Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

Male breast cancer

Written2016-12Cathy B Moelans, Petra van der Groep, Paul J van Diest
Department of Pathology, University Medical Center Utrecht, Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA, Utrecht, The Netherlands / cmoelans@umcutrecht.nl, p.vandergroep@umcutrecht.nl and p.j.vandiest@umcutrecht.nl

(Note : for Links provided by Atlas : click)

Abstract

Abstract Review on Male breast cancer, with data on clinics, and the genes involved.

Identity

ICD-Topo C500-C506,C508-C509
ICD-Morpho 8500/3
ICD-Morpho 8200/3
ICD-Morpho 8401/3
ICD-Morpho 8507/2
ICD-Morpho 8480/3
ICD-Morpho 8503/3
ICD-Morpho 8502/3
ICD-Morpho 8500/2
ICD-Morpho 8520/3
ICD-Morpho 8520/2
Atlas_Id 6242
Phylum Female organs: Breast::carcinoma
Other namesBreast Neoplasms, Male
Breast Carcinoma, Male

Classification

Note Male breast cancer (MBC) is extremely rare and accounts for less than 1% of all (Anderson et al., 2010). Only 0.2% of all cancer types in men is a breast cancer (in women, this is 31%). The annual incidence is 1/100.000 men (Ly et al., 2013).
While thought traditionally to be similar to post-menopausal female breast cancer (FBC), emerging evidence suggests that MBC may be different, with unique molecular subtypes (Johansson et al., 2014). Two distinct subgroups of MBC, luminal M1 and luminal M2, have been identified which differ from the well-established intrinsic subtypes of breast cancer in women. These novel subgroups appear unique to MBC, with the luminal M2 subgroup demonstrating higher immune response and ER signaling, and luminal M1 tumors displaying more tumor invasion and metastasis, proliferation and HER2 signaling. MBCs of the luminal M1 subgroup display more aggressive features than other MBC tumors.
The frequency of histological subtypes (per WHO 2012) differs between males and females, with invasive carcinomas of no special type ( ) being by far the most common subtype (> 90%) (Deb et al., 2016). This is followed by and which, proportionately, are seen more frequently in males when compared to females. Conversely, in men, are less common and represent only 1% of all male breast cancers. Other less common carcinoma subtypes seen in males also include , , and . The majority of MBC present as symptomatic invasive disease. The early detection of the pre-invasive form, (DCIS), is rare in the absence of effective breast screening in men (Anderson and Devesa, 2005). (LCIS) has been described mostly coexisting with invasive lobular carcinoma.
MBCs more frequently express estrogen receptor (ER) and progesterone receptor (PR) than FBCs (ER > 90 versus 76%, PR > 75 versus 60% in FBC). HER2 amplification and overexpression is less frequent in males when compared to females (Deb et al., 2016). Preliminary results from 1483 MBC cases amassed by EORTC10085, TBCRC, BIG and the NABCG International Male Breast Cancer Program were reported by Cardoso et al. in 2014 (Cardoso et al., 2014). Of the tumors analysed, 92% were ER+, 35% PR+, and only 5% HER2+. Subsequently, the most common phenotype seen in MBC is the luminal-like (ER+ and/or PR+, HER2-) subtype with only occasional HER2-driven (ER- and PR- ,HER2+) and basal-like subtypes [ER-, PR-, HER2-]. Within the luminal-like subtype, there appears to be an overrepresentation of the luminal B-like category (Ki67 high) versus the luminal A-like category (Ki67 low), compared to FBC (Piscuoglio et al., 2016; Kornegoor et al., 2012a).

