. 2019 Jul; 20(7):e390-e396.
doi: 10.1016/S1470-2045(19)30158-5.

Changing frameworks in treatment sequencing of triple-negative and HER2-positive, early-stage breast cancers

Lajos Pusztai 1 Julia Foldi 2 Arjun Dhawan 2 Michael P DiGiovanna 2 Eleftherios P Mamounas 3 
  • PMID: 31267973
  •     13 citations


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.

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