A clinical trial in a racially diverse group of postmenopausal women with early breast cancer to study severe pain in the bones, muscles, ligaments, tendons, and nerves caused by aromatase inhibitor treatment has found that the symptoms were more commonly reported in Black and Asian patients than White patients. However, aromatase inhibitor discontinuation rates were similar among the three groups, according to data presented by Vered Stearns, MD, and colleagues during the 2021 ASCO Annual Meeting (Abstract 12003).

Vered Stearns, MD

E1Z11 Trial

Previous similar studies mainly included White women, whereas the E1Z11 study set individual accrual goals for self-reported Black, Asian, and White participants. Total enrollment was 1,046 patients, including Black (n = 201), Asian (n = 205), and White (n = 640) participants. Women were eligible for the study if they had early (stage I–III) hormone receptor–positive breast cancer, were postmenopausal, had completed planned local therapy, and had not received prior aromatase inhibitor therapy as first-line treatment.

Aromatase inhibitors stop estrogen production and are widely prescribed in postmenopausal women, typically for 5 or more years after surgery/chemotherapy, to prevent a breast cancer recurrence. Yet, their effectiveness can be compromised, because 40% to 50% of women stop treatment early due to the severe pain caused by aromatase inhibitor–associated musculoskeletal symptoms. The syndrome was not recognized during the U.S. Food and Drug Administration registration trials for this class of drugs, which includes anastrozole, exemestane, and letrozole.

Rates of Musculoskeletal Symptoms

The E1Z11 study collected data from women during their first year of aromatase inhibitor therapy.

More Black and Asian women developed severe musculoskeletal pain during this time than White women—48%, 50%, and 38%, respectively. Rates of aromatase inhibitor discontinuation within 1 year were similar across the three cohorts—10%, 12%, and 13%.

E1Z11 participants also contributed blood samples to build a biobank to examine germline genetic variants in DNA for this and future research. Genotyping success rates were high across all cohorts (> 95%). This analysis was not able to demonstrate associations between aromatase inhibitor–associated musculoskeletal symptom development and 10 germline DNA variants thought to be predictors. However, the authors reported that one gene—rs2296972/HTR2A—warrants further study.

Participants also completed extensive questionnaires about their symptoms, quality of life, and anxiety about cancer recurrence. The surveys occurred every 3 months during the first year of aromatase inhibitor treatment. Survey completion rates were high across all cohorts at every time point: 98% at baseline, 93% at 3 months, 89% at 6 months, 88% at 9 months, and 90% at 12 months.

Dr. Stearns, of Johns Hopkins University, commented, "More Black and Asian postmenopausal women than White women with early breast cancer developed severe musculoskeletal pain within the first year of aromatase inhibitor therapy. However, the rates of early discontinuation of therapy were similar across the three groups. The E1Z11 biospecimens bank and patient-reported outcomes data are a treasure trove for future discovery across the three racial cohorts. For example, there will be data from this trial on the tolerability of aromatase inhibitors from the patient's perspective, yielding important insights on how to support women from [minority] groups to gain maximum benefit from treatment."

Disclosure: For full disclosures of the study authors, visit coi.asco.org.