Clinics and Pathology

Disease MBC is usually discovered (75%) as a painless retroareolar mass. Other presenting features include nipple retraction (9%), nipple discharge (6%), ulceration (6%) and pain (5%)(Fentiman, 2009).The rarity of MBC usually results in a delay of recognition and diagnosis. Consequently, MBC is often diagnosed at older age and with a more advanced clinical stage compared to FBC (more than 40% have stage III or IV disease) (Fentiman et al., 2006). Male and female patients with breast cancer are staged similarly according to the American Joint committee on Cancer (AJCC) or Union for International Cancer Control (UICC) guidelines.
Etiology The current literature suggests that genetic factors including BRCA2 mutations, family history, age, androgen/estrogen imbalance, and environmental exposures may predispose to male breast cancer (Ferzoco and Ruddy, 2016). Like many cancers, MBC is an age-related malignancy, with incidence peaking in the mid-60s. Men diagnosed with breast cancer tend to be 5-10 years older than women diagnosed with breast cancer. Those with a family history of breast cancer have two to three times the risk of developing breast cancer themselves. This risk increases when multiple family members are affected. About 20 % of men with breast cancer have at least one first-degree female relative with breast cancer. BRCA1/2 mutations, and specifically BRCA2 mutations, are a clear causal factor for MBC. Multiple population-based studies have shown that 4-15 % of men with breast cancer carry deleterious BRCA2 mutations and less than 5 % carry a BRCA1 mutation (Ferzoco and Ruddy, 2016). Mutations in CHEK2 may confer an increased risk of MBC too, although the relative risk of these mutations, particularly CHEK2*1100delC, are uncertain (Neuhausen et al., 2004). Mutations within the DNA binding domain of androgen receptor have been described in MBC patients and there is a link between the cytochrome p540c17α enzyme (CYP17A1) and MBC. See section Genetics for more gene aberration specific information.
Hormonal imbalance, in particularly the excess of estrogen and a deficiency of testosterone, can confer heightened risk for the development of MBC. This imbalance can be caused by testicular abnormalities, liver diseases/cirrhosis and obesity. Furthermore, having Klinefelter's syndrome (characterized by one or more additional X chromosomes, testicular dysgenesis, gynecomastia, low testosterone concentrations and increased gonadotrophins) is strongly associated with MBC, with a 20-50 times higher risk compared to the general male population (Hultborn et al., 1997). Gynecomastia on the other hand, caused by an imbalance in estrogen and androgen levels, is not a risk factor for MBC (Ewertz et al., 2001; Krause, 2004). Interfering with estrogen or androgen levels by administration of estrogen or anti-androgens to trans-sexuals and for treatment of prostate cancer have been implicated as causative factors in MBC (Ganly and Taylor, 1995; Karamanakos et al., 2004; Gooren et al., 2013).
Radiation exposure increases risk of breast cancer in both women and men. Small numbers of chest X-rays do not, but prolonged exposure to radiographs or radiotherapy may be harmful (Fentiman, 2009). Environmental exposures including electromagnetic radiation, heat, polycyclic aromatic hydrocarbons, alcohol, and red meat have been studied in relation to male breast cancer, but none have convincingly found to be associated with incidence across studies (Ottini et al., 2010).
Epidemiology In Western countries MBC comprises less than 1 % of all cancers in men. Worldwide variation of MBC resembles that of FBC with higher incidences in North America and Europe and lower incidences in Asia (Ottini et al., 2010). A substantial higher rate of MBC cases has been reported in Africa. The incidence rates of MBC in Uganda and Zambia for example are 5% and 15%, respectively (Bhagwandeen, 1972; Ojara, 1978). Similar to FBC, MBC incidence in Japan is significantly lower than the average (IARC, 1976). Recent epidemiological studies indicate that MBC incidence is rising (Giordano et al., 2004; Stang and Thomssen, 2008; Speirs and Shaaban, 2009).
The incidence and mortality of MBC increase with age. The bimodal age distribution seen in FBC patients is absent in MBC patients. Median age at diagnosis is 68.5 years with 5% of patients diagnosed with distant metastases (M1). Of patients presenting without distant metastases (M0), 60% are lymph node negative and 51% have T1 tumors at diagnosis (tumor size 2 centimeters or less) (Cardoso et al., 2014). Breast cancer mortality and survival rates have improved significantly over time for both MBC and FBC, but progress for men has lagged behind that for women (Anderson et al., 2010). Overall survival, especially 5-year overall survival, is lower compared to female patients because of the older age at diagnosis and more advanced stage at presentation (Giordano et al., 2004). Disease specific survival rates are higher than overall survival rates due to older average age and deaths from other comorbid diseases (Giordano, 2005).
Pathology The Pathologist assesses resection margins, lymph node status, tumor size, tumor grade, mitotic activity, histological subtype, lymphovascular invasion, hormonal receptor status (by immunohistochemistry) and HER2 status. As already mentioned in the section "Classification", the majority of MBC are invasive ductal carcinomas (of no special type) (> 90%) (Deb et al., 2016). Lobular carcinomas are less common and represent only 1-2% of all MBCs. MBCs more frequently express ER and PR than FBC (ER > 90% versus 76%, PR > 75% versus 60% in FBC). HER2 amplification and overexpression is less frequent in males (5%) compared to females (10-15%) (Cardoso et al., 2014; Deb et al., 2016). Subsequently, the most common phenotype seen in MBC is the luminal-like (>95%; ER+ and/or PR+, HER2-) subtype with only occasional HER2-driven-like (ER- and PR-, HER2+) and basal-like (triple negative) subtypes [ER-, PR-, HER2-]. Within the luminal-like subtype, MBC are more frequently luminal B-like (Ki67 high) compared to FBC (Piscuoglio et al., 2016; Kornegoor et al., 2012a). Fibrotic focus is seen in 25% of MBC and correlated to hypoxia-inducible factor-1α overexpression (Kornegoor et al., 2012b).
Although rare, DCIS and LCIS are recognised precursor lesions, as in the female breast. In contrast to females, columnar cell lesions, recognized precursor lesions of low grade lesions in the female breast, seem to be very rare in the male breast (Verschuur-Maes et al., 2014).
 
Invasive micropapillary male breast cancer, a common histotype in the male breast.
 
Solid pattern of invasive ductal male breast cancer, a common histotype in the male breast.
 
Invasive lobular male breast cancer, a rare histotype in the male breast.
 
