title: Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer.
abstract: Lapatinib enhances antibody-dependent cell-mediated cytotoxicity (ADCC) activity of trastuzumab. FcγR polymorphisms have been associated with both ADCC and clinical activity of trastuzumab in HER2+ breast cancer (BC) patients (pts). We analyzed FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms in the CHER-LOB trial population of HER2+ BCs treated with preoperative chemotherapy plus trastuzumab (arm A), lapatinib (arm B) or both (arm C). Genotyping was successfully performed in 73/121 (60%) pts. A significant improvement in pathological complete response (pCR) rate was observed for the combination arm C, but only in FcγRIIIa V allele carriers (C vs A, 67 vs 27%, P=0.043; C vs B, 67 vs 22%, P=0.012). An independent interaction between arm C and FcγRIIIa V allele was found for pCR (odds ratio=9.4; 95% confidence interval, 2.3-39.6; P=0.003). No significant associations were observed between pCR and FcγRIIa polymorphism, and between pre-treatment tumor-infiltrating lymphocytes and FcγR polymorphisms. Our study provides evidence for a FcγRIIIa V allele-restricted pCR benefit from neoadjuvant trastuzumab plus lapatinib in HER2+ BC.
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Musolino
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Naldi
authors.affiliation: Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
authors.forename: M V
authors.initials: MV
authors.lastname: Dieci
authors.affiliation: Department of Oncology, Guastalla Hospital, Guastalla, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Zanoni
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rimanti
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Boggiani
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Sgargi
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy.
authors.forename: D G
authors.initials: DG
authors.lastname: Generali
authors.affiliation: Medical Oncology Unit, Modena University Hospital, Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Piacentini
authors.affiliation: Medical Oncology Unit, Hospital of Piacenza, Piacenza, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ambroggi
authors.affiliation: Medical Oncology Unit, Ramazzini Hospital, Carpi, Italy.
authors.forename: K
authors.initials: K
authors.lastname: Cagossi
authors.affiliation: Medical Oncology Unit, Ospedale Infermi, Rimini, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Gianni
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sarti
authors.affiliation: Medical Oncology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bisagni
authors.affiliation: Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoni
authors.affiliation: Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
authors.forename: P F
authors.initials: PF
authors.lastname: Conte
authors.affiliation: Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Guarneri
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000077341:Lapatinib; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D017452:Receptors, IgG / Q000235:genetics*; D012189:Retrospective Studies; D013997:Time Factors; D000068878:Trastuzumab / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; D000068878:Trastuzumab; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; C508053:ERBB2 protein, human