Is HER2-positive metastatic breast cancer still an incurable disease?

Abstract

The discovery of the HER2 oncogene was one of the most important advances in breast cancer research. 20 years ago, the advent of trastuzumab 1 Slamon DJ Leyland-Jones B Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344: 783-792 Crossref PubMed Scopus (9343) Google Scholar started a revolution that has continued with the introduction of additional effective targeted agents. Dual anti-HER2 targeting with trastuzumab plus pertuzumab in addition to docetaxel is an unquestionable step forward in the field. Since the publication of the first results of the CLEOPATRA trial in 2012, 2 Baselga J Cortés J Kim S-B et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012; 366: 109-119 Crossref PubMed Scopus (1901) Google Scholar the pertuzumab-based regimen has become the new standard first-line treatment for patients with HER2-positive metastatic breast cancer. 3 Cardoso F Senkus E Costa A et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol. 2018; 29: 1634-1657 Summary Full Text Full Text PDF PubMed Scopus (730) Google Scholar , 4 Giordano SH Temin S Chandarlapaty S et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: ASCO Clinical Practice Guideline update. J Clin Oncol. 2018; 36: 2736-2740 Crossref PubMed Scopus (124) Google Scholar Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 studyOur analysis shows that the previously observed improvements in overall survival with pertuzumab, trastuzumab, and docetaxel versus placebo, trastuzumab, and docetaxel were maintained after a median of more than 8 years of follow-up. The long-term safety and cardiac safety profiles of pertuzumab, trastuzumab, and docetaxel were maintained in the overall safety population and within crossover patients. HER2-targeted therapy has changed the natural history of HER2-positive metastatic breast cancer, with the dual blockade of pertuzumab and trastuzumab, with docetaxel, demonstrating an 8-year landmark overall survival rate of 37%. Full-Text PDF