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Genetic Differences May Influence the Severity of Joint Pain Among Millions of Women Taking Lifesaving Breast Cancer Drugs

Posted May 27 2010 3:19pm

Aromatase inhibitor-associated arthralgia (AIAA)  is a major side effect in breast cancer survivors, producing joint pain so severe that as many as ten percent of women discontinue their therapy prematurely while undergoing treatment with these lifesaving drugs. New research presented by investigators from the University of Pennsylvania’s Abramson Cancer Center at the 2010 meeting of the American Society of Clinical Oncology reveals a possible genetic basis for why these side effects occur and shows promise for treating these symptoms without interfering with the drugs’ efficacy. Additional research will also be presented shedding light on the physical and psychological factors that influence women’s decisions to stop taking the drugs.

Jun Mao, MD, MSCE, an assistant professor of Family Medicine and Community Health who heads the Abramson Cancer Center’s integrative oncology program, led a team that studied individual genetic variations that could potentially influence both the onset and the severity of AIAA. (“Genetic variation in CYP19A1 and Interleukin-6 and aromatase inhibitor-associated arthralgia in breast cancer survivors,” Abstract #526) His team studied 390 postmenopausal women with stage 0 to III breast cancer receiving adjuvant therapy with aromatase inhibitors who reported joint pain related to their drug therapy.  They found that among this group, women carrying at least one copy of a “7-repeat” genetic variant in the aromatase enzyme (CYP19A1, the target of aromatase inhibitors) had a lower chance of developing AAIA than those with at least one “8-repeat “ allele of the same gene. Having at least one copy of a specific IL-6 haplotype was also correlated with increased pain severity, while the presence of a different variant of that gene was associated with decreased pain.  Both these findings support previous research that indicates an important role for host estrogen metabolism and inflammation in causing AIAA.

“Due to genetic differences, women respond differently to aromatase inhibitors with regard to estrogen levels and inflammatory processes, and as a result, some women are more likely to have this pain or have more severe pain,” says Angela DeMichele, MD, MSCE, an associate professor of Hematology/Oncology and Epidemiology and Biostatistics, and a co-author on all three of the studies. “There are millions of women receiving AIs, as many as 50 percent of them experience some level of arthralgia, and up to 10 percent discontinue their treatment prematurely, so this is a significant issue.”

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