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18-05-2018 | HER2-positive breast cancer | Article

Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the “one thousand HER2 patients” project

British Journal of Cancer

Authors: Giuseppe Gullo, Naomi Walsh, David Fennelly, Reetesh Bose, Janice Walshe, Dimitrios Tryfonopoulos, Kate O’Mahony, Lisa Hammond, Nuno Silva, Deirdre McDonnell, Josephine Ballot, Cecily Quinn, Enda W. McDermott, Denis Evoy, Ruth Prichard, James Geraghty, John Amstrong, John Crown

Publisher: Nature Publishing Group UK



The optimal timing of (neo)adjuvant trastuzumab initiation with respect to chemotherapy and surgery remains undefined.


Retrospective analysis of a large institutional database of HER2-positive patients who received anti-HER2 therapy. We included all Stage I to III patients treated with trastuzumab with a minimum follow up of 3 years. The date of first breast biopsy was recorded as initial diagnosis.


A total of 506 patients [adjuvant: 386 (76%)-neo-adjuvant: 120 (24%)] were included. The median time-to-first-trastuzumab (TFT) from diagnosis was 12 weeks (range 1.9–122.3). Median follow-up is 73.3 months (range 1.4–176.3). TFT was significantly shorter in the neo-adjuvant than in the adjuvant cohort (median: 4.4 vs. 14 weeks, p< 0.00001). Despite the neo-adjuvant cohort having significantly more node-positive patients (75 vs. 53%, p < 0.0001), DFS rate (neo-adjuvant: 12.5 vs. adjuvant: 18%, p = 0.094) was numerically superior in neo-adjuvant patients. A TFT ≤ 12 weeks was associated with significantly superior DFS and OS over TFT > 12 weeks. Early concomitant regimens were associated with superior DFS over delayed-concomitant and sequential regimens.


Initiating trastuzumab more than 12 weeks from diagnosis has a negative impact on clinical outcome. Neo-adjuvant anti-HER2 therapy could be the optimal strategy to treat early stage HER2-positive breast cancer.

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