title: Frequency of germline DNA genetic findings in an unselected prospective cohort of triple-negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial.
abstract: We describe the status and frequency of germline DNA genetic findings in an unselected prospective cohort of triple negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial. Study population includes 124 consecutive patients with stage II-III TNBC from a trial exploring the antitumor activity of neoadjuvant carboplatin/docetaxel chemotherapy enrolled between 2012 and March 2015, to determine the frequency of germline DNA genetic mutations. 17.1 % of the patients with germline DNA tested had deleterious mutations in any of the analyzed genes (12.38 % in BRCA1, 1.9 % in BRCA2 and BARD1 and 0.95 % in RAD51D). Attending the intrinsic subtype, all the BRCA1/2 carriers tested had basal-like subtype. Among wild-type (WT) patients, 70.11 % had basal subtype, 16.09 % HER2 enriched, 1.15 % Luminal B, and 4.60 % Normal-like. Mean age at diagnosis was significantly lower in mutation-carriers compared with no carriers (43.72 vs 53.10, p = 0.004). 3 BRCA1/2 carriers were detected between 51 and 60 years, and only one deleterious mutation (BARD1) over 60 years. A positive familiar history of breast and ovarian cancer was more frequent in patients with deleterious mutations (39.39 vs 17.94 %, p = 0.043). Our study confirms the prevalence of BRCA1/2 mutations in TNBC patients. TNBC should therefore be considered by itself as a criterion for BRCA1/2 genetic testing. Determination of other breast cancer predisposition genes implicated in homologous recombination should also be discussed in this population. However, no definitive conclusions can be reached due to the low prevalence and the uncertain clinical impact of most of the genes included.
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain. mgonzalez_rivera@yahoo.com.
authors.forename: Milagros
authors.initials: M
authors.lastname: González-Rivera
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain. m.lobodemena@gmail.com.
authors.forename: Miriam
authors.initials: M
authors.lastname: Lobo
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: López-Tarruella
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Jerez
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Del Monte-Millán
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Massarrah
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ramos-Medina
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ocaña
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Picornell
authors.affiliation: Medical Genetics Unit, Sistemas Genómicos SA, Valencia, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Santillán Garzón
authors.affiliation: Medical Genetics Unit, Sistemas Genómicos SA, Valencia, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Pérez-Carbornero
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: García-Saenz
authors.affiliation: Instituto Nacional de Enfermedades Neoplásicas (I.N.E.N.), Lima, Peru.
authors.forename: Henry
authors.initials: H
authors.lastname: Gómez
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Moreno
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Márquez-Rodas
authors.affiliation: Instituto Nacional de Enfermedades Neoplásicas (I.N.E.N.), Lima, Peru.
authors.forename: Hugo
authors.initials: H
authors.lastname: Fuentes
authors.affiliation: Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D016190:Carboplatin / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D011446:Prospective Studies; D043823:Taxoids / Q000627:therapeutic use; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D043823:Taxoids; D025521:Tumor Suppressor Proteins; D000077143:Docetaxel; D016190:Carboplatin; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: BRCA1; BRCA2; Carboplatin; Genes; Germline DNA; Triple-negative breast cancer