Immunologic profiling and clinical outcome in HER2+ breast cancer patients treated in a neoadjuvant phase II study: A step forward to understand trastuzumab activity.

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e11083 Background: A phase II study was performed to assess the role of patients’ immune profile in the activity of a trastuzumab (T) based, non anthracycline containing neoadjuvant chemotherapy (NC) regimen in breast cancer (BC) patients (pts). Methods: Newly diagnosed T2-3 HER2+ BC pts received a 12 week NC with weekly paclitaxel (P) and T, which was continued for further 12 weeks before surgery in the absence of progression (PRO). Further 12 weeks of the same therapy was planned after surgery and then T alone to 1 year of treatment ± hormonal therapy and radiotherapy. In case of PRO, T was discontinued and anthracyclines were planned. Blood samples were collected at diagnosis and every 3 months for 1 year then yearly. The % of NK cells, T cells and Treg cells was evaluated by flow cytometry, and serum levels of 9 cytokines were assessed by SearchLight multiplex array technology. In vitro T-mediated, antibody-dependent cell cytotoxicity (ADCC) was also assessed using patients’ PBMCs. Results: From July 2006 32 pts were enrolled, 31 were evaluable (1 ongoing). Pathological complete response (pCR) was reported in 15 pts (48%, 95% CI: 31-66%), objective overall clinical response was observed in 30 pts (97%, 95% CI: 91-100%). No cardiotoxicity occurred. In 3 cases (9.7%) PRO occurred at 26.3 months median follow-up. At diagnosis, pts showed an immune profile similar to that of healthy women, whereas higher numbers of Treg cells (p=0.02), NK cells (p=0.03), lower T cell numbers (p<0.01) and lower amounts of serum IL-2, IL-6, and IL-8 were found in a concomitant control group of untreated HER2- pts. Notably, study pts achieving pCR presented higher efficiency of basal T-mediated ADCC compared to pts with partial responses (p=0.05). The treatment induced a progressive increase in the number of NK cells and in the efficiency of T-mediated ADCC. Conclusions: NC with P and T induces high rates of pCR with no cardiotoxicity. This clinical efficacy is favored by the retained immunological proficiency of HER2+ pts, who may benefit from the immunomodulating properties of T started early. Whether T-mediated ADCC is significant also for event-free survival is under evaluation.