Adjuvant Tamoxifen Plus Ovarian Function Suppression Versus Tamoxifen Alone in Premenopausal Women With Early Breast Cancer: Patient-Reported Outcomes in the Suppression of Ovarian Function Trial

Abstract

Purpose: The Suppression of Ovarian Function trial showed improved disease control for tamoxifen plus ovarian function suppression (OFS) compared with tamoxifen alone for the cohort of premenopausal patients who received prior chemotherapy. We present the patient-reported outcomes.

Patients and methods: The quality-of-life (QoL) analysis includes 1,722 of 2,045 premenopausal patients with hormone receptor-positive breast cancer randomly assigned to receive adjuvant treatment with 5 years of tamoxifen plus OFS or tamoxifen alone. Chemotherapy use before enrollment was optional. Patients completed a QoL form consisting of global and symptom indicators at baseline, every 6 months for 24 months, and annually during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6, 24, and 60 months with mixed models for repeated measures with and without chemotherapy and overall.

Results: Patients on tamoxifen plus OFS were more affected than patients on tamoxifen alone by hot flushes at 6 and 24 months, by loss of sexual interest and sleep disturbance at 6 months, and by vaginal dryness up to 60 months. Without prior chemotherapy, patients on tamoxifen alone reported more vaginal discharge over the 5 years than patients on tamoxifen plus OFS. Symptom-specific treatment differences at 6 months were less pronounced in patients with prior chemotherapy. Changes in global QoL indicators from baseline were small and similar between treatments over the whole treatment period.

Conclusion: Overall, OFS added to tamoxifen resulted in worse endocrine symptoms and sexual functioning during the first 2 years of treatment, with variable magnitudes of treatment differences. Short-term differences in symptom-specific QoL, treatment burden, and coping effort between treatment groups were less pronounced for patients with prior chemotherapy, the cohort that benefited most from OFS in terms of disease control.

Trial registration: ClinicalTrials.gov NCT00066690.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2016 by American Society of Clinical Oncology.

Figures

Fig 1.

CONSORT flowchart to identify the intent-to-treat (ITT) quality-of-life population (N = 3,066). OFS, ovarian function suppression; QoL, quality of life; SOFT, Suppression of Ovarian Function Trial.

Fig 2.

(A) Scores for hot flushes (mean with 95% CIs; higher score indicates better condition) from baseline to 60 months according to treatment assignment and chemotherapy cohort. (B) Change in hot flush scores from baseline to 6, 24, and 60 months according to chemotherapy cohort. (C) Scores for loss of sexual interest (mean with 95% CIs; higher score indicates better condition) from baseline to 60 months according to chemotherapy cohort. (D) Change in scores for loss of sexual interest from baseline to 6, 24, and 60 months according to chemotherapy cohort. The vertical line at ± 8 indicates the minimal clinically meaningful change in quality-of-life (QoL) scores. Chemo, chemotherapy; OFS, ovarian function suppression; T, tamoxifen

Fig 2.

(A) Scores for hot flushes (mean with 95% CIs; higher score indicates better condition) from baseline to 60 months according to treatment assignment and chemotherapy cohort. (B) Change in hot flush scores from baseline to 6, 24, and 60 months according to chemotherapy cohort. (C) Scores for loss of sexual interest (mean with 95% CIs; higher score indicates better condition) from baseline to 60 months according to chemotherapy cohort. (D) Change in scores for loss of sexual interest from baseline to 6, 24, and 60 months according to chemotherapy cohort. The vertical line at ± 8 indicates the minimal clinically meaningful change in quality-of-life (QoL) scores. Chemo, chemotherapy; OFS, ovarian function suppression; T, tamoxifen

Fig 3.

Change in quality-of-life (QoL) symptom indicator scores from baseline to 6, 24, and 60 months, according to treatment assignment, overall across chemotherapy cohorts. The vertical line at ± 8 indicates the minimal clinically meaningful change in QoL scores. OFS, ovarian function suppression.

Fig 4.

Change in quality-of-life (QoL) global indicator scores from baseline to 6, 24, and 60 months, according to treatment assignment, overall across chemotherapy cohorts. The vertical line at ± 8 indicates the minimal clinically meaningful change in QoL scores. OFS, ovarian function suppression.

Fig 5.

Change in quality-of-life (QoL) symptom and global indicator scores from baseline to 6 months according to chemotherapy cohorts (side by side). The vertical line at ± 8 indicates the minimal clinically meaningful change in QoL scores. The baseline scores for each indicator are summarized according to cohort and treatment in Table 2. OFS, ovarian function suppression.

Fig A1.

Change of symptom and global quality-of-life (QoL) indicator scores from baseline to 6, 24, and 60 months, according to treatment assignment, for the three treatment assignments in the Suppression of Ovarian Function Trial, overall across chemotherapy cohorts. The vertical line at ± 8 indicates the minimal clinically meaningful change in QoL scores. E, exemestane; OFS, ovarian function suppression; T, tamoxifen.

Fig A2.

(A) Change of symptom and global quality-of-life (QoL) indicator scores from baseline to 6, 24, and 60 months, according to treatment assignment, for the three treatment assignments in the no prior chemotherapy cohort in the Suppression of Ovarian Function Trial (SOFT) trial. (B) Change of symptom and global QoL indicator scores from baseline to 6, 24, and 60 months, according to treatment assignment, for the three treatment assignments in the prior chemotherapy cohort in SOFT trial. The vertical line at ± 8 indicates the minimal clinically meaningful change in QoL scores. E, exemestane; OFS, ovarian function suppression; T, tamoxifen.

Fig A2.

(A) Change of symptom and global quality-of-life (QoL) indicator scores from baseline to 6, 24, and 60 months, according to treatment assignment, for the three treatment assignments in the no prior chemotherapy cohort in the Suppression of Ovarian Function Trial (SOFT) trial. (B) Change of symptom and global QoL indicator scores from baseline to 6, 24, and 60 months, according to treatment assignment, for the three treatment assignments in the prior chemotherapy cohort in SOFT trial. The vertical line at ± 8 indicates the minimal clinically meaningful change in QoL scores. E, exemestane; OFS, ovarian function suppression; T, tamoxifen.