© 2005 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Continuing Outcomes Relevant to Evista: Breast Cancer Incidence in Postmenopausal Osteoporotic Women in a Randomized Trial of Raloxifene
Affiliations of authors: Cancer Institute Medical Group, Santa Monica, CA (SM); University of Pittsburgh, Pittsburgh, PA (JAC); University of California, San Diego, La Jolla, CA (EBC); Institute of Cancer Research, Parkside Oncology Clinic, London, United Kingdom (TJP); Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN (JM, DD, RJS); San Francisco Coordinating Center, California Pacific Medical Center Research Institute and the Department of Epidemiology and Biostatistics at the University of California, San Francisco, CA (SRC)
Correspondence to: Silvana Martino, DO, Cancer Institute Medical Group, 2001 Santa Monica Blvd., Ste. 560W, Santa Monica, CA 90404 (e-mail: smartino{at}cimg.org).
The comments from Dr. Yalcin and colleagues raise a clinically relevant question. Clinical data suggest that the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors, is associated with decreased risks of several cancers, including breast cancer (1–3). That use of COX-2 inhibitors might potentiate the reduction in incidence of invasive breast cancer demonstrated with raloxifene therapy in the Continuing Outcomes Relevant to Evista (CORE) trial (4) is a reasonable hypothesis. The CORE trial protocol did not require investigators to record the subject's use of aspirin or NSAIDs, including the COX-2 inhibitors (rofecoxib, celecoxib, and valdecoxib). However, this information could be voluntarily recorded as a concomitant medication, without specifying dosage, frequency of use, or compliance. During the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, investigators were required to record all concomitant medication use but—as in the CORE trial—dosage, frequency of use, and compliance were not recorded. Because aspirin and the NSAIDs ibuprofen and naproxen are available both as prescription only and nonprescription dosages and are indicated for a variety of conditions (i.e., headache, flu symptoms, general muscle aches or pain), it is reasonable to expect that information relating to use of these agents would be unreliable and thus would confound the results and their clinical interpretation. By contrast, data relating to use of the COX-2 inhibitors may be more reliable because these agents are available only in prescription dosages with more limited indications. The COX-2 inhibitors became clinically available in the United States either while the MORE trial was concluding (rofecoxib and celecoxib) or after it was finished (valdecoxib). Therefore, it is unlikely that use of these agents would have impacted the 72% reduction in incidence of invasive breast cancer observed in the MORE trial after 4 years of raloxifene (5). Regarding the use of COX-2 inhibitors during the CORE trial, of the 4011 women who chose to enroll in the CORE trial, 137 (96 from the raloxifene group and 41 from the placebo group) reported using one of these agents sometime between the end of the MORE trial and the end of the CORE trial. There was no statistically significant difference between the raloxifene and placebo groups in reported use of COX-2 inhibitors (3.5% versus 3.2%, respectively; P = .64). Only two invasive breast cancers were reported in these 137 women, one in each treatment group. In summary, our data do not allow us to answer the interesting question posed by Dr. Yalcin and colleagues.
REFERENCES
(1) Terry MB, Gammons MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA, et al. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 2004;291:2433–40.
(2) Johnson TW, Anderson KE, Lazovich D, Folsom AR. Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer. Cancer Epidemiol Biomarkers Prev 2002;11:1586–91.
(3) Harris RE, Chlebowski RT, Jackson RD, Frid DJ, Ascenseo JL, Anderson G, et al. Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women's Health Initiative. Cancer Res 2003;63:6096–01.
(4) Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mershon J, Disch D, et al. Continuing Outcomes Relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 2004;96:1751–61.
(5) Cauley JA, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie DW, et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Breast Cancer Res Treat 2001;65:125–134.[CrossRef][ISI][Medline]
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J Natl Cancer Inst 2005 97: 542.
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