Adenoid cystic male breast cancer, a rare histotype in the male breast.
Treatment As MBC is rare, there are few clinical trials specifically focused on gender-orientated treatment; many clinical recommendations in MBC are therefore derived from studies performed in female breast cancer. Surgery is the first choice of treatment and most men undergo modified radical mastectomy with axillary lymph node dissection or sentinel node biopsy (Giordano, 2005). This is primarily due to a paucity of breast tissue in men as well as the fact that male BC usually occurs in central locations. Post-surgical radiation criteria are extrapolated from female breast cancer studies. Although postoperative radiation is often routinely utilized in all stages of male breast cancer to help decrease the risk of local recurrence, this risk is believed to be small, especially in early stage disease (3% in stage 1/2).Men with tumors ≥ 5 cm, T4 and lymph node positive disease are therefore more likely to receive post-surgery radiation (Chakravarthy and Kim, 2002).
Adjuvant endocrine therapy is standard treatment in MBC patients because the majority is hormone receptor positive. Many retrospective series have evaluated the effectiveness of tamoxifen (Nolvadex®; AstraZeneca Pharmaceuticals, http://www.astrazeneca-us.com) in MBC, showing a reduced risk of breast cancer recurrence and death in the metastatic and adjuvant setting. The role of aromatase inhibitors in the adjuvant setting for male patients is limited (Giordano, 2005) and their use as monotherapy or in combination with gonadotropin-releasing hormone (GnRH) analogues is largely restricted to the metastatic stage of the disease (Zagouri et al., 2015)
Given the established benefit of chemotherapy in women and the limited suggestive evidence in men, most clinicians use similar guidelines for adjuvant chemotherapy in male and female patients (Giordano, 2005).
Prognosis The 5-year and 10-year relative survival rate for men with breast cancer is 84 and 72 percent, respectively (Howlader et al., 2016). Tumor stage is determined using the American Joint Committee on Cancer classification system, which considers tumor size, nodal involvement, and distant metastases. More than 40% of men with breast cancer present with stage 3/4 disease and therefore men have a worse overall survival but similar disease specific survival compared to women (Giordano, 2005). When MBC is diagnosed early, preferable when only DCIS is present, the tumors are mostly low to intermediate grade and the occurrence of distant metastasis is very unlikely (Ruddy and Winer, 2013).
Prognostic factors that have been evaluated include the size of the lesion, mitotic index, tumor grade, lymph node status and molecular type, all of which correlate well with prognosis (Giordano et al., 2004; Ruddy and Winer, 2013; Kornegoor et al., 2012a). Based on numbers from 2009, node negative MBC have a five-year survival rate of 90%, compared with 65% five-year survival rate for node positive MBC (Fentiman, 2009). Also, grade 1 patients have a five-year survival of 76%, dropping to 65% for those with grade 2 tumours and 43% for grade 3 MBC (Fentiman, 2009). In more recent studies, ER negativity (Ruddy and Winer, 2013; Abreu et al., 2016), fibrotic focus >8 mm, hypoxia-inducible factor-1α overexpression and nuclear area (Kornegoor et al., 2012a; Veta et al., 2012) appear to be prognostic factors in MBC too. There is no or little evidence of a correlation between HER2, Ki67, PR or lymphovascular invasion and prognosis (Ruddy and Winer, 2013).
Prognostic models that have been developed for FBC like the Multivariate Prognostic Index (consisting of mitotic index, tumour size and lymph node status), Nottingham Prognostic Index (consisting of grade, tumour size and lymph node status), Adjuvant! and Predict seem to perform quite well for MBC patients too (van der Pol et al., 2016). The combination of Bcl2 expression and mitotic index on the other hand, as opposed to FBC does not predict survival in MBC (Lacle et al., 2013).
Interestingly, a multicenter international study that pooled data from 13 cancer registries found that 12.5% of 3409 MBC survivors went on to develop a different (non-breast) cancer, and that risk of new primary cancers was elevated in the small intestine, rectum, pancreas, skin (non-melanoma), prostate, and lymphatics/blood. Other more recent studies have confirmed an elevated risk for other cancers in MBC survivors (Ruddy and Winer, 2013).

Genetics

Note The majority of MBC cases are sporadic, with many different oncogenes and tumor suppressor genes involved, while 10% are estimated to be due to an inherited predisposition (Rizzolo et al., 2013). In comparison with FBC there is a larger proportion of BRCA2 germline mutation carriers, (occurring in 10% of MBC), and underrepresentation of BRCA1 germline mutation carriers (found in only 1%). PALB2 and CHEK2 mutations have been reported in families with MBC. The contribution of BRIP1 and RAD51C mutations to breast cancer predisposition in males seems to moderate compared with CHEK2 and PALB2. The androgen receptor (AR) gene and the cytochrome p540c17α gene (CYP17) have been suggested to play a role in MBC predisposition but these results were not supported by additional studies. Lastly, besides in Klinefelter syndrome patients, MBC have been reported rarely in Li-Fraumeni, Cowden and Lynch syndrome patients (Deb et al., 2016).
HYPERMETHYLATION
Promoter hypermethylation is common in MBC and high methylation status correlates with aggressive phenotype and poor survival. ESR1 and GSTP1 promoter hypermethylation seem to be involved in development and/or progression of high-grade MBC. Although FBC and MBC share a set of commonly methylated genes, many of the studied genes are less frequently methylated in male breast cancer, pointing towards possible differences between male and female breast carcinogenesis (Kornegoor et al., 2012d). Unsupervised clustering of the most variable CpGs among MBC revealed two stable epitypes, designated ME1 and ME2, closely associated with the transcriptional subgroups luminal M1 and M2 (see "Classification"). Tumors in the ME1 group were more proliferative and aggressive than ME2 tumors, and showed a tendency toward inferior survival. ME1 tumors also displayed hypermethylation of PRC2 (polycomb) target genes and high expression of EZH2, one of the core components of PRC2. Differential methylation patterns were not only seen between the MBC epitypes, but also between MBCs and FBCs that cluster together (Johansson et al., 2015).

