweight, or obese. Patients were considered NSAID users if they took aspirin, celecoxib, ibuprofen, meloxicam, naproxen, or another cyclooxygenase (COX)-2 inhibitor.

The researchers found that the patients who took a daily NSAID had a 52% lower breast cancer recurrence rate (P=0.05) and, although not statistically significant, continued to be disease-free for more than 2 years longer than patients who did not take a daily NSAID.1

Continue Reading

Furthermore, the researchers sought to determine the mechanisms that might be behind this effect. They found that obese patients had greater COX-2 expression and prostaglandin E2 (PGE-2) production, which was associated with increased preapidocyte aromatase expression. This effect was inhibited by celecoxib, a COX-2 inhibitor.

They also found that obese patients had increased breast cancer cell ER-alpha activity, growth, and metastasis compared with normal-weight women, but the difference was decreased or completely eliminated by aromatase inhibitors.1

RELATED: Preventing Estrogen Receptor-Negative Breast Cancer: Research Continues

The researchers acknowledge that it is too soon to advise overweight and obese women diagnosed with breast cancer to take daily aspirin or NSAIDs to reduce the risk of recurrence, but suggest that the results warrant future studies to test the combination of aromatase inhibitors and COX-2 inhibitors in obese, postmenopausal women with ER-alpha-positive breast cancer; however, one should question whether a COX-2 inhibitor should be prescribed to an overweight or obese patient at all.

According to the National Heart, Lung, and Blood Institute, being overweight or obese increases a patient’s risk for coronary heart disease and stroke.2 In addition, NSAIDs, particularly celecoxib, are associated with an increased risk for cardiovascular events, including myocardial infarction and stroke.

Semiselective NSAIDs that have an increased affinity for COX-2 over COX-1, such as diclofenac, etolodac, and meloxicam, should be used with caution in patients at increased cardiovascular risk. Nonselective NSAIDs, like ibuprofen and naproxen, have less risk for cardiovascular events, and aspirin, which has a higher affinity for COX-1, is cardioprotective at low doses.3 Therefore, it may not be safe to prescribe an NSAID to an overweight or obese patient already at risk for cardiovascular events.

In the Cancer Research study, about 81% of patients considered NSAID users were taking aspirin, but researchers credit their effect on cancer risk and progression reduction to its COX-2 inhibition.1

RELATED: Regular Aspirin Use Doesn’t Reduce Breast Cancer Risk

Thus, it may be reasonable to recommend aspirin over other NSAIDs to reduce the risk of breast cancer recurrence while maintaining patient safety, but this research warrants future study to determine the efficacy and safety in postmenopausal women with breast cancer.

Ultimately, overweight or obese women have increased COX-2 expression, thereby increasing ER-alpha activity. NSAIDs changed the environment of the women’s bodies to be more similar to that of normal-weight women, resulting in increased susceptibility to aromatase inhibitors.

Future prospective trials should be conducted to assess the effect of NSAIDs on postmenopausal women with breast cancer before clinicians begin to prescribe these medications to reduce the risk of cancer recurrence.

References

  1. Bowers LW, Maximo IX, Brenner AJ, et al. NSAID use reduces breast cancer recurrence in overweight and obese women: role of prostaglandin-aromatase interactions. Cancer Res. 2014;74(16):4446-4457.
  2. National Heart, Lung, and Blood Institute. What are the health risks of overweight and obesity? http://www.nhlbi.nih.gov/health/health-topics/topics/obe/risks.html. Updated July 13, 2012. Accessed September 4, 2014.
  3. Perry LA, Mosler C, Atkins A, Minehart M. Cardiovascular risk associated with NSAIDs and COX-2 inhibitors. US Pharm. 2014;39(3):35-38.

Expert Commentary
Edith Perez, MD

At first glance, one could presume that this study demonstrated that overweight and obese women who regularly used aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit of several proteins, including COX-2 expression, had a significantly lower recurrence rate of hormone receptor-positive breast cancer and even a 28-month delay in time to recurrence compared with those who did not report taking non-NSAID agents.

However, one should be cautious with potential over-interpretation of the results. This was an unplanned retrospective study relying on review of medical records, there was no information related to duration or compliance of NSAID use, and there were very few women with normal body mass index. Overall, this study brings up an issue that has been debated for a long time, and one that deserves a large prospective study.

–Edith A. Perez, MD, Mayo Clinic, CancerTherapyAdvisor.com Editorial Advisory Board Member

Topics:

Breast Cancer