Male Breast Cancer: From Molecular Genetics to Clinical Management

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Apr 23

PMID 35454911

Authors

Matilde Pensabene

Claudia von Arx

Michelino De Laurentiis

Affiliations

Soon will be listed here.

Abstract

MBC is a rare disease accounting for almost 1% of all cancers in men and less than 1% of breast cancer. Emerging data on the genetic drivers of predisposition for MBC are available and different risk factors have been associated with its pathogenesis. Genetic alterations, such as pathogenetic variants in BRCA1/2 and other moderate-/low-penetrance genes, along with non-genetic risk factors, have been recognized as pathogenic factors for MBC. Preventive and therapeutic implications could be related to the detection of alterations in predisposing genes, especially BRCA1/2, and to the identification of oncogenic drivers different from FBC. However, approved treatments for MBC remain the same as FBC. Cancer genetic counseling has to be considered in the diagnostic work-up of MBC with or without positive oncological family history. Here, we review the literature, reporting recent data about this malignancy with a specific focus on epidemiology, and genetic and non-genetic risk factors. We introduce the perspective of cancer genetic counseling for MBC patients and their healthy at-risk family members, with a focus on different hereditary cancer syndromes.

Citing Articles

Global, Regional, and National Burden of Male Breast Cancer, 1990-2021: A Systematic Analysis for the Global Burden of Disease Study 2021.

Wang L, Wen P, Shao Q, Jiang D, Zhao Y, Zeng X Cancer Med. 2025; 14(3):e70632.

PMID: 39878368 PMC: 11775920. DOI: 10.1002/cam4.70632.

Male breast cancer: a 32-year retrospective analysis in radiation therapy referral center in northern Iran.

Asgharian M, Moslemi D, Nikbakht H, Jahani M, Bijani A, Mehdizadeh H Ann Med Surg (Lond). 2024; 86(10):5756-5761.

PMID: 39359768 PMC: 11444606. DOI: 10.1097/MS9.0000000000002571.

Pleomorphic/solid lobular carcinoma of male breast with PALB2 germline mutation: case report and literature review.

Rogges E, Corati T, Amato M, Campagna D, Farro J, De Toffol S Pathologica. 2024; 116(1):62-68.

PMID: 38482676 PMC: 10938273. DOI: 10.32074/1591-951X-936.

Gender-Specific Genetic Predisposition to Breast Cancer: Genes and Beyond.

Valentini V, Bucalo A, Conti G, Celli L, Porzio V, Capalbo C Cancers (Basel). 2024; 16(3).

PMID: 38339330 PMC: 10854694. DOI: 10.3390/cancers16030579.

Demographics, Characteristics, and Outcomes of Male Breast Cancer Patients at the Methodist Health System, Dallas, USA.

Nong H, Eastwood D, Rodriguez K, Puri V Cureus. 2023; 15(11):e49394.

PMID: 38146568 PMC: 10749682. DOI: 10.7759/cureus.49394.

References

Gentilini O, Chagas E, Zurrida S, Intra M, De Cicco C, Gatti G . Sentinel lymph node biopsy in male patients with early breast cancer. Oncologist. 2007; 12(5):512-5. DOI: 10.1634/theoncologist.12-5-512. View

Marroni F, Aretini P, DAndrea E, Caligo M, Cortesi L, Viel A . Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations. Eur J Hum Genet. 2004; 12(11):899-906. DOI: 10.1038/sj.ejhg.5201256. View

Li S, Silvestri V, Leslie G, Rebbeck T, Neuhausen S, Hopper J . Cancer Risks Associated With and Pathogenic Variants. J Clin Oncol. 2022; 40(14):1529-1541. PMC: 9084432. DOI: 10.1200/JCO.21.02112. View

BELL D, Varley J, Szydlo T, Kang D, Wahrer D, Shannon K . Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science. 2000; 286(5449):2528-31. DOI: 10.1126/science.286.5449.2528. View

