Changing Frameworks in Treatment Sequencing of Triple-negative and HER2-positive, Early-stage Breast Cancers

Important results are emerging from clinical trials showing that surgery followed by chemotherapy might not be the optimal strategy to maximise a patient's chance of survival from triple-negative or HER2-positive breast cancers. Administering chemotherapy before surgery provides an opportunity to directly observe the efficacy of a particular chemotherapy regimen. Patients who have extensive residual invasive cancer after neoadjuvant chemotherapy are at a high risk of recurrence for metastatic disease, which, in turn, make these patients ideal candidates for clinical trials. Two important clinical trials, CREATE-X (UMIN000000843) and KATHERINE (NCT01772472), have shown improved disease-free survival with postoperative capecitabine and ado-trastuzumab emtansine in patients with either triple-negative or HER2-positive breast cancer who had residual disease after neoadjuvant chemotherapy. The opportunity for residual-disease guided therapy, as observed in these trials, is lost when patients undergo surgery first. In this Personal View, we discuss the clinical implications of the CREATE-X and KATHERINE trials and place them into context with other developments in the adjuvant setting of early-stage breast cancer. We suggest that neoadjuvant systemic therapy should be considered as the new standard of care for HER2-positive and oestrogen receptor negative breast cancer, even for patients who present with operable (T1 or T2) disease.