Abstract
Breast cancer occurs rarely in male patient. BRCA1 gene mutation seems to be related to male breast cancer, but its role is not clearly defined. We have identified in a male patient affected by breast cancer the BRCA1 gene variant p.P142H. We performed a literature research using the keywords “male breast cancer”, “male breast cancer mutations” and “BRCA” and we reviewed the cases. We found ew other studies regarding BRCA1 variant p.P142H, about female subjects. At the moment, BRCA1 gene variant p.P142H is not certainly classified as neutral or deleterious. Genetic testing for BRCA1 and BRCA2 and PALB2 mutation gene has been performed on our patient. Segregation analysis for this p.P142H BRCA1 variant has been extended to the second generation of the family. Genetic tests revealed a clear inheritance regarding the BRCA1 gene p. P142H variant. Of the eight patients with this specific genetic mutation, four presented breast cancer (bilateral in one case), two female and two male. None of the subjects in the family without the BRCA1 gene variant p. P142H presented breast cancer or other BRCA1 gene mutation-related cancers. Our analysis suggests that the BRCA1 gene variant p.P142H mutation is related with male breast cancer. Starting from these data, it can be inferred that more studies on MBC and its relation with the BRCA1 gene mutation P142H variant must be undertaken to improve prognostic and therapeutic strategies.
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Sousa B, Moser E, Cardoso F (2013) An update on male breast cancer and future directions for research and treatment. Eur J Pharmacol 717(1–3):71–83
Wasielewski M, den Bakker MA, van den Ouweland A et al (2009) CHEK2 1100delC and male breast cancer in the Netherlands. Breast Cancer Res Treat 116(2):397–400
Ohayon T, Gal I, Baruch RG et al (2004) CHEK2 1100delC and male breast cancer risk in Israel. Int J Cancer 108(3):479–480
Blanco A, de la Hoya M, Balmana J et al (2012) Detection of a large rearrangement in PALB2 in Spanish breast cancer families with male breast cancer. Breast Cancer Res Treat 132(1):307–315
Young IE, Kurian KM, Annik C et al (1999) A polymorphism in the CYP17 gene is associate with male breast cancer. Br J Cancer 81(1):141–143
Katri P, Hannele E, Jenni N, Szilvia S, Robert W (2008) Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families. BMC Cancer 8:146
Blay P, Santamaría I, Pitiot AS, Luque M, Alvarado MG, Lastra A et al (2013) Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain). BMC Cancer 13:243
Frank TS, Deffendaugh AM, Reid JE et al (2002) Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol 20:1480–1490
Hyo JK, Young BH, Yong WY, Chi-Heum C, Antai W, Insoo B (2013) The correlations between BRCA1 defect and environmental factors in the risk of breast cancer. J Toxicol Sci 38(3):355–361
Bielinska B, Gaj P, Kluska A, Nowakowska D, Balabas A et al (2013) Association of the BRCA1 promoter polymorphism rs11655505 with the risk of familial breast and/or ovarian cancer. Fam Cancer 12(4):691–698
Chenevix-Trench G, Healey S, Lakhani S et al (2006) Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. Cancer Res 66(4):2019–2027
Easton DF, Deffenbaugh AM, Pruss D et al (2007) A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet 81(5):873–883
Judkins T, Hendrickson BC, Deffenbaugh AM (2005) Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. Cancer Res 65(21):10096–10103
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249
Hodgson NC, Button JH, Franceschi D et al (2004) Male breast cancer: is the incidence increasing? Ann Surg Oncol 11(8):751–755
Speirs V, Shaaban AM (2009) The rising incidence of male breast cancer. Breast Cancer Res Treat 115(2):429–430
White J, Kearins O, Dodwell D et al (2011) Male breast carcinoma: increased awareness needed. Breast Cancer Res 13(5):219
Ruddy KJ, Winer EP (2013) Male Breast Cancer: risk factors, biology, diagnosis, treatment, and survivorship. Ann Oncol 24(6):1434–1443
Fentiman IS, Fourquet A, Hortobagyi GN (2006) Male breast cancer. Lancet 367:595–604
Falchetti M, Lupi R, Rizzolo P et al (2008) BRCA1/BRCA2 rearragements and CHEK 2 common mutations are infrequent in Italian male breast cancer cases. Breast Cancer Res Treat 110(1):161–167
Ottini L, Silvestri V, Rizzolo P, Falchetti M, Zanna I, Saieva C, Masala G, Bianchi S, Manoukian S, Barile M et al (2012) Clinical and pathologic characteristics of BRCA-positive and BRCA-negative male breast cancer patients: results from a collaborative multicenter study in Italy. Breast Cancer Res Treat 134(1):411–418
Deb S, Do H, Byrne D, Jene N, kConFab Investigators, Dobrovic A, Fox SB (2013) PIK3CA mutations are frequently observed in BRCAX but not BRCA2-associated male breast cancer. Breast Cancer Res 15:69
Tai YC, Domchek S, Parmigiani G, Chen S (2007) Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 99(23):1811–1814
Kwiatkowska E, Teresiak M, Filas V et al (2003) BRCA2 mutations and androgen receptor expression as independent predictors of outcome of male breast cancer patients. Clin Cancer Res 9:4452–4459
Young-Ho L, Ching-Ying K, Jeremy MS, David KA et al (2013) HP1 promotes tumor suppressor BRCA1 functions during the DNA damage response. Nucleic Acids Res 41(11):5784–5798
Li M, Yu X (2013) Function of BRCA1 in the DNA damage response is mediated by ADP-ribosylation. Cancer Cell 23(5):693–704
De Luca P, Moiola CP, Zalazar F, Gardner K, Vazquez ES (2013) BRCA1 and p53 regulate critical prostate cancer pathways. Prostate Cancer Prostatic Dis 16(3):233–238
Levy-Lahad E, Friedman E (2007) Cancer risks among BRCA1 and BRCA2 mutation carriers. Br J Cancer 96(1):11–15
Han SA, Park SK, Ahn SH et al (2011) The Korean Hereditary Breast Cancer (KOHBRA) Study: protocols and Interim Report. Clinical Oncology 23(7):434–441
Fiala L, Coufal O, Fait V, Foretová L (2010) Male breast cancer–our experience. Rozhl Chir 89(10):612–618
Varesco L, Viassolo V, Viel A et al (2013) Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: a retrospective study in a sample of Italian cancer genetics clinics. The Breast 22(6):1130–1135
Kast K, Schmutzler RK, Rhiem K et al (2014) Validation of the Manchester scoring system for predicting BRCA1/2 mutations in 9,390 families suspected of having hereditary breast and ovarian cancer. Int J Cancer. doi:10.1002/ijc.28875
Millot GA, Carvalho MA, Caputo SM et al (2012) A guide for functional analysis of BRCA1 variants of uncertain significance. Hum Mutat 33(11):1526–1537
Wei L, Lan L, Hong Z et al (2008) Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80. Mol Cell Biol 24:7380–7393
Towler WI, Zhang J, Ransburgh DJ et al (2013) Analysis of BRCA1 variants in double-strand break repair by homologous recombination and single-strand annealing. Hum Mutat 34(3):439–445
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Spinelli, C., Strambi, S., Piccini, L. et al. BRCA1 gene variant p.P142H associated with male breast cancer: a two-generation genealogic study and literature review. Familial Cancer 14, 515–519 (2015). https://doi.org/10.1007/s10689-015-9819-7
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DOI: https://doi.org/10.1007/s10689-015-9819-7