Cytogenetics

Cytogenetics Molecular Cytogenetic data in MBC are largely based on comparative genomic hybridization (CGH) studies preceded by a handful of small-scale karyotyping and microsatellite marker studies (Mitchell, 1990; Gudmundsson et al., 1995; Wingren et al., 1997; Rudas et al., 2000). Genomic gains are more common in MBC than in FBC and often involve whole chromosome arms, while losses of genomic material are less frequent (Tommasi et al., 2010; Johansson et al., 2011). The most common aberrations are similar between the genders, but high-level amplifications are more common in FBC (Johansson et al., 2011). Chromosomal gains are most frequent at 1q (~50%), 8q (~50%), 11q (~40%), 16p (~40%), 17q (~40%), 20q (~30%), 7q (~20%) and Xp (~20%). Losses are most commonly observed at 8p (~40%), 11q (~40%), 13q (~30%), 16q (~30%), 17p (~30%),1p (~20%) and 22q (20%) (Rudlowski et al., 2006; Tommasi et al., 2010; Johansson et al., 2011; Piscuoglio et al., 2016). Gains at 16p, 20q and Xq and losses at 13q correlate significantly with a higher degree of cytogenetic complexity (Rudlowski et al., 2006). In MBC chromosome 17 shows less complex rearrangements and fewer copy number changes compared to FBC. Frequent gains of 17q, encompassing two distinct amplicons, and losses of 17p were observed, but no whole chromosome 17 polyploidies (Lacle et al., 2015). Copy number loss on 16q is less frequent in MBC than FBC and, in combination with 16p gain, identifies a group of MBC with low propensity to develop lymph node metastases (Lacle et al., 2013).
Using fluorescence in situ hybridization (FISH) and multiplex ligation dependent probe amplification (MLPA), gain or amplification of ERBB2, MYC, CCDN1, TRAF4, CDC6 and MTDH have been described in MBC (Bloom et al., 2001; Bärlund et al., 2004; Rudlowski et al., 2004; Kornegoor et al., 2012c; Schildhaus et al., 2013). Using next generation sequencing, high-level amplifications of 8p11.23 (14%, including FGFR1 and ZNF703), 8q24.21 (17%, encompassing MYC), 17q23.2 (3%, including PPM1D), and 20q13.2 (3%, encompassing AURKA) were observed, as were homozygous deletions in CDKN2A (2%) and ATM (2%)(Piscuoglio et al., 2016).
Translocations have not been systematically studied in MBC. One of the best known translocations in a specific subtype of female breast cancer (secretory type), a recurrent chromosomal translocation t(12;15)(p13;q25) leading to the formation of the ETV6 / NTRK3 fusion gene has been described in secretory MBC as well (Arce et al., 2005). To our knowledge, only nine previous articles deal with adenoid cystic carcinoma (ACC) in the male breast but none of these studies have reported on the well-known recurrent translocation t(6;9)(q22-23;p23-24) in FBC, resulting in a fusion of the two transcription factor genes MYB and NFIB (Persson et al., 2009; Tang et al., 2015).

Genes involved and Proteins

Note The number of genetic alterations in (male) breast cancer is immense and it is therefore not possible to elaborate on all of them. A selection was made based on the aberration frequency and the amount of evidence/literature present. Several of the genes/proteins involved in MBC have already been described in female "Breast: Ductal carcinoma". These will not be repeated here (HER2/ERBB2, FGFR1, BRCA1, PTEN, ATM and CDH1).
Gene Name BRCA2
Location 13q22
Dna / Rna The BRCA2 gene is composed of 27 exons. The structure and function of BRCA2 have extensively been described elsewhere (http://atlasgeneticsoncology.org/Genes/BRCA2ID164ch13q13.html) and will therefore not be repeated here.
Protein Multiple population-based studies have shown that 4-15 % of men with breast cancer carry deleterious BRCA2 mutations (Ferzoco and Ruddy, 2016). By the age of 80 years, the cumulative risk of breast cancer in male BRCA2 germline mutation carriers has been estimated at 7% (Thompson et al., 2001). Among men with a family history of breast and/or ovarian cancer, reported mutation frequencies are generally higher. In the largest study so far comprising 642 families with MBC (these families had at least one additional case of FBC or ovarian cancer), BRCA1/2 mutation prevalence was 35.8% (95% CI: 32.2% to 39.6%) for MBC with at least one FBC or ovarian cancer in the family. BRCA2 mutations were found more frequently (13-65%) than BRCA1 mutations (3-9%) in families without occurrence of ovarian carcinoma. In cases where additional ovarian carcinoma cases were present in the family, a similar prevalence of mutations was found in BRCA1 (23-27%) and BRCA2 (27-30%)(Kast et al., 2016). In addition, there are populations who carry founder mutations that are significantly more common. For example, the BRCA2 999del5 founder mutation is implicated in over 40 % of Icelandic MBC cases (Thorlacius et al., 1996). This mutation, a 5 bp deletion in exon 9 starting at nucleotide 999, leads to a stop codon at nucleotide 1047 and to premature truncation of protein translation. Among BRCA2 MBCs, grade significantly decreases with increasing age at diagnosis. Compared with BRCA2 FBCs, BRCA2 MBCs are of significantly higher stage and higher grade (Silvestri et al., 2016).

