title: Correlation of HER2, FCGR2A, and FCGR3A gene polymorphisms with trastuzumab related cardiac toxicity and efficacy in a subgroup of patients from UNICANCER-PACS 04 trial.
abstract: The purpose of this study was to investigate, in the context of a prospective node-positive-breast cancer trial HER2 containing-regimen (UNICANCER-PACS 04 trial), the predictive value of HER2, FCGRIIA, and FCGRIIIA gene polymorphisms for cardiac toxicity and efficacy of trastuzumab. We analyzed HER2-I655V, FCGR2A-H131R, and FCGR3A-V158F single nucleotide polymorphisms in patients in adjuvant setting treated by six courses of either fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2), or epirubicin 75 mg/m(2) and docetaxel 75 mg/m(2) every 3 weeks then randomly assigned, in case of HER2 overexpressing tumor, to either trastuzumab for 1 year or nothing. Left ventricular ejection fraction and clinical examination were monitored in each patient, seven times throughout the study to detect congestive heart failure or asymptomatic subclinical cardiac toxicity. All genotypes were analyzed in relation to cardiac toxicity, EFS, and OS. One hundred and thirty-two HER2-positive breast cancer patients were analyzed. The HER2-I655V genotype was significantly associated with cardiac toxicity (p = 0.025). The FCGR2A-131 H/H genotype was significantly correlated with a shorter EFS (p = 0.027). The FCGR3A-158 V/V genotype was not correlated with EFS nor OS. These results might be useful in making a treatment choice of HER2 blockers in adjuvant setting by with an increase in efficacy and decrease in toxicity.
authors.affiliation: ICM, Montpellier, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Roca
authors.forename: Véronique
authors.initials: V
authors.lastname: Diéras
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lappartient
authors.forename: Pierre
authors.initials: P
authors.lastname: Kerbrat
authors.forename: Laurent
authors.initials: L
authors.lastname: Cany
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chieze
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Canon
authors.forename: Marc
authors.initials: M
authors.lastname: Spielmann
authors.forename: Frédérique
authors.initials: F
authors.lastname: Penault-Llorca
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Martin
authors.forename: Christel
authors.initials: C
authors.lastname: Mesleard
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lemonnier
authors.forename: Patricia
authors.initials: P
authors.lastname: de Cremoux
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D000068878:Trastuzumab; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; D000068878:Trastuzumab; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; C508053:ERBB2 protein, human