HER2+ breast cancer: how to evaluate?
Approximately 15%-30% of breast cancers have overexpression or amplification of human epidermal growth factor receptor 2 (HER2), which is associated with a worse prognosis in the absence of therapy. While HER2 testing is common there are issues associated with its sensitivity and specificity, which may impact the perceived usefulness of treatments. The objectives of this review are to understand the characteristics and peculiarities of HER2+ breast cancer, and to discuss the issues associated with the correlation of HER2 immunogenicity with therapeutic response, especially of trastuzumab. There are two issues associated with the correlation between HER2 immunogenicity and therapeutic response: possible resistance to trastuzumab through lack of phosphatase and tensin analog or receptor expression, and nonspecific or insensitive measurement of HER2 expression. These issues can be addressed through the evaluation of other factors in addition to HER2 status at diagnosis, and improvements in the performance and validation of HER2 testing. It is important that HER2 tests are of the highest quality and that laboratories performing the tests are assessed and validated correctly. Pathologists must proactively monitor the quality of their tests and oncologists should ensure that all breast cancer cases are assessed for HER2, as only then can the patients benefit from specific and appropriate therapy.
Schmitt
Fernando
F
IPATIMUP, Institute of Molecular Pathology and Immunology and Medical Faculty, University of Porto, Porto, Portugal. fernando.schmitt@ipatimup.pt
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012680:Sensitivity and Specificity; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008565:Membrane Proteins; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C446603:TPTE protein, human