Aromatase Inhibitor-Associated Arthralgia May be Influenced by Genetics

Investigators presented new research that reveals a possible genetic basis for why Aromatase inhibitor-associated arthralgia (AIAA) occurs in breast cancer survivors and shows promise for treating the side effect without interfering with the drug’s efficacy.

AIAA produces severe joint pain and as many as 10% of women experiencing AIAA choose to prematurely discontinue their drug treatment as a result.

The research was performed by investigators from the University of Pennsylvania’s Abramson Cancer Center and presented during the 2010 meeting of the American Society of Clinical Oncology.

The team, led by Jun Mao, MD, MSCE, assistant professor of Family Medicine and Community Health, studied individual genetic variations that could potentially influence both the onset and severity of AIAA. The team studied 390 postmenopausal women with stage 0 to III breast cancer. All the women were receiving adjuvant therapy with aromatase inhibitors who reported joint pain related to their drug therapy.

Women carrying at lease one copy of a “7-repeat” genetic variant in the aromatase enzyme (CYP19A1) had a lower chance of developing AAIA than those with at-least one “8-repeat” allele of the same gene. Additionally, 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.

"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," said Angela DeMichele, MD, MSCE, an associate professor of Hematology/Oncology and Epidemiology and Biostatistics, and a co-author on all three of the studies, in a news release. "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."