Trastuzumab-based therapy for patients with HER2-positive breast cancer: from early scientific development to foundation of care.
Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression occurs in 20% to 25% of breast tumors, often leading to an aggressive disease course and poor clinical outcomes. Successful targeting of HER2-positive tumors in preclinical models with trastuzumab has translated to the clinic. In HER2-positive metastatic breast cancer (MBC), trastuzumab provides significant clinical benefit as a monotherapy and in combination with numerous chemotherapies. In the phase III trial of first-line trastuzumab plus chemotherapy, overall response rate (ORR; 50%, P < 0.001), overall survival (25.1 months vs. 20.3 months, P = 0.046) and time to disease progression improved significantly compared with chemotherapy alone (7.4 vs. 4.6 months, P < 0.001), and second-line trastuzumab use after prior trastuzumab has resulted in ORRs of up to 50%. Clinical success in the metastatic setting provided the rationale for assessing trastuzumab in early breast cancer. Four large trials of adjuvant trastuzumab demonstrated significant improvements in disease-free survival (33%-52%) and overall survival (34%-41%) despite tumor size, nodal or hormone-receptor status, and age. New approaches to maximize the clinical benefit of trastuzumab-based therapy are under investigation and include novel combinations with other targeted therapies such as bevacizumab, pertuzumab, and lapatinib.
Brufsky
Adam
A
School of Medicine, University of Pittsburgh Cancer Institute, Magee Women's Hospital, Pittsburgh, PA, USA. brufskyam@upmc.edu
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab