The combined analysis of the TEXT and SOFT trials showed a significant disease-free survival benefit with exemestane plus ovarian function suppression (OFS) compared with tamoxifen plus OFS in premenopausal women with hormone-receptor-positive breast cancer, providing a new treatment option for these patients who receive OFS as part of adjuvant endocrine therapy.1 In both trials, the decision to give chemotherapy was made by the physician and patient. In TEXT, chemotherapy was given concurrently with OFS after randomisation.2 In SOFT, patients who received chemotherapy were eligible for randomisation only if they remained premenopausal after completion.2
Tamoxifen has been compared extensively with aromatase inhibitors in postmenopausal patients. Patient-reported symptoms related to endocrine therapy were assessed in the ATAC trial3, 4 and the IES5 trial. The results of these trials showed no major differential effects of the endocrine agents on overall quality of life (QoL) or total symptom scores. Patients reported hot flushes as the most prevalent side-effect of treatment, but indicated no differences between tamoxifen and anastrozole3, 4 or exemestane.5 Self-reported gynaecological symptoms (ie, vaginal dryness, diminished libido, and pain with intercourse) were more frequent with anastrozole than with tamoxifen, whereas dizziness, cold sweats, and vaginal discharge were more frequent with tamoxifen.3, 4 Comparisons of exemestane and tamoxifen showed no differences for any of the endocrine symptoms except vaginal discharge, which was more common with tamoxifen for up to 24 months after 2–3 years of treatment.5 Patient-reported bone or joint pain was not assessed in these trials.
Research in context
Evidence before this study
We searched PubMed for clinical trials published in English between Jan 1, 1998, and Jan 1, 2003, and updated the search on Feb 26, 2015, in which patient-reported symptoms and quality of life (QoL) were assessed in premenopausal women with early breast cancer who were undergoing adjuvant endocrine treatment. We used the search terms “premenopausal”, “tamoxifen”, “aromatase inhibitors”, “QoL”, and “patient-reported outcome”. We manually reviewed the results and found no randomised phase 3 trials reporting patient-reported symptoms and QoL for the specific comparison of tamoxifen with an aromatase inhibitor in premenopausal women. Existing data were from postmenopausal women or placebo-controlled breast cancer prevention trials.
Added value of this study
In the TEXT and SOFT trials, patients assigned exemestane plus ovarian function suppression (OFS) reported greater bone or joint pain, vaginal dryness, loss of sexual interest, and difficulties becoming aroused, whereas patients assigned tamoxifen plus OFS were more affected by hot flushes and sweats. Global QoL domains were similar between the randomised treatment groups. The different effects on endocrine symptoms were only partly consistent with the findings of previous trials of an aromatase inhibitor compared with tamoxifen in postmenopausal patients (without OFS). In the IES trial, comparisons between patients receiving exemestane and tamoxifen showed no differences between treatments for any of the endocrine symptoms except vaginal discharge, which was greater with tamoxifen up to 24 months after 2–3 years of treatment. In the ATAC trial, self-reported gynaecological symptoms were more frequent with anastrozole than with tamoxifen, whereas dizziness, cold sweats, and vaginal discharge were more frequent with tamoxifen. Patient-reported bone or joint pain was not assessed in these trials.
Implication of all the available evidence
The combined analysis of the TEXT and SOFT trials showed a disease-free survival benefit for exemestane plus OFS compared with tamoxifen plus OFS in premenopausal patients with hormone-receptor-positive breast cancer, suggesting a new treatment option for premenopausal women who receive OFS as part of adjuvant endocrine therapy. From a QoL perspective, there is no strong indication to favour either exemestane plus OFS or tamoxifen plus OFS. The different effects of the two treatments on endocrine symptoms should be discussed with each patient individually.
The findings from placebo-controlled breast cancer prevention trials in postmenopausal women showed more vasomotor6, 7 and gynaecological symptoms, and sexual problems with tamoxifen,6 and worse menopausal-related QoL with exemestane.8 In the MAP.3 trial,9 exemestane had small negative effects on vasomotor symptoms, sexual symptoms, and pain, which occurred mainly in the first 6 months to 2 years after random assignment. No treatment differences were noted in general QoL domains.9
Little is known about the effect of chemotherapy on patients' perception of endocrine symptoms. In the ZIPP trial,10 the type of endocrine therapy given (goserelin, goserelin plus tamoxifen, or tamoxifen alone) had different effects on patient-reported symptoms only in patients who did not receive chemotherapy.10
The QoL analysis, a pre-planned secondary analysis, in the TEXT and SOFT trials was done in parallel with the efficacy analysis1 to elucidate differential effects of exemestane compared with tamoxifen on QoL in premenopausal patients who are treated with OFS during adjuvant endocrine therapy. Here, we present the combined patient-reported outcomes from the TEXT and SOFT trials.