Gene Name PALB2
Location 16p12.2
Protein PALB2 (partner and localizer of BRCA2) plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks. The 1,186-amino acid protein has a calculated molecular mass of about 130 kD, contains an N-terminal coiled coil domain and a C-terminal WD40 repeat domain that interacts with BRCA2 and RAD51. Inherited heterozygosity for this gene has been associated with an increased risk of breast cancer. Additionally, biallelic mutations of PALB2 have been linked to Fanconi anemia, which also has an increased risk of developing malignant disease.
PALB2 mutations have been found in families with both FBC and MBC, suggesting that this gene may be involved in MBC risk (Rahman et al., 2007; Garcèa et al., 2009). Moreover, PALB2 heterozygotes are 4-fold more likely to have a male relative with breast cancer (Casadei et al., 2011). Based on a handful of studies, PALB2 may have a role as moderate-penetrance gene in MBC at a comparable extent as for female breast cancer (Rizzolo et al., 2013). A recent study added strength to this evidence by performing whole exome sequencing in germline DNA of 1 male and 2 female BRCA1/2 mutation-negative breast cancer cases from a pedigree showing a first-degree family history of MBC and targeted PALB2 sequencing in 48 high-risk, BRCA1/2 mutation-negative MBC cases (Silvestri et al., 2016). According to this largest study so far, the frequency of PALB2 pathogenic mutations in high-risk MBC cases is higher than that observed in high-risk FBC cases (ie, 4% vs 1%).

Gene Name CHEK2
Location 22q12.1
Protein The protein encoded by checkpoint kinase 2 (CHEK2) is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein TP53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in CHEK2 are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene.
It has been estimated that the CHEK2 1100delC mutation accounts for 9% of MBC cases and confers about 10-fold increase of breast cancer risk in men lacking BRCA1 and BRCA2 mutations (Meijers-Heijboer et al., 2002). Other studies have reported lower CHEK2 mutation frequencies in MBC, ranging from 2% to 4% (Sodha et al., 2004; Syrjäkoski et al., 2004; Wasielewski et al., 2009).

Gene Name AR
Location Xq12
Protein The androgen receptor (AR) gene is more than 90 kb long and encodes a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates to the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Two alternatively spliced variants encoding distinct isoforms have been described.
Androgen hyposensitivity caused by either AR mutations or long CAG repeats might be a causal factor for MBC (Di Lauro et al., 2015). Mutations in the AR gene have been described in MBC and were shown to be associated with complete androgen insensitivity (CAIS) (Wooster et al., 1992; Lobaccaro et al., 1993). Also, variations of the polyglutamine (CAG) repeat within exon 1 of AR were demonstrated in MBC, with shorter CAG tracts associated with increased AR transcriptional activity, and longer CAG tracts resulting in a suboptimal ligand-mediated stimulation of AR (Young et al., 2000; Song et al., 2012). Immunohistochemistry studies of MBC samples reported AR expression in a range of 34-95% (Di Lauro et al., 2015). In addition to this striking variability, controversy exists, and conflicting data were reported, on the association between AR expression and disease stage and/or survival outcomes.

Gene Name CYP17A1
Location 10q24.3
Protein This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia.
A polymorphic T to C substitution has been described that creates an additional CCACC type promoter site 34 bp upstream from the site of initiation of translation (Carey et al., 1994). It is thought that the additional promoter site may increase the rate of transcription of the gene and thereby increase enzyme activity. Serum oestradiol levels are higher in women hetero- and homozygous for the C allele of the CYP17 gene (Feigelson et al., 1998). A germline T to C variant in CYP17 has been associated with an increased male breast cancer risk (Young et al., 1999) with an odds ratio (OR) of 2.10 (95% confidence interval 1.04-4.27). A subsequent study, however, did not observe a significant association between MBC risk and CYP17 genotype, but the frequency of the CC genotype was higher among carriers of the BRCA2 999del5 Icelandic founder mutation (33.3%) than non-carriers (16.7%; Gudmundsdottir et al., 2003).

Gene Name PIK3CA
Location 3q26.3
Protein The PIK3CA gene is composed of 21 exons, 20 of them coding exons, and encodes a cytoplasmic protein of 1,068 amino acid residues. The PIK3CA gene encodes the p110alpha protein which is a catalytic subunit of the class I PI 3-kinases (PI3K). Class I PI3K are heterodimeric molecules composed of a p110 catalytic subunit and a regulatory subunit. PI 3-Kinases (phosphoinositide 3-kinases, PI3Ks) coordinate a diverse range of cell functions including proliferation, cell survival, degranulation, vesicular trafficking and cell migration.
PIK3CA activating mutations show a high prevalence in female breast cancer (40.1% coding mutations in METABRIC)(Pereira et al., 2016) and are associated with higher age at diagnosis, hormone receptor positivity, HER2 negativity, lower tumor grade and stage, and lymph node negativity. PIK3CA mutations have been associated with significantly longer metastasis-free survival, especially in the PR-positive and HER2-positive subgroups (Cizkova et al., 2012), may have independent driver properties in a HER2-positive context, and have been implicated in resistance to anti-HER2 therapies (Nahta and Esteva, 2006). The majority of mutations occur at three hotspots (E542, E545, or H1047), making these ideal targets for therapeutic development. MBC less frequently harbor PIK3CA mutations (20%) than ER-positive/HER2-negative FBC but nevertheless it is the most frequently mutated gene in MBC. Almost all reported PIK3CA mutations in MBC affected the hotspots (Piscuoglio et al., 2016).

