title: Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?
abstract: This study evaluated by immunohistochemistry (IHC) immune cell response during neoadjuvant primary systemic therapy (PST) with trastuzumab in patients with HER2-positive primary breast cancer. In all, 23 patients with IHC 3+ primary breast cancer were treated with trastuzumab plus docetaxel. Pathological complete and partial responses were documented for nine (39%) and 14 (61%) patients, respectively. Case-matched controls comprised patients treated with docetaxel-based PST without trastuzumab (D; n=23) or PST without docetaxel or trastuzumab (non-taxane, non-trastuzumab, NT-NT; n=23). All surgical specimens were blind-analysed by two independent pathologists, with immunohistochemical evaluation of B and T lymphocytes, macrophages, dendritic cells and natural killer (NK) cells. Potential cytolytic cells were stained for Granzyme B and TiA1. HER2 expression was also evaluated in residual tumour cells. Trastuzumab treatment was associated with significantly increased numbers of tumour-associated NK cells and increased lymphocyte expression of Granzyme B and TiA1 compared with controls. This study supports an in vivo role for immune (particularly NK cell) responses in the mechanism of trastuzumab action in breast cancer. These results suggest that trastuzumab plus taxanes lead to enhanced NK cell activity, which may partially account for the synergistic activity of trastuzumab and docetaxel in breast cancer.
authors.affiliation: Department of Pathology, Centre G-F Leclerc, Dijon 21000, France. larnould@dijon.fnclcc.fr
authors.forename: L
authors.initials: L
authors.lastname: Arnould
authors.forename: M
authors.initials: M
authors.lastname: Gelly
authors.forename: F
authors.initials: F
authors.lastname: Penault-Llorca
authors.forename: L
authors.initials: L
authors.lastname: Benoit
authors.forename: F
authors.initials: F
authors.lastname: Bonnetain
authors.forename: C
authors.initials: C
authors.lastname: Migeon
authors.forename: V
authors.initials: V
authors.lastname: Cabaret
authors.forename: V
authors.initials: V
authors.lastname: Fermeaux
authors.forename: P
authors.initials: P
authors.lastname: Bertheau
authors.forename: J
authors.initials: J
authors.lastname: Garnier
authors.forename: J-F
authors.initials: JF
authors.lastname: Jeannin
authors.forename: B
authors.initials: B
authors.lastname: Coudert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D003713:Dendritic Cells / Q000187:drug effects; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab