Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, are used to treat common conditions such as pain and fever and chronic conditions such as arthritis and are given prophylactically to reduce the risk of heart attacks and stroke. Interest has also been growing in using NSAIDs to prevent cancer. Studies have found an inverse association between NSAID use and colorectal cancer, but studies of NSAIDs and breast cancer risk have had mixed results.
To investigate the association between NSAID use and breast cancer risk, Sarah F. Marshall, of the University of Southern California in Los Angeles, and colleagues analyzed data on 114,460 women in the California Teachers Study cohort who were ages 22 to 85 and free of cancer at the baseline of the study, 1995 to 1996. During the follow-up period, 1995 to 2001, 2,391 women were diagnosed with breast cancer of known receptor status.
Regular use (i.e., more than once a week) of NSAIDs was not associated with breast cancer risk. However, long-term daily use of aspirin was associated with an increased risk of ER/PR-negative breast cancer, and long-term daily use of ibuprofen was associated with an increased risk of breast cancer and particularly nonlocalized cancer.
"These observations warrant further exploration because of the public health impact such readily available NSAIDs may have on breast cancer," the authors write. "Additional large-scale prospective epidemiologic studies may help clarify the findings by further examining the long-term effects of aspirin and ibuprofen, especially with regard to ER/PR-negative and nonlocalized breast cancer. A more detailed understanding of the tissue-specific effects of NSAIDs, particularly in the context of the complex biological mechanisms involved in the development of different cancers, is also needed."
jncicancerspectrum.oupjournals/
The study was designed to challenge the longstanding notion that cancer arises when susceptible individuals are exposed to cancer-triggering compounds or events over the span of their lifetime. To test whether estrogen, found in both the environment and in some drugs, could reprogram tissue early, Walker, Cook and their team designed a study using female rats that are genetically predisposed to development of uterine leiomyoma, the same kind of benign fibroid tumors that many women have. Typically, 65 percent of rats carrying this genetic defect develop the tumors as an adult, and a set of these animals were used as a "control" group.
For the experimental group, researchers used another set of genetically susceptible rats and exposed them to DES, which is highly estrogenic, 3-5 days after they were born - a crucial period in the development of their reproductive tract.
They found that by the time they reached adulthood (16 months), virtually all of the rats in the experimental group had developed leiomyoma, and the tumors were larger and more numerous than in the control group. In contrast, none of the DES-exposed rats that lacked the genetic defect developed tumors by 16 months.
"The DNA of DES-exposed animals had been modified by DES in a way that changed how genes responded to estrogen, causing this tissue to be hypersensitive to the effects of this hormone," Walker says.
The researchers theorize that DES had permanently altered the rat's normal response to estrogen, a "reprogramming" of the normal physiological responses to estrogen, which led to cancer when the animal had an inherited genetic defect. In that way, DES had changed the "penetrance," or likelihood of causing cancer, of the faulty tumor suppressor gene.
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