The immune system and response to HER2-targeted treatment in breast cancer.
The monoclonal antibody trastuzumab targets the growth factor receptor HER2 and has profoundly improved the course of disease and survival of women with HER2-overexpressing breast cancer. Because trastuzumab targets aberrant expression of HER2 in tumours addicted to HER2 activation, its clinical activity is credited largely to inhibition of intracellular signalling. A growing body of preclinical and clinical evidence shows that the immune system contributes substantially to the therapeutic effects of trastuzumab and other monoclonal antibodies in vivo. Furthermore, findings indicate that immune-related markers can provide useful predictive information and that increased clinical activity might follow activation of the immune system. Development of immunomodulatory drugs with remarkable activity in many solid tumours defines a scenario in which the combination of immune modulation with trastuzumab, or other HER2-directed drugs, will result in augmented response and clinical outcome.
Department of Medical Oncology, Ospedale San Raffaele, 20132 Milan, Italy.
Giampaolo
G
Bianchini
Department of Medical Oncology, Ospedale San Raffaele, 20132 Milan, Italy. Electronic address: gianni.luca@hsr.it.
Luca
L
Gianni
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D058990:Molecular Targeted Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000068878:Trastuzumab; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human