Painkillers Tied to Lower Breast Cancer Risk

Study: Chances reduced in women taking ibuprofen, aspirin

TUESDAY, April 8, 2003 (HealthDayNews) -- Over-the-counter pain relievers may reduce the risk of breast cancer by up to 50 percent in some women.

Women who took two or more regular tablets of aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) developed fewer breast cancers, according to a study published in Proceedings from the 94th annual meeting of the American Association for Cancer Research. (The meeting itself, scheduled to be held in Toronto, was postponed because of an outbreak of severe acute respiratory syndrome.)

"This is the fifteenth study to show this effect," says lead author Dr. Randall Harris, director of the Center for Molecular Epidemiology and Environmental Health at Ohio State University. "We found that the use of NSAIDs reduced the risk of breast cancer significantly."

Some experts, however, feel that the evidence is not quite there yet.

"Studies like this we certainly pay attention to, but they're somewhat imperfect in that patients are not perfectly matched," says Dr. Sheldon Feldman, chief of the Louis Venet Comprehensive Breast Cancer Service at Beth Israel Medical Center in New York City. "It looks promising enough that we would love to see a randomized, prospective, double-blinded trial trying to really prove that this is true." This type of trial is considered the gold standard in science.

Harris's study was an epidemiological one, meaning that he and his colleagues looked at existing data, in this case from the Women's Health Initiative Observational Study, a 15-year, government-sponsored initiative aiming to reduce coronary heart disease, breast and colorectal cancer, and osteoporotic fractures among postmenopausal women.

In all, 80,741 postmenopausal women between the ages of 50 and 79 were included in the analysis. The women had no history of breast cancer or any other type of cancer (except non-melanoma skin cancer). After 43 months, researchers noted 1,392 confirmed cases of breast cancer.

Women who took two or more NSAID tablets each week for five to nine years exhibited a 21 percent reduction in their incidence of breast cancer. Regular NSAID use for 10 or more years was associated with a 28 percent reduction. Regular doses of acetaminophen or low-dose or baby aspirin did not have an effect on the incidence of breast cancer. The standard doses were 325 milligrams of aspirin and 200 mg. of ibuprofen.

"We also looked at individual compounds," Harris says. "Aspirin had a 22 percent reduction with 10 or more years of use, and the most striking was ibuprofen, which produced approximately a 50 percent reduction in the incidence of breast cancer.

"We did adjust for other risk factors and found very good consistency and stability of estimates. The effects were also present in high-risk women," he adds.

The NSAIDs may be inhibiting the cox-2 gene, which is overexpressed in most human breast cancers. "This is the trigger gene of inflammation," Harris explains. "We do have a lot of evidence from molecular studies [that] when we block the cox-2 gene and enzymes, we block many steps in cancer -- mutations, division of cancer cells, angiogenesis, metastasis."

This may explain why acetaminophen, which does not block cox-2, did not appear to cause a reduction in breast cancer risk. Acetaminophen is not a NSAID.

But other mechanisms may be at work, Feldman points out.

"When you look at a study like this, you have to ask if there is anything different about patients who take medications like NSAIDs," he says. "What makes people prone toward having arthritis or aches and pains?"<.p>

More estrogen has been associated with both breast cancer and bone problems.

"It's possible," Feldman adds, "that more of the patients who took the NSAIDs were patients who had bone health issues, and the reason was that their lifetime exposure to estrogen has been lower."

While provocative, the study findings are not a good reason to start taking NSAIDs on a regular basis, especially as they can cause side effects, Feldman says.

Harris, on the other hand, seems more convinced of the drugs' value.

"In my opinion, the evidence is very compelling and converging, suggesting that a woman can reduce her chance of developing breast cancer by regular intake of compounds like aspirin and ibuprofen," he says. "I take 200 mg. ibuprofen daily and I have for more than 10 years, so I would recommend that a woman over 40 might consider taking a standard dose of one of these compounds daily. But if they do, they really need to advise their physicians because of the low frequency of side effects, and they do need to be monitored."

Another group of researchers publishing in the same Proceedings announced that they had identified a new gene, C35, which seems to be linked to breast cancer. Some 65 percent of the breast cancer tissues tested over-expressed this gene. That gene may one day represent a target for new drugs as well as a way to determine who develops more-aggressive-than-usual tumors.

Researchers are also looking forward to developing treatment for breast cancers that involve C35. It likely will need a two-pronged approach, says Dr. Deepak Sahasrabudhe, director of the Hematology-Oncology Fellowship Program at the University of Rochester School of Medicine and Dentistry.

"It may entail an agent targeting C35, together with standard radio- or chemotherapy to induce further tumor cell death. A vaccine therapy to prevent the growth of C35-expressing tumor cells might also be a treatment approach," Sahasrabudhe says.

More information

Read about the Women's Health Initiative at the National Heart, Lung, and Blood Institute. For more on breast cancer, visit the National Cancer Institute or the Susan G. Komen Breast Cancer Foundation.

SOURCES: Randall Harris, M.D., Ph.D., professor, College of Medicine and Public Health, and director, Center for Molecular Epidemiology and Environmental Health, Ohio State University, Columbus; Sheldon Feldman, M.D., chief, Louis Venet Comprehensive Breast Cancer Service, Beth Israel Medical Center, New York City; American Association for Cancer Research press releases
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