Silvestri V, Rizzolo P, Zanna I, Falchetti M, Masala G, Bianchi S . PALB2 mutations in male breast cancer: a population-based study in Central Italy. Breast Cancer Res Treat. 2010; 122(1):299-301. DOI: 10.1007/s10549-010-0797-z. View

Riley B, Culver J, Skrzynia C, Senter L, Peters J, Costalas J . Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns. 2011; 21(2):151-61. DOI: 10.1007/s10897-011-9462-x. View

Ottini L, Silvestri V, Saieva C, Rizzolo P, Zanna I, Falchetti M . Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy. Breast Cancer Res Treat. 2013; 138(3):861-8. DOI: 10.1007/s10549-013-2459-4. View

Evans D, Susnerwala I, Dawson J, Woodward E, Maher E, Lalloo F . Risk of breast cancer in male BRCA2 carriers. J Med Genet. 2010; 47(10):710-1. DOI: 10.1136/jmg.2009.075176. View

Ding Y, Steele L, Kuan C, Greilac S, Neuhausen S . Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. Breast Cancer Res Treat. 2010; 126(3):771-8. PMC: 3059396. DOI: 10.1007/s10549-010-1195-2. View

10.

Song Y, Geng J, Liu T, Zhong Z, Liu Y, Xia B . Long CAG repeat sequence and protein expression of androgen receptor considered as prognostic indicators in male breast carcinoma. PLoS One. 2012; 7(12):e52271. PMC: 3522691. DOI: 10.1371/journal.pone.0052271. View

11.

Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R . Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet. 2006; 38(11):1239-41. DOI: 10.1038/ng1902. View

12.

Nicolosi P, Ledet E, Yang S, Michalski S, Freschi B, OLeary E . Prevalence of Germline Variants in Prostate Cancer and Implications for Current Genetic Testing Guidelines. JAMA Oncol. 2019; 5(4):523-528. PMC: 6459112. DOI: 10.1001/jamaoncol.2018.6760. View

13.

Biesma H, Schouten P, Lacle M, Sanders J, Brugman W, Kerkhoven R . Copy number profiling by array comparative genomic hybridization identifies frequently occurring BRCA2-like male breast cancer. Genes Chromosomes Cancer. 2015; 54(12):734-44. DOI: 10.1002/gcc.22284. View

14.

Maguire S, Perraki E, Tomczyk K, Jones M, Fletcher O, Pugh M . Common Susceptibility Loci for Male Breast Cancer. J Natl Cancer Inst. 2020; 113(4):453-461. PMC: 8023850. DOI: 10.1093/jnci/djaa101. View

15.

Vietri M, Caliendo G, Casamassimi A, Cioffi M, De Paola M, Napoli C . A novel PALB2 truncating mutation in an Italian family with male breast cancer. Oncol Rep. 2014; 33(3):1243-7. DOI: 10.3892/or.2014.3685. View

16.

Lopez M, Di Lauro L, Papaldo P, Lazzaro B . Chemotherapy in metastatic male breast cancer. Oncology. 1985; 42(4):205-9. DOI: 10.1159/000226032. View

17.

Humphries M, Sundara Rajan S, Honarpisheh H, Cserni G, Dent J, Fulford L . Characterisation of male breast cancer: a descriptive biomarker study from a large patient series. Sci Rep. 2017; 7:45293. PMC: 5368596. DOI: 10.1038/srep45293. View

18.

Deb S, Wong S, Li J, Do H, Weiss J, Byrne D . Mutational profiling of familial male breast cancers reveals similarities with luminal A female breast cancer with rare TP53 mutations. Br J Cancer. 2014; 111(12):2351-60. PMC: 4264438. DOI: 10.1038/bjc.2014.511. View

19.

Alter B, Rosenberg P, Brody L . Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. J Med Genet. 2006; 44(1):1-9. PMC: 2597904. DOI: 10.1136/jmg.2006.043257. View

20.

Ottini L, Silvestri V, Rizzolo P, Falchetti M, Zanna I, Saieva C . 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. 2012; 134(1):411-8. DOI: 10.1007/s10549-012-2062-0. View