Scientists Discover why Aromatase Inhibitors may Cause Arthritis

Scientists and researchers have tracked down the probable cause of the development of severe arthritis for a subset of women taking aromatase inhibitors to treat breast cancer.

Certain genetic variants were discovered by Mayo Clinic researchers and their international colleagues that lead to the condition. The findings will appear in the Journal of Clinical Oncology.

“Many women stop taking aromatase inhibitors due to the accompanying joint pain,” said James Ingle, M.D., Mayo Clinic oncologist and senior author of the study, in a press release. “We used the latest genetic technology in a very large group of women and discovered totally new clues to the cause of the main reason women stop this potentially lifesaving drug. Our findings open the door to finding ways to identify women who will develop these side effects and treat those who do, thus allowing more women to take this therapy and decrease their chances of breast cancer recurrence.”

Postmenopausal women with early stage breast cancer most commonly use aromatase inhibitors as adjuvant therapy. Aromatase inhibitors (AIs) which interfere with the body's ability to produce the hormone estrogen, are rapidly changing the standard of treatment for breast cancer.

The team of researchers included investigators from the United States, Canada, and Japan. The team conducted a genome-wide association study to identify the gene variants, called nucleotide polymorphisms (SNPs). SNPs are associated with musculoskeletal pain.

The subjects were patients that were enrolled in a prospective clinical trial, MA27, comparing two aromatase inhibitor drugs. The trial was conducted by the NCIC Clinical Trials Group in Canada and the NCI-sponsored North American Breast Cancer Groups.

Two controls were matched with each patient. Each patient selected experienced arthritis-like side effects within the first two years of treatment, or had already dropped out of the trial because of the pain. Researchers studied 293 separate cases, comparing them to 585 controls.

The team discovered four likely SNPs on chromosome 14. All of the SNPs were near the gene T-Cell Leukemia 1A, which they discovered also was estrogen dependent. One of the SNPs also created an estrogen response with increased gene expression after exposure to estradiol, a widely used post-menopausal treatment. The results provide researchers with genetic markers for the aromatase inhibitor-induced arthritis and clues to find ways to treat it.

More than 3,700 physicians, scientists and researchers, and 50,100 allied health staff work at Mayo Clinic. The clinic treats more than half a million people each year.