Treatment Efficacy, Adherence, and Quality of Life Among Women Younger Than 35 Years in the International Breast Cancer Study Group TEXT and SOFT Adjuvant Endocrine Therapy Trials

Abstract

Purpose To describe benefits and toxicities of adjuvant endocrine therapies in women younger than 35 years with breast cancer (n = 582) enrolled in the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT). Methods In SOFT, women still premenopausal after surgery with or without chemotherapy were randomly assigned to tamoxifen alone, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. In TEXT, all received OFS with or without concomitant chemotherapy and were randomly assigned to exemestane plus OFS or tamoxifen plus OFS. We summarize treatment efficacy, quality of life, and adherence of the cohort of women younger than 35 years in SOFT and TEXT, alongside data from the cohort of older premenopausal women. Results For 240 human epidermal growth factor receptor 2-negative patients younger than 35 years enrolled in SOFT after receiving chemotherapy, the 5-year breast cancer-free interval (BCFI) was 67.1% (95% CI, 54.6% to 76.9%) with tamoxifen alone, 75.9% with tamoxifen plus OFS (95% CI, 64.0% to 84.4%), and 83.2% with exemestane plus OFS (95% CI, 72.7% to 90.0%). For 145 human epidermal growth factor receptor 2-negative patients younger than 35 years in TEXT, 5-year BCFI was 79.2% (95% CI, 66.2% to 87.7%) with tamoxifen plus OFS and 81.6% (95% CI, 69.8% to 89.2%) with exemestane plus OFS. The most prominent quality of life symptom for patients younger than 35 years receiving OFS was vasomotor symptoms, with the greatest worsening from baseline at 6 months (on the order of 30 to 40 points), but loss of sexual interest and difficulties in becoming aroused were also clinically meaningful (≥ 8-point change). The level of symptom burden was similar in older premenopausal women. A total of 19.8% of women younger than 35 years stopped all protocol-assigned endocrine therapy early. Conclusion In women younger than 35 years with hormone receptor-positive breast cancer, adjuvant OFS combined with tamoxifen or exemestane produces large improvements in BCFI compared with tamoxifen alone. Menopausal symptoms are significant but are not worse than those seen in older premenopausal women.

Fig 1.

Flow diagram of analysis populations. (*) Quality-of-life (QoL) populations were 87% of the intention-to-treat (ITT) populations, after exclusion of patients having eligibility exemption and of patients at centers not compliant with QoL submission.^, HER2, human epidermal growth factor receptor 2; SOFT, Suppression of Ovarian Function Trial; TEXT, Tamoxifen and Exemestane Trial.

Fig 2.

Kaplan-Meier estimates of breast cancer–free interval (BCFI) among patients with human epidermal growth factor receptor 2–negative disease in the chemotherapy cohorts of the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT), according to age at random assignment and treatment assignment. Median follow-up was 5.6 years in SOFT and 6.0 years in TEXT. (A, B) SOFT prior chemotherapy, age younger than 35 years and ≥ 35 years. (C, D) TEXT chemotherapy, age younger than 35 years and ≥ 35 years. E, exemestane; OFS, ovarian function suppression; T, tamoxifen.

Fig 3.

Change in quality-of-life symptom and global indicator scores from baseline (mean with 95% CI), for 291 patients in the Suppression of Ovarian Function Trial who were younger than 35 years at random assignment and had received prior chemotherapy. Plus or minus 8 is the minimal clinical meaningful change of quality-of-life scores, indicated by dashed vertical lines. OFS, ovarian function suppression.

Fig 4.

Adherence with protocol-assigned endocrine therapy according to age at random assignment. (A) Cumulative incidence of cessation of assigned oral endocrine therapy (exemestane or tamoxifen). (B) Cumulative incidence of cessation of medical ovarian function suppression (OFS) by gonadotropin-releasing hormone (GnRH) agonist; patients switching to permanent OFS are not considered as having ceased medical OFS. (C) Cumulative incidence of permanent ovarian ablation by bilateral oophorectomy or ovarian irradiation.

Fig A1.

Kaplan-Meier estimates of distant recurrence-free interval among patients with human epidermal growth factor receptor 2–negative disease in the chemotherapy cohorts of the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT), according to age at random assignment and treatment assignment. Median follow-up was 5.6 years in SOFT and 6.0 years in TEXT. (A, B) SOFT prior chemotherapy, age younger than 35 years and ≥ 35 years. (C, D) TEXT chemotherapy, age younger than 35 years and ≥ 35 years. E, exemestane; OFS, ovarian function suppression; T, tamoxifen.