Maximizing the response to Herceptin therapy through optimal use and patient selection.
The aggressiveness of human epidermal growth factor receptor-2 (HER2)-positive breast cancer and the poor prognosis of women with this disease demand the availability of accurate and reliable tests for HER2 status and the optimization of HER2-targeted therapy. The distinctive clinical pattern of HER2-positive breast cancer underlines the importance of testing for HER2 status and efforts are ongoing to validate the two major methods in use-immunohistochemistry (IHC), which measures cell membrane HER2 expression, and fluorescence in situ hybridization (FISH), which measures gene copy number. Clinical trial results demonstrate that there is an association between strong HER2 overexpression (IHC 3+) and optimal response to therapy with the novel recombinant HER2 antibody Herceptin. High levels of concordance between IHC 3+ and FISH-positive status have been observed, and response to treatment with Herceptin is similar for patients whose breast cancers are IHC 3+ and those who are FISH-positive. Observations to date have led to the formulation of an algorithm for HER2 status determination and Herceptin use which recommends that: (i) the HER2 status of all women with breast cancer be determined at presentation, (ii) all IHC 3+ and FISH-positive patients with metastatic disease should receive Herceptin, (iii) Herceptin should be used early in the course of metastatic breast cancer and preferably first line, and (iv) Herceptin therapy should be continued until disease progression.
Leyland-Jones
B
B
Department of Oncology, McGill University, Montreal, Quebec, Canada. leylandj@med.mcgill.ca
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018579:Patient Selection; 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