Gene Name GATA3
Location 10p15
Protein The GATA3 gene contains 6 exons. The full length GATA3 protein contains either 443 amino acids (isoform a) or 444 amino acids (isoform b), corresponding to molecular weights of 47,9 kDa and 48,0 kDa respectively. The GATA3 protein contains two zinc finger motifs as well as two transactivation domains. The N-terminal zinc finger is known to stabilize DNA binding and interact with other zinc finger proteins, whereas the C-terminal zinc finger binds DNA. As such, GATA3 is a member of the GATA family of zinc-finger binding transcription factors that regulates the specification and differentiation of many tissue types including the breast.
In the context of FBC, GATA3 is intimately associated with luminal cell identity and function, and mutated in 11% of patients (Pereira et al., 2016). A truncating splice variant at position 308 is by far the most prevalent hotspot (23% of GATA3 mutations). In MBC, GATA3 is mutated in 15% of patients, and restricted to the luminal B-like breast cancer subtype. These mutations are associated with worse disease-free survival and interestingly, the pattern of mutations found in males does not resemble that of female breast cancers. In fact, the majority of GATA3 mutations found in MBC are frameshift mutations and do not affect the aforementioned hotspot (Piscuoglio et al., 2016).

Gene Name TP53
Location 17p13.1
Protein The structure and function of the TP53 transcription factor have extensively been described elsewhere (http://atlasgeneticsoncology.org/Genes/GC_TP53.html) and will therefore not be repeated here. Mutations in the TP53 gene can be found in 50% of human cancers. More than 80% of TP53 mutations are missense mutations that lead to the synthesis of a stable oncogenic protein that accumulates in the nucleus of tumor cells. In The Cancer Genome Atlas (TCGA) project, six MBC were included, of which none had TP53 mutations (Cancer Genome Atlas Network, 2012). A massively parallel sequencing study based on 59 MBC detected a lower frequency of TP53 mutations in ER-positive/HER2-negative MBC compared with ER-positive/HER2-negative FBC (7% vs. 22%)(Piscuoglio et al., 2016).

Gene Name CCND1
Location 11q13
Protein he CCND1 gene contains 5 coding exons. The structure and function of CCND1 (Cyclin D1) have extensively been described elsewhere (http://atlasgeneticsoncology.org/Genes/BCL1ID36.html) and will therefore not be repeated here. The CCND1 gene is amplified in 12-18% of MBC (Bärlund et al., 2004; Kornegoor et al., 2012; Rizzolo et al., 2016) and amplification is associated with poor prognosis (Kornegoor et al., 2012). Cyclin D1 was shown to be a selective repressor of androgen-dependent signaling and androgen receptor function (Comstock et al., 2011) and a driver of androgen-dependent DNA damage repair, thereby contributing to radioresistance (Casimiro et al., 2016).

Bibliography

Male breast cancer: Looking for better prognostic subgroups
Abreu MH, Afonso N, Abreu PH, Menezes F, Lopes P, Henrique R, Pereira D, Lopes C
Breast 2016 Apr;26:18-24
PMID 27017238
 
In situ male breast carcinoma in the Surveillance, Epidemiology, and End Results database of the National Cancer Institute
Anderson WF, Devesa SS
Cancer 2005 Oct 15;104(8):1733-41
PMID 16138363
 
Secretory carcinoma of the breast containing the ETV6-NTRK3 fusion gene in a male: case report and review of the literature
Arce C, Cortes-Padilla D, Huntsman DG, Miller MA, Dueñnas-Gonzalez A, Alvarado A, Pérez V, Gallardo-Rincón D, Lara-Medina F
World J Surg Oncol 2005 Jun 17;3:35
PMID 15963235
 
Frequent amplification and overexpression of CCND1 in male breast cancer
Bärlund M, Kuukasjärvi T, Syrjäkoski K, Auvinen A, Kallioniemi A
Int J Cancer 2004 Oct 10;111(6):968-71
PMID 15300811
 
Carcinoma of the male breast in Zambia
Bhagwandeen SB
East Afr Med J 1972 Feb;49(2):89-93
PMID 5047279
 
Status of HER-2 in male and female breast carcinoma
Bloom KJ, Govil H, Gattuso P, Reddy V, Francescatti D
Am J Surg 2001 Oct;182(4):389-92
PMID 11720677
 
Cancer Genome Atlas Network
Comprehensive molecular portraits of human breast tumours Nature
PMID 23000897
 
IARC Sci Publ
Cancer incidence in five continents
1976;(15):1-583 PubMed PMID: 66183
PMID 66183
 
Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17
Carey AH, Waterworth D, Patel K, White D, Little J, Novelli P, Franks S, Williamson R
Hum Mol Genet 1994 Oct;3(10):1873-6
PMID 7849715
 
Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer
Casadei S, Norquist BM, Walsh T, Stray S, Mandell JB, Lee MK, Stamatoyannopoulos JA, King MC
Cancer Res 2011 Mar 15;71(6):2222-9
PMID 21285249
 
Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells
Casimiro MC, Di Sante G, Ju X, Li Z, Chen K, Crosariol M, Yaman I, Gormley M, Meng H, Lisanti MP, Pestell RG
Cancer Res 2016 Jan 15;76(2):329-38
PMID 26582866
 
