Adherence to Adjuvant Endocrine Therapy and Survival Among Older Women with Early-Stage Hormone Receptor-Positive Breast Cancer

Clin Drug Investig. 2023 Mar;43(3):167-176. doi: 10.1007/s40261-023-01247-w. Epub 2023 Feb 6.

Abstract

Background and objective: Although improving adherence to adjuvant endocrine therapies (AETs) is critical to ensure better patient outcomes, the evidence is still lacking on differences in 5-year AET adherence trajectories. This study aimed to estimate the time trend of adherence by the type of individual AET and the association of adherence to AETs with overall survival among older women with hormone receptor-positive breast cancer.

Methods: This study used the Surveillance, Epidemiology, and End Results-Medicare database 2006-2016. We included women aged ≥ 65 years with newly diagnosed hormone receptor-positive breast cancer and who had initiated AET (anastrozole, letrozole, exemestane, or tamoxifen). Adherence to AETs was defined as the proportion of days covered that was calculated for the follow-up period (5 years). The overall survival time was defined as the time from the date of AET initiation to death. The linear mixed models with repeated measures were used to estimate the changes in adherence to AETs. The Cox proportional hazard model was used to assess the relationships (hazard ratio [HR] and 95% confidence interval [CI]) between adherence to AETs and death.

Results: A total of 11,617 patients were included. Anastrozole was the most commonly used (n = 6,908), followed by letrozole (n = 2,586), tamoxifen (n = 1,750), and exemestane (n = 373). The mean (standard deviation) of proportion of days covered for 5 years was 57.4 (34.6), indicating the highest proportion of days covered in the anastrozole group [61.1 (34.1)] and the lowest proportion of days covered in the exemestane group [44.0 (35.1)]. Overall, adherence to AET decreased over the 5-year follow-up period in all AET groups, but the decrease in the tamoxifen group was steeper (42.3% decreased) compared with other AETs. Anastrozole, letrozole, and exemestane groups were associated with a lower risk of death compared with the tamoxifen group (HR = 0.80, 95% CI 0.71-0.89 for anastrozole; HR = 0.82, 95% CI 0.72-0.93 for letrozole; HR = 0.82, 95% CI 0.63-1.07 for exemestane).

Conclusions: Patients who initiated with tamoxifen had a steeper decrease in adherence over the 5 years compared with anastrozole, letrozole, and exemestane groups. Furthermore, higher adherence was associated with a decreased risk of mortality. Physicians should be cognizant of decreasing adherence over time and choose effective treatment options with minimal side-effect profiles to better support adherence by patients with breast cancer.

MeSH terms

  • Aged
  • Anastrozole
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Female
  • Humans
  • Letrozole
  • Medicare
  • Nitriles
  • Tamoxifen / therapeutic use
  • United States

Substances

  • Anastrozole
  • Letrozole
  • Aromatase Inhibitors
  • 2-aminoethanethiosulfonic acid
  • Tamoxifen
  • Nitriles