The gist: A new treatment approach might improve outcomes for certain premenopausal women with breast cancer. In the new approach a drug, surgery, or radiation is used to make the patient’s ovaries stop producing estrogen. In a clinical trial, some premenopausal women with breast cancer were treated with so-called “ovarian suppression” along with the drug exemestane. Others were treated with ovarian suppression along with the drug tamoxifen, and others took only tamoxifen. Ovarian suppression did not improve outcomes for all women in the trial, but it did improve outcomes for premenopausal women with early-stage, hormone receptor-positive breast cancer who had already received chemotherapy after surgery. These women did better with ovarian suppression plus exemestane than they did with ovarian suppression with tamoxifen or tamoxifen alone.
“In the phase III SOFT trial reported in The New England Journal of Medicine, Francis et al found that the addition of ovarian suppression to tamoxifen did not improve disease-free survival among all women with premenopausal breast cancer but appeared to have a beneficial effect in those who had received adjuvant chemotherapy and remained premenopausal. Treatment with exemestane plus ovarian suppression vs tamoxifen alone was associated with significantly better outcomes in this higher-risk group.
“In the study, 3,066 premenopausal women with breast cancer were randomly assigned between December 2003 and January 2011 to receive 5 years of tamoxifen (n = 1,021), tamoxifen plus ovarian suppression (n = 1,024), or exemestane plus ovarian suppression (n = 1,021). Randomization was stratified by receipt or nonreceipt of adjuvant chemotherapy. Ovarian suppression was achieved by triptorelin treatment, bilateral oophorectomy, or bilateral ovarian irradiation. Patients had a median age of 43 years, 46.7% of the patients had not received prior chemotherapy, 53.3% had received prior chemotherapy and remained premenopausal, and 34.9% of patients had node-positive disease.
“The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival vs tamoxifen alone. The study was originally designed to compare disease-free survival between the three treatment groups with three pairwise comparisons. However, enrolled patients were older and had lower-risk characteristics than anticipated and the rate of disease-free survival was higher than expected. A protocol amendment to the statistical analysis plan was adopted in 2011 that designated the test of superiority of tamoxifen/ovarian suppression over tamoxifen alone as the primary analysis and the comparison of exemestane/ovarian suppression vs tamoxifen alone as a secondary analysis…
“The investigators concluded: ‘Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression.’ “