Fine-Tuning Adjuvant Endocrine Therapy for Early-Stage Breast Cancer: An Expert Consensus on Open Issues for Future Research.

After decades of research, improving the efficacy of adjuvant endocrine therapy (ET) for early-stage breast cancer (BC) becomes increasingly difficult. Beyond technological breakthroughs and the availability of new classes of drugs, further improvement of adjuvant ET will require applying a rigorous research approach in poorly investigated areas. We critically discuss some key principles that should inform future research to improve ET efficacy, including identifying specific subgroups of patients who can benefit from escalating or de-escalating approaches, optimizing available and new treatment strategies for different clinical contexts, and dissecting the direct and indirect biological effects of therapeutic interventions. Four main issues regarding adjuvant ET were identified as relevant areas where a better application of such principles can provide positive results in the near future: i) tailoring the optimal duration of adjuvant ET; ii) optimizing ovarian function suppression for pre-menopausal women; iii) dissecting the biological effects of estrogen receptor manipulation; and iv) refining the selection of patients to candidate for treatments escalation.