Post-mastectomy radiation in male breast cancer
Chakravarthy A, Kim CR
Radiother Oncol 2002 Nov;65(2):99-103
PMID 12443805
 
PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based subgroups
Cizkova M, Susini A, Vacher S, Cizeron-Clairac G, Andrieu C, Driouch K, Fourme E, Lidereau R, Bièche I
Breast Cancer Res 2012 Feb 13;14(1):R28
PMID 22330809
 
Cyclin D1 is a selective modifier of androgen-dependent signaling and androgen receptor function
Comstock CE, Augello MA, Schiewer MJ, Karch J, Burd CJ, Ertel A, Knudsen ES, Jessen WJ, Aronow BJ, Knudsen KE
J Biol Chem 2011 Mar 11;286(10):8117-27
PMID 21212260
 
The cancer genetics and pathology of male breast cancer
Deb S, Lakhani SR, Ottini L, Fox SB
Histopathology 2016 Jan;68(1):110-8
PMID 26768033
 
Androgen receptor and antiandrogen therapy in male breast cancer
Di Lauro L, Barba M, Pizzuti L, Vici P, Sergi D, Di Benedetto A, Mottolese M, Speirs V, Santini D, De Maria R, Maugeri-Saccà M
Cancer Lett 2015 Nov 1;368(1):20-5
PMID 26276719
 
Risk factors for male breast cancer--a case-control study from Scandinavia
Ewertz M, Holmberg L, Tretli S, Pedersen BV, Kristensen A
Acta Oncol 2001;40(4):467-71
PMID 11504305
 
Cytochrome P450c17alpha gene (CYP17) polymorphism is associated with serum estrogen and progesterone concentrations
Feigelson HS, Shames LS, Pike MC, Coetzee GA, Stanczyk FZ, Henderson BE
Cancer Res 1998 Feb 15;58(4):585-7
PMID 9485002
 
Male breast cancer: a review
Fentiman I
Ecancermedicalscience 2009;3:140
PMID 22276005
 
Male breast cancer
Fentiman IS, Fourquet A, Hortobagyi GN
Lancet 2006 Feb 18;367(9510):595-604
PMID 16488803
 
The Epidemiology of Male Breast Cancer
Ferzoco RM, Ruddy KJ
Curr Oncol Rep 2016 Jan;18(1):1
PMID 26694922
 
Breast cancer in a trans-sexual man receiving hormone replacement therapy
Ganly I, Taylor EW
Br J Surg 1995 Mar;82(3):341
PMID 7796003
 
Analysis of FANCB and FANCN/PALB2 fanconi anemia genes in BRCA1/2-negative Spanish breast cancer families
García MJ, Fernández V, Osorio A, Barroso A, Llort G, Lázaro C, Blanco I, Caldés T, de la Hoya M, Ramón Y Cajal T, Alonso C, Tejada MI, San Román C, Robles-Díaz L, Urioste M, Benítez J
Breast Cancer Res Treat 2009 Feb;113(3):545-51
PMID 18302019
 
A review of the diagnosis and management of male breast cancer
Giordano SH
Oncologist 2005 Aug;10(7):471-9
PMID 16079314
 
Breast carcinoma in men: a population-based study
Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN
Cancer 2004 Jul 1;101(1):51-7
PMID 15221988
 
Breast cancer development in transsexual subjects receiving cross-sex hormone treatment
Gooren LJ, van Trotsenburg MA, Giltay EJ, van Diest PJ
J Sex Med 2013 Dec;10(12):3129-34
PMID 24010586
 
CYP17 promoter polymorphism and breast cancer risk in males and females in relation to BRCA2 status
Gudmundsdottir K, Thorlacius S, Jonasson JG, Sigfusson BF, Tryggvadottir L, Eyfjord JE
Br J Cancer 2003 Mar 24;88(6):933-6
PMID 12644832
 
Loss of heterozygosity at chromosome 11 in breast cancer: association of prognostic factors with genetic alterations
Gudmundsson J, Barkardottir RB, Eiriksdottir G, Baldursson T, Arason A, Egilsson V, Ingvarsson S
Br J Cancer 1995 Sep;72(3):696-701
PMID 7669583
 
Prognostic value of automatically extracted nuclear morphometric features in whole slide images of male breast cancer.
Howlader N, Noone AM, Krapcho M, et al., editors
SEER Cancer Statistics Review Fast Stats: Relative survival by survival time, 1988-2012. Bethesda, MD: National Cancer Institute. http://seer.cancer.gov/faststats/. Last update: September 12, 2016. Date accessed: October 28, 2016.
 
Prevalence of Klinefelter's syndrome in male breast cancer patients
Hultborn R, Hanson C, Köpf I, Verbiené I, Warnhammar E, Weimarck A
Anticancer Res 1997 Nov-Dec;17(6D):4293-7
PMID 9494523
 
Genome methylation patterns in male breast cancer - Identification of an epitype with hypermethylation of polycomb target genes
Johansson I, Lauss M, Holm K, Staaf J, Nilsson C, Fjällskog ML, Ringnér M, Hedenfalk I
Mol Oncol 2015 Oct;9(8):1565-79
PMID 25990542
 
Male breast adenocarcinoma in a prostate cancer patient following prolonged anti-androgen monotherapy
Karamanakos P, Mitsiades CS, Lembessis P, Kontos M, Trafalis D, Koutsilieris M
Anticancer Res 2004 Mar-Apr;24(2C):1077-81
PMID 15154626
 
