BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study

Autores de IIS La Fe

• Inmaculada De Juan Jiménez

  Autor

• Sarai Palanca Suela

  Autor

• Ángel Agustín Segura Huerta

  Autor

• Isabel Chirivella Gonzalez

  Autor

• Isabel Tena Garcia

  Autor

• Maria Zaida Garcia Casado

  Autor

• Rosa María Murria Estal

  Autor

• Marta Llop García

  Autor

• Eva Barragán González

  Autor

• Pascual Bolufer Gilabert

  Autor

Participantes ajenos a IIS La Fe

• Domenech A
• Feliubadaló L
• Osorio A
• de la Hoya M
• Sánchez AB
• Infante M
• Díez O
• Vega A
• Teulé À
• Barroso A
• Pérez P
• Durán M
• Carrasco E
• Juan-Fita MJ
• Izquierdo Á
• Benítez J
• Caldés T
• Salas D

Grupos

• Hematología y Hemoterapia

  

  Investigador Principal

  Javier De La Rubia Comos

• Investigación Clínica y Traslacional en Cáncer

  

  Leader

  José Gómez Codina

Abstract

Male breast cancer (MBC) is a rare disease that represents < 1 % of all breast cancers (BCs). We analyze the results of a multicenter study performed in Spanish familial MBC including family history of hereditary breast and ovarian cancer syndrome (HBOCS) and clinicopathological features. We also study the relationship between BRCA1/BRCA2 mutational status in male relatives affected with cancer (MAC) and, family history and tumor types. The study included 312 men index cases with family history of HBOCS and 61 MAC BRCA1/2 mutation-carriers. Family history, histological grade (HG), clinicopathological and immunohistochemistry data were collected. BRCA1/2 mutation analyses were performed by direct sequencing or screening methods and the large rearrangements by multiplex ligation dependent probe amplification. We found 49 mutation-carriers (15.7 %), 95.9 % with BRCA2 mutations. BRCA2 mutation-carriers were associated with families with at least one MBC and one BC in female (type II; p = 0.05). Strong association were found between the presence of pathogenic mutations in MBCs and the advanced HG (p = 0.003). c.658_659delTG, c.2808_2811delACAA, c.6275_6276delTT and c.9026_9030delATCAT were the most prevalent mutations. In 61 MAC we found 20 mutations in BRCA1 and 41 in BRCA2. For MAC we show that mutational status was differentially associated with family history (p = 0.018) and tumor type, being BRCA2 mutations linked with BC and prostatic cancer (p = 0.018). MBC caused by BRCA1/2 mutations define two types of MBCs. The most frequent caused by BRCA2 mutation linked to type II families and the rarest one attributed to BRCA1 mutation. Tumor associated with MAC suggest that only BRCA2 mutations have to do with a specific type of cancer (BC and prostatic cancer); but the linkage to tumors is questionable for BRCA1 mutations .

Keywords

• Familial male breast cancer; Hereditary breast and ovarian cancer syndrome; BRCA1; BRCA2 mutations