Hard truth comes in soft text.
The Study: Tamoxifen is the best endocrine therapy for these women, right? Actually, no. The 2014 combined reporting of the SOFT and TEXT trials comparing ovarian suppression in combo with either tamoxifen or exemestane (plus a third arm of tamoxifen alone in SOFT) demonstrated a 4% absolute benefit in disease-free survival (DFS) at 5 years with ovarian suppression + exemestane. By ovarian suppression we mean just what you think: a GnRH agonist, bilateral oopherectomies or even ovarian radiation. The enrollees were pretty heterogeneous, making interpreting those results pretty confusing. To clarify things, an updated combined analysis is now here, and it promises...more confusion. Combining the two trials was clearly an afterthought in hopes of shoring up significant values, but that it did. DFS at 8 years was significantly better with combo ovarian suppression + tamoxifen (83%) than tamoxifen alone (79%), and ovarian suppression + exemestane still proved best of all (87%). In fact, this relative benefit with aromatase inhibition over tamoxifen (when given with ovarian suppression in this case) isn’t much different than that achieved among post-menopausal women.
Bottom Line: Ovarian suppression with exemestane affords the best DFS among endocrine therapies available for premenopausal breast cancer—with highest absolute benefit, as always, achieved among those as highest absolute risk. | Francis, N Engl J Med 2018