How much longer is long enough?

How long should postmenopausal women take endocrine therapy after early stage breast cancer? Extended treatment with aromatase inhibition (AI) after 5 years of tamoxifen has been shown to improve disease-free survival (DFS) and even overall survival (OS). However, AI is favored over tamoxifen in post-menopausal women, and it’s less clear if extending AI therapy beyond 5 years is beneficial.  In SALSA, 3486 postmenopausal with hormone receptor (HR)+ breast cancer who completed 5 years of adjuvant endocrine therapy (51% tamoxifen alone, 42% tam + AI) were randomized to an additional 2 years or 5 years of anastrazole. The goal was to determine if improvements in disease outcomes outweighed side effects. They didn’t. There was no difference in DFS or OS, but there was an increase in treatment-related fractures from 4.7 → 6.3%. The NSABP-42 trial also found no improvement in DFS despite a decrease in breast cancer risk with extended AI therapy after prior AI or Tam/AI. In contrast MA.17R did show an improvement in DFS with 10 years of AI therapy, however that seemed to be driven by a reduction in contralateral breast events. Thus, 5 years of extended AI therapy after endocrine therapy seems no better than 2 years, and it further increases the risk of skeletal adverse events. | Gnant, N Engl J Med 2021