Adjuvant Letrozole Relieves Rheumatologic Symptoms in Patients with Breast Cancer

Postmenopausal women with hormone receptor-positive (HR+) early breast cancer who stop treatment with adjuvant anastrozole because of grade 2 to 3 arthralgia and/or myalgia (A/M) may benefit from switching to letrozole therapy, new data suggest.

The results are drawn from the Rheumatologic Evaluation of Adjuvant Letrozole in Postmenopausal Women with Breast Cancer (REAL) study, which found that women who experienced grade 2 or higher A/M while receiving anastrozole have fewer rheumatologic symptoms while taking letrozole.

Denise A. Yardley, MD, director of breast cancer research at the Sarah Cannon Research Institute in Nashville, Tennessee, presented results in 261 women who received letrozole therapy after stopping anastrozole therapy due to A/M.

"Adjuvant nonsteroidal aromatase inhibitors (AIs) are the treatment mainstay in postmenopausal women with HR+ early breast cancer," Yardley observed. "However, musculoskeletal pain is a feature common to all AIs and has been found to occur in 7% to 40% of women receiving AI therapy."

Symptoms, which usually occur within 6 months of starting AI therapy, lead to premature treatment withdrawal in up to 20% of patients, she said.

The present study was conducted to determine whether switching to another AI could improve A/M and allow patients to remain on AI therapy.

Women were deemed eligible for letrozole treatment (2.5 mg/day for 6 months) if they were postmenopausal, HR+, had early-stage breast cancer, and experienced grade 2 to 3 A/M on anastrozole resulting in therapy discontinuation. Grade 2 pain referred to moderate pain; grade 3 pain denoted severe pain.

Patients tolerating letrozole therapy at 6 months had the option of continuing letrozole for their prescribed course of 5 years.

At enrollment, 107 (41.0%) women and 70 (26.8%) women had grade 2 A/M or higher A/M, respectively, versus 61 (23.6%) and 46 (17.8%) at 6 months.

Overall, 228 (87.4%) women remained on letrozole therapy until the end of the 6-month study. This rate is similar to the 71.5% rate reported in the Articular Tolerance of Letrozole (ATOLL) study, which also examined the effect of a switch to letrozole in women on anastrozole who had joint pain that was severe enough to require discontinuation, Yardley observed.

Only 25 (9.6%) of 261 women discontinued treatment due to A/M; another 8 (3.1%) women discontinued for other reasons.

Significant improvements in several quality-of-life measures were documented at 6, 12, and 24 weeks. "Our results suggest that patients who are intolerant of and have discontinued anastrozole due to A/M may better tolerate AI therapy and avoid discontinuation when switched to letrozole," Yardley said.