Real-World Evidence Shows Impact of Musculoskeletal Toxicity of Aromatase Inhibitors on Women with Breast Cancer

Phoebe Starr

February 2013, Vol 4, No 2 - Breast Cancer


San Antonio, TX—Studies have suggested that musculoskeletal toxicity associated with aromatase inhibitor therapy can lead to noncompliance in up to 33% of women with breast cancer. A new, large cohort study at a single regional cancer center showed that the rate of musculoskeletal toxicity in women with early breast cancer who were treated with endocrine therapy was 64%.

The findings were presented at a poster session during the 2012 CTRC-AACR San Antonio Breast Cancer Symposium. Patients taking aromatase inhibitors had almost twice the frequency of musculo­skeletal toxicity as those receiving tamoxifen (Nolvadex; 64% vs 36%, respectively).

These findings are similar to a 2011 report showing that 61% of women receiving aromastase inhibitors had musculoskeletal toxicity in clinical trials and 20% discontinued their therapy because of the toxicity (Gaillard S, et al. Breast Cancer Res. 2011;13:205).

“Despite the high incidence of musculoskeletal toxicity observed in patients taking aromatase inhibitors, the majority continued treatment, with only 22.9% of women discontinuing therapy for this reason,” stated lead investigator Susan F. Dent, MD, BSc, Medical Oncologist at the Ottawa Hospital Cancer Centre, Canada.

The study was based on a retrospective chart review at the Ottawa Hospital Cancer Centre between January 1999 and December 2006. The population included 626 postmenopausal women (mean age, 59 years) with hormone receptor–positive early breast cancer who were treated with endocrine therapy, including at least 1 aromatase inhibitor.

The median follow-up was 98 months, and the median duration of treatment with an aromatase inhibitor was 59 months. The women had a total of 1117 prescriptions that included letrozole (Femara), anastrozole (Arimidex), exemestane (Aromasin), and tamoxifen.

Musculoskeletal toxicity developed in 68% of patients taking letrozole, 47.6% of those taking exemestane, 63.9% of those taking anastrozole, and 36% of those taking tamoxifen. The median times to developing musculoskeletal toxicity were 21 months, 9 months, 23 months, and 23 months, respectively.

The most frequent musculoskeletal toxicities were:

  • Arthralgias, 41%
  • Myalgias, 25%
  • Osteoporosis/osteopenia, 23%
  • Arthritis, 19%.

Treatment was discontinued for these toxicities significantly more often with any aromatase inhibitor than with tamoxifen (14.6% vs 4.8%, respectively; P <.001). Treatment strategies for musculoskeletal toxicity did not significantly impact adherence to therapy, except in the case of exemestane.

Among the group treated with exemestane, the adherence rate with no intervention was 33% and adherence increased to 80% with musculoskeletal toxicity intervention, including mediation and physiotherapy (P <.001).

Longer exposure to any endocrine therapy did not appear to increase the rate of musculoskeletal toxicity. Among this group of women, 51% completed 5 years of endocrine therapy as prescribed.