FcγR2A and 3A polymorphisms predict clinical outcome of trastuzumab in both neoadjuvant and metastatic settings in patients with HER2-positive breast cancer.
BACKGROUND
Antibody-dependent-mediated cytotoxicity (ADCC) is one of the modes of action for trastuzumab. Recent data have suggested that fragment C γ receptor (FcγR) polymorphisms have an effect on ADCC. This prospective phase II trial aimed to evaluate whether these polymorphisms are associated with clinical efficacies in patients who received trastuzumab.


METHODS
Patients in a neoadjuvant (N) setting received Adriamycin and cyclophosphamide followed by weekly paclitaxel/trastuzumab. Patients in a metastatic (M) setting received single trastuzumab until progression. In total, 384 distinct single nucleotide polymorphisms of different FcγR, HER2, and fucosyltransferase loci were assessed.


RESULTS
Fifteen operable and 35 metastatic HER2-positive breast cancer patients were enrolled in each of the N and M settings, respectively. The FcγR2A-131 H/H genotype was significantly correlated with the pathologically documented response (pathological response) (P = 0.015) and the objective response (P = 0.043). The FcγR3A-158 V/V genotype was not correlated with the pathological response, but exhibited a tendency to be correlated with the objective response. Patients with the FcγR2A-131 H/H genotype had significantly longer progression-free survival in the M setting (P = 0.034).


CONCLUSIONS
The FcγR2A-131 H/H polymorphism predicted the pathological response to trastuzumab-based neoadjuvant chemotherapy in early-stage breast cancer, and the objective response to trastuzumab in metastatic breast cancer.
Departments of Breast and Medical Oncology. Electronic address: ketamura@ncc.go.jp.
K
K
Tamura
Departments of Breast and Medical Oncology.
C
C
Shimizu
Breast Surgery, National Cancer Center Hospital, Tokyo.
T
T
Hojo
Breast Surgery, National Cancer Center Hospital, Tokyo.
S
S
Akashi-Tanaka
Breast Surgery, National Cancer Center Hospital, Tokyo.
T
T
Kinoshita
Departments of Breast and Medical Oncology.
K
K
Yonemori
Departments of Breast and Medical Oncology.
T
T
Kouno
Departments of Breast and Medical Oncology.
N
N
Katsumata
Departments of Breast and Medical Oncology.
M
M
Ando
Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Ehime.
K
K
Aogi
Shien Lab, National Cancer Center Hospital, Tokyo.
F
F
Koizumi
Department of Genome Biology, Kinki University School of Medicine, Osaka, Japan.
K
K
Nishio
Departments of Breast and Medical Oncology.
Y
Y
Fujiwara
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D000068878:Trastuzumab; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; D000068878:Trastuzumab; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; C508053:ERBB2 protein, human