NSAID Use May Reduce Breast Cancer Recurrence in Obese

Alexander M. Castellino, PhD

August 14, 2014

For postmenopausal women with estrogen-receptor-positive breast cancer who are receiving hormone therapy and who are overweight or obese, the risk for disease recurrence is significantly lower if they also take nonsteroidal anti-inflammatory drug (NSAIDs), such as aspirin, on a daily basis, new research shows.

In addition, these women remain cancer-free for a longer period of time.

The results come from a retrospective review published in the August 15 issue of Cancer Research.

In fact, the risk for breast cancer recurrence was 52% lower in overweight and obese women who took NSAIDs than in those who did not. Mean disease-free survival was also longer in the women who took NSAIDs (78.5 vs 50.6 months).

"These results suggest that NSAIDs may improve response to hormone therapy, thereby allowing more women to remain on hormone therapy rather than needing to change to chemotherapy and deal with the associated side effects and complications," said Linda A. deGraffenried, PhD, associate professor of nutritional sciences at The University of Texas in Austin, in a statement.

She added, however, these results are preliminary and patients should never undertake any treatment without consulting with their physician.

Although previous research has shown a modest risk reduction with NSAIDs (J Clin Oncol. 2010;28:1467-1472), it "did not concentrate on overweight and obese patients," Dr. deGraffenried told Medscape Medical News.

Obesity is typically considered a comorbidity in cancer patients, but in this study, it was considered a different disease. "If we can identify a mechanism by which obesity promotes the worse outcomes associated with more aggressive cancer, we may be able to address approaches that will improve outcomes for these patients," she explained.

Retrospective Study Analyzed Medical Records

The researchers retrospectively analyzed the medical records of patients treated at the Cancer Therapy and Research Center at The University of Texas Health Science Center and the START Center for Cancer Care, both in San Antonio. Of the 440 women in the study cohort, 159 used NSAIDs and 281 did not.

In the study cohort, 58.5% of the women were obese (BMI, >30 mg/m²) and 25.8% were overweight (BMI, 25.0 - 29.9 kg/m²). Average body mass index (BMI) was around 31 kg/m².

In the NSAID group, 81% of the women took aspirin; the rest took ibuprofen, celecoxib, naproxen, meloxicam, or another COX-2 inhibitor.

Because of the small number of women, those with a BMI of 25 kg/m² or higher were pooled for the analysis. For recurrence of breast cancer of any kind (local, contralateral, distal, or metastasis), the odds ratio was 0.48 (95% confidence interval, 0.22 - 0.98; P < .05).

The reduction in risk for recurrence of approximate 50% held when factors such as the use of statins and omega-3 fatty acid — both anti-inflammatory agents — was considered

Obesity Cancer Patients "Facing a Different Disease"

"Overweight or obese women diagnosed with breast cancer are facing a worse prognosis than normal-weight women," Dr. deGraffenried said in a statement. "We believe that obese women are facing a different disease. There are changes at the molecular level. We seek to modulate the disease-promoting effects of obesity."

To explore this issue, the researchers conducted cell-culture experiments. They created a tumor environment with cancer cells, fat cells, and immune cells (which promote inflammation), and showed that the expression of several inflammatory molecules — such as COX-2, prostaglandin E₂, arachidonic acid, and aromatase — increased in obese patients.

However, when NSAIDs were added to the cell culture, levels of these inflammatory molecules decreased.

This study indicates that inflammation is a significant mechanistic component of breast cancer in overweight and obese women. This inflammation might make aromatase inhibitors less effective in preventing recurrence in these patients.

Dr. deGraffenried emphasized that, although exciting, these are preliminary observations from a retrospective analysis that need confirmation. Prospective studies to determine the efficacy of adding NSAIDs to hormone therapy will be initiated in 2015, she reported.

"There are several potential benefits of NSAIDs for overweight and obese women with cancer. It is an intervention that is well tolerated, has minimal side effects, and is inexpensive," Dr. deGraffenried told Medscape Medical News.

"NSAIDs are not going to work for all patients. These studies show that the greatest benefit from NSAIDs will be in those with a disease driven by inflammation, not just obesity," she added.

The authors have disclosed no relevant financial relationships.

Cancer Res. 2014 74; 4446-4457. Abstract

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