Aspirin and Melanoma Prevention: Data from the Women’s Health Initiative

Abstract & Commentary

By William B. Ershler, MD

Synopsis: In a large population of Caucasian women participating in the Women’s Health Initiative Observational Study, those who used aspirin had a significantly lower risk of melanoma and increased duration of use was associated with incrementally greater protection.

Source: Gamba CA, et al. Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women: The Women’s Health Initiative. Cancer 2013;119:1562-1569.

The incidence of melanoma has been rising1 and in light of marginally effective treatments for advanced disease, early recognition and prevention strategies are increasingly important. Of these, there has been much recent attention for the role of aspirin in the prevention of a broad range of cancers including breast, colon, and gastric.2-4 There is reason to expect aspirin might be beneficial in melanoma prevention as well, in that human melanoma cells over-express cyclooxygenase-2 (COX-2)5 and high COX-2 levels are associated with melanoma progression.6 Indeed, case-control analyses have indicated a protective effect of non-steroidal anti-inflammatory drugs (NSAIDs),7,8 but the results from other analyses have been negative. A randomized trial of alternate-day, low-dose (100 mg) aspirin9 and two additional cohort studies10,11 have failed to demonstrate melanoma prevention for those treated with NSAIDs.

Capitalizing on the well-characterized population participating in the Women’s Health Initiative (WHI) Observational Study, Gamba and colleagues evaluated the association between NSAID use (including aspirin) and cutaneous melanoma risk.

At study entry, use of aspirin and non-aspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50-79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders.

During a median follow-up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used aspirin had a 21% lower risk of melanoma (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.63-0.98) relative to nonusers. Increased duration of aspirin use (< 1 year, 1-4 years, and ≥ 5 years) was associated with an 11% lower risk of melanoma for each categorical increase (P trend = 0.01), and women with ≥ 5 years of use had a 30% lower melanoma risk (HR, 0.70; 95% CI, 0.55-0.94). In contrast, use of non-aspirin NSAIDs and acetaminophen were not associated with melanoma risk.

Commentary

Postmenopausal women who used aspirin had a significantly lower risk of melanoma, and longer duration of aspirin use was associated with greater protection. The observed benefit with aspirin but not NSAIDs is curious and suggests the mechanism of protection might be through pathways other than COX inhibition. However, as the authors point out, women who were using non-aspirin NSAIDS were more likely to have intermittent rather than continuous use. Indeed, the fact that the protective effect increased with duration of aspirin treatment suggests that such might be the case. Still, although large, carefully conducted and analyzed, the study was observational in design and relied on self-report of medication use and sun exposure.

The data, particularly with regard to duration of aspirin use, are reminiscent of what has been observed for aspirin prevention of colon cancer12 and quite possibly other malignancies as well. Randomized, prospective trials are warranted, with a specific focus on those at high risk for melanoma in a manner analgous to those demonstrating colon cancer reduction in patients with Lynch syndrome.12

References

1. Jemal A, et al. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006. J Am Acad Dermatol 2011;65(5 Suppl 1):S17-25.e1-3.

2. Harris RE, et al. Breast cancer and nonsteroidal anti-inflammatory drugs: Prospective results from the Women’s Health Initiative. Cancer Res 2003;63:6096-6101.

3. Rothwell PM, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 2010;376:1741-1750.

4. Tian W, et al. Meta-analysis on the relationship between nonsteroidal anti-inflammatory drug use and gastric cancer. Eur J Cancer Prev 2010;19:288-298.

5. Becker MR, et al. COX-2 expression in malignant melanoma: A novel prognostic marker? Melanoma Res 2009;19:8-16.

6. Kuzbicki L, et al. Expression of cyclooxygenase-2 in benign naevi and during human cutaneous melanoma progression. Melanoma Res 2006;16:29-36.

7. Curiel-Lewandrowski C, et al. Long-term use of nonsteroidal anti-inflammatory drugs decreases the risk of cutaneous melanoma: Results of a United States case-control study. J Invest Dermatol 2011;131:1460-1468.

8. Joosse A, et al. Non-steroidal anti-inflammatory drugs and melanoma risk: Large Dutch population-based case-control study. J Invest Dermatol 2009;129:2620-2627.

9. Cook NR, et al. Low-dose aspirin in the primary prevention of cancer: The Women’s Health Study: A randomized controlled trial. JAMA 2005;294:47-55.

10. Asgari MM, et al. A large cohort study of nonsteroidal anti-inflammatory drug use and melanoma incidence. J Natl Cancer Inst 2008;100:967-971.

11. Jacobs EJ, et al. A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence. J Natl Cancer Inst 2007;99:608-615.

12. Burn J, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: An analysis from the CAPP2 randomised controlled trial. Lancet 2011;378:2081-2087.