Background: Neo-adjuvant chemotherapy (NAC) can facilitate breast conservation, allows
in vivo testing of chemotherapy sensitivity and provides a route to accelerated approval of new therapies.
For HER2 positive breast cancer, the anti-HER2 monoclonal antibody, trastuzumab, is a standard
component of neo-adjuvant therapy.
Pertuzumab is an anti-HER2 monoclonal antibody with a distinct binding site to trastuzumab, which
prevents HER2 receptor dimerisation. In early breast cancer, the addition of pertuzumab to docetaxel
and trastuzumab resulted in a higher rate of pathological complete response (pCR), leading to accelerated
approval in many territories. T-DM1 is a novel antibody-drug conjugate, combining trastuzumab
with a potent cytotoxic, DM1, a maytansine derivative, via a stable thioether linker. In advanced
breast cancer (ABC), T-DM1 improves survival compared to standard 2nd or 3rd line regimens, but not
compared to first line chemotherapy plus trastuzumab. The KRISTINE trial investigated the combination
of T-DM1 with pertuzumab compared to standard chemotherapy plus trastuzumab and pertuzumab
in early breast cancer.
Methods: This review summarises the data supporting current standards in the neo-adjuvant treatment
of HER2 positive early breast cancer and the impact of the KRISTINE trial results.
Results: T-DM1 with pertuzumab did not improve pCR over standard therapy, although the novel
combination was better tolerated, and a sub-group of patients (44%) achieved pCR with the systemic
chemotherapy-free regimen. This suggests that not all HER2 positive early breast cancer patients require
systemic chemotherapy and provides the potential, if these patients can be identified up-front, to
Conclusion: Although the KRISTINE trial results have not changed the standard of care for the neoadjuvant
management of HER2 positive breast cancer, further research is needed to determine whether
T-DM1 could be used to de-escalate NAC for selected patients.