ASPIRIN INCREASES BREAST CANCER SURVIVLA

February 17, 2010 — The regular use of aspirin might increase survival in breast cancer, according to data published online February 16 in the Journal of Clinical Oncology. Aspirin use was associated with a decreased risk for distant recurrence, breast cancer death, and death from any cause.

Depending on the number of days of aspirin use per week, patients were able to reduce the risk for distant metastasis by 43% to 60%. Likewise, compared with nonusers, aspirin use was associated with a 64% to 71% reduction in the risk for breast cancer-related mortality.

"It is important to realize that this is an observational study, and in such a study we cannot prove that aspirin causes improved survival," said lead author Michelle D. Holmes, MD, DrPH, assistant professor of medicine at Harvard Medical School in Boston, Massachusetts. "It will be important to see if our results can be repeated in other observational studies."

It will also be important, Dr. Holmes told Medscape Oncology, to undertake studies to determine how aspirin might improve survival.

She also emphasized that all women in this study had undergone conventional breast cancer treatment, including surgery, radiation, chemotherapy, and hormonal therapy. "The aspirin they took was not a substitute for these therapies, it was on top of these therapies," she said. "It is also important to understand that aspirin intake can have detrimental side effects, such as gastrointestinal bleeding."

To prove that aspirin can improve survival in women with breast cancer and to ultimately change clinical practice would require a clinical trial, Dr. Holmes added. "However, women with breast cancer who are already advised by their doctors to take aspirin for another reason might take comfort in the fact that the aspirin might also be preventing recurrence of their breast cancer."

Previous Studies Inconclusive

Experimental studies have shown that aspirin can inhibit growth and decrease the invasiveness of breast cancer cells, reduce cytokines involved in bony metastasis, and stimulate immune responsiveness, the authors write. In addition, meta-analyses of aspirin or other nonsteroidal anti-inflammatory drugs have shown a 9% to 30% reduced risk for breast cancer incidence associated with their use. However, the authors note that the association between aspirin use and breast cancer incidence remains inconclusive.

In the current study, the authors hypothesized that aspirin use after a diagnosis of breast cancer would be associated with both a lower risk for breast-cancer-related death and distant recurrence among women with stage I to III disease.

They conducted a prospective observational study involving 4164 female participants in the Nurses' Health Study (NHS) who were diagnosed with stages I, II, or III breast cancer between 1976 and 2002. The women were observed until June 2006 or their death, whichever came first.

Within this cohort, there were 341 breast-cancer-related deaths, 400 distant recurrences (including the 341 breast cancer deaths), and 732 deaths from other causes. A total of 2910 women diagnosed with breast cancer did not provide an aspirin assessment after their diagnosis.

The primary outcome was breast cancer mortality risk according to the number of days per week of aspirin use (0, 1, 2 to 5, or 6 or 7 days), which were assessed at least 12 months after their diagnosis and then updated accordingly.

We measured their aspirin intake after their breast cancer diagnosis, being careful not to assess their aspirin intake in the first year after their diagnosis when they might have been getting radiation and chemotherapy, when patients are advised not to take aspirin," said Dr. Holmes.

Their results showed that aspirin use was associated with a decreased risk for breast cancer death, and the results did not appreciably differ when they were stratified by disease stage, body-mass index, menopausal status, or estrogen-receptor status. The results were all the "more notable" because the NHS failed to find an association between aspirin use and breast cancer incidence, say the authors.

Compared with never users, the multivariate adjusted relative risks (RRs) for breast cancer mortality were:

• 0.88 (95% confidence interval [CI], 0.64 - 1.22) for past use
• 1.07 (95% CI, 0.70 - 1.63) for current use 1 day per week
• 0.29 (95% CI, 0.16- 0.52), for current use 2 to 5 days per week
• 0.36 (95% CI, 0.24 - 0.54) for current use 6 or 7 days per week.

The results were similar for distant recurrence; adjusted RRs were 0.91 (95% CI, 0.62 - 1.33), 0.40 (95% CI, 0.24 - 0.65), and 0.57 (95% CI, 0.39 - 0.82) for 1, 2 to 5, and 6 or 7 days of aspirin use, respectively.

In addition, aspirin use was associated with a decreased risk for mortality from any cause; multivariate RRs for overall mortality were 0.96 (95% CI, 0.76 - 1.21), 0.94 (95% CI, 0.67 - 1.32), 0.53 (95% CI, 0.37 - 0.76), and 0.54 (95% CI, 0.41- 0.70) for past, current 1 day per week, current 2 to 5 days per week, and current 6 or 7 days per week of use, respectively.

For all-cause mortality, the authors note that the protective effect associated with aspirin appears to be "driven by the impact on breast cancer death."

They speculate that the association between breast cancer death and aspirin use was stronger than with recurrence, "because recurrence is more likely to be misclassified than death." There was also a "modest association" with the duration of aspirin use, and the authors note that aspirin use "may influence proximal rather than distal events in the cancer pathway."

"If confirmed, our results may broaden the scope of interventions available to reduce breast-cancer-related morbidity and mortality," they conclude.

The study was supported by a grant from the National Institutes of Health. The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online February 16, 2010.