Medicine News

Aromatase inhibitor-associated arthralgia ( AIAA ) is a major side effect in breast cancer survivors, producing joint pain so severe that as many as 10% 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 has revealed a possible genetic basis for why these side effects occur and shows promise for treating these symptoms without interfering with the drugs' efficacy.

Jun Mao, 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 ). 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 aromatase inhibitor-associated arthralgia 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 aromatase inhibitor-associated arthralgia.

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. There are millions of women receiving aromatase inhibitors, as many as 50% of them experience some level of arthralgia, and up to 10% discontinue their treatment prematurely.

The investigators say that as more breast cancer patients become breast cancer survivors, clinicians must become more knowledgeable about the quality of life issues impacting women after they end active treatment for their cancers. The new findings are key to identifying which women may be at risk of problems like arthralgia.

In a related study, University of Pennsylvania researchers surveyed 300 breast cancer survivors to assess the impact of aromatase inhibitor-associated arthralgia on upper and lower extremity functioning ( Functional disability and aromatase inhibitor-associated arthralgia in breast cancer survivors ) They found that women with aromatase inhibitor-associated arthralgia had greater impairment of both upper and lower extremities than those who did not experience these symptoms. As many as 29% of participants reported that the pain limited their ability to perform their normal activities.

In a third study, Carrie Stricker, led the team of researchers in surveying 490 postmenopausal, non-metastatic breast cancer patients to assess the factors that influenced their stopping aromatase inhibitors therapy prematurely ( Understanding premature discontinuation of aromatase inhibitors therapy in postmenopausal breast cancer survivors ) This is one of only a few studies to analyze the rates at which women discontinue aromatase inhibitor therapy and the variables that predict their decision to do so, and the only designed to evaluate patient-reported reasons for ending aromatase inhibitor treatment. The study found that 7% of the patients studied had discontinued their aromatase inhibitor treatment early, at a mean of 15.7 months from the beginning of treatment. The most significant predictors for stopping therapy were a previous history of taking Tamoxifen, which can also cause arthralgia and other symptoms; having other inflammatory conditions such as arthritis; communication about difficulties with taking aromatase inhibitors, and being married. Patients who stopped aromatase inhibitor treatment early cited side effects as the main reason, with arthralgia being the most common complaint. Effects on bone, hot flashes and cognitive effects were also named as reasons for cessation of therapy. ( Xagena )

Source: University of Pennsylvania School of Medicine, 2010

XagenaMedicine2010