The perspective of anti-HER2 therapy for HER2 positive breast cancer

Abstract

Anti-HER2 therapy has been developed during two decade. We have already four agents including trastuzumab(H), lapatinib, pertuzumab(P), T-DM1 for HER2 positive breast cancer. As 1st line therapy for metastatic breast cancer with HER2 positive, H + P + Docetaxel regimen was strongly recommended according to CLEOPATRA study. T-DM1 was recommended as 2nd line therapy for same subtype according to EMILIA study. However, we still have any number of clinical questions (beyond P, best regimen as 1st line for the elderly, et al) which should confirmed by clinical trials. Of course, there also are no precise predictive biomarker of effect by anti-HER2 therapy. However, we have experienced many clinical CR cases which not recur during long time by anti-HER2 therapy. I believe especially some recurrence cases with HER2 enrich subtype will be cured by sensitive anti-HER2 therapy. Anti-HER2 therapy with dual blockade as adjuvant/neoadjuvant therapy was controversial for primary HER2 positive breast cancer. There are some estrangement of long term outcome between ALLTO and Neo ALLTO study. We also have some evidences from NeoLaTH (neoadjuvant study for HER2 positive breast cancer in Japan). Especially, I consider that we should discriminate between HER2 enrich and luminal HER2 subtypes based on clinical behavior and data by many clinical trials. Unfortunately, pCR may not be a predictive marker of PFS or OS according to current trial data for HER2 positive early breast cancer. However, pCR rate is much higher (over 50%) for primary breast cancer with HER2 enrich subtype. We should challenge the way of no surgery by an effective neoadjuvant therapy near future. Already, the clinical studies to evaluate a sensitivity of pCR by some radiological procedures were opened in the world including Japan. In this session, I will propose new strategies (cure and no surgery method for metastatic and primary breast cancer, respectively) for HER2 positive breast cancer using the Anti-HER2 therapy.