• Alicia Fc Okines.
• The Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ. United Kingdom.
• Rev Recent Clin Trials. 2017 Jan 1; 12 (3): 216-222.

BackgroundNeo-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.MethodsThis 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.ResultsT-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 de-escalate therapy.ConclusionAlthough 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.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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