Kast K, Rhiem K, Wappenschmidt B, Hahnen E, Hauke J, Bluemcke B, Zarghooni V, Herold N, Ditsch N, Kiechle M, Braun M, Fischer C, Dikow N, Schott S, Rahner N, Niederacher D, Fehm T, Gehrig A, Mueller-Reible C, Arnold N, Maass N, Borck G, de Gregorio N, Scholz C, Auber B, Varon-Manteeva R, Speiser D, Horvath J, Lichey N, Wimberger P, Stark S, Faust U, Weber BH, Emons G, Zachariae S, Meindl A, Schmutzler RK, Engel C; German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)
Prevalence of BRCA1/2 germline mutations in 21401 families with breast and ovarian cancer J Med Genet
PMID 26928436
 
Promoter hypermethylation in male breast cancer: analysis by multiplex ligation-dependent probe amplification
Kornegoor R, Moelans CB, Verschuur-Maes AH, Hogenes MCh, de Bruin PC, Oudejans JJ, van Diest PJ
Breast Cancer Res 2012 Jul 5;14(4):R101
PMID 22765268
 
Male breast cancer--an andrological disease: risk factors and diagnosis
Krause W
Andrologia 2004 Dec;36(6):346-54
PMID 15541050
 
Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification
Lacle MM, Kornegoor R, Moelans CB, Maes-Verschuur AH, van der Pol C, Witkamp AJ, van der Wall E, Rueschoff J, Buerger H, van Diest PJ
Mod Pathol 2013 Nov;26(11):1461-7
PMID 23743929
 
Chromosome 17 copy number changes in male breast cancer
Lacle MM, Moelans CB, Kornegoor R, van der Pol C, Witkamp AJ, van der Wall E, Rueschoff J, Buerger H, van Diest PJ
Cell Oncol (Dordr) 2015 Jun;38(3):237-45
PMID 25906114
 
Prognostic value of mitotic index and Bcl2 expression in male breast cancer
Lacle MM, van der Pol C, Witkamp A, van der Wall E, van Diest PJ
PLoS One 2013;8(4):e60138
PMID 23573235
 
Androgen receptor gene mutation in male breast cancer
Lobaccaro JM, Lumbroso S, Belon C, Galtier-Dereure F, Bringer J, Lesimple T, Namer M, Cutuli BF, Pujol H, Sultan C
Hum Mol Genet 1993 Nov;2(11):1799-802
PMID 8281139
 
An international comparison of male and female breast cancer incidence rates
Ly D, Forman D, Ferlay J, Brinton LA, Cook MB
Int J Cancer 2013 Apr 15;132(8):1918-26
PMID 22987302
 
Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, Hollestelle A, Houben M, Crepin E, van Veghel-Plandsoen M, Elstrodt F, van Duijn C, Bartels C, Meijers C, Schutte M, McGuffog L, Thompson D, Easton D, Sodha N, Seal S, Barfoot R, Mangion J, Chang-Claude J, Eccles D, Eeles R, Evans DG, Houlston R, Murday V, Narod S, Peretz T, Peto J, Phelan C, Zhang HX, Szabo C, Devilee P, Goldgar D, Futreal PA, Nathanson KL, Weber B, Rahman N, Stratton MR; CHEK2-Breast Cancer Consortium
Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations Nat Genet
PMID 11967536
 
A cytogenetic study of male breast cancer
Mitchell EL
Cancer Genet Cytogenet 1990 Jul 1;47(1):107-12
PMID 2162731
 
HER2 therapy: molecular mechanisms of trastuzumab resistance
Nahta R, Esteva FJ
Breast Cancer Res 2006;8(6):215
PMID 17096862
 
Role of CHEK2*1100delC in unselected series of non-BRCA1/2 male breast cancers
Neuhausen S, Dunning A, Steele L, Yakumo K, Hoffman M, Szabo C, Tee L, Baines C, Pharoah P, Goldgar D, Easton D
Int J Cancer 2004 Jan 20;108(3):477-8
PMID 14648718
 
Carcinoma of the male breast in Mulago Hospital, Kampala
Ojara EA
East Afr Med J 1978 Oct;55(10):489-91
PMID 738189
 
Male breast cancer
Ottini L, Palli D, Rizzo S, Federico M, Bazan V, Russo A
Crit Rev Oncol Hematol 2010 Feb;73(2):141-55
PMID 19427229
 
The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes
Pereira B, Chin SF, Rueda OM, Vollan HK, Provenzano E, Bardwell HA, Pugh M, Jones L, Russell R, Sammut SJ, Tsui DW, Liu B, Dawson SJ, Abraham J, Northen H, Peden JF, Mukherjee A, Turashvili G, Green AR, McKinney S, Oloumi A, Shah S, Rosenfeld N, Murphy L, Bentley DR, Ellis IO, Purushotham A, Pinder SE, Børresen-Dale AL, Earl HM, Pharoah PD, Ross MT, Aparicio S, Caldas C
Nat Commun 2016 May 10;7:11479
PMID 27161491
 
Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck
Persson M, Andrén Y, Mark J, Horlings HM, Persson F, Stenman G
Proc Natl Acad Sci U S A 2009 Nov 3;106(44):18740-4
PMID 19841262
 
The Genomic Landscape of Male Breast Cancers
Piscuoglio S, Ng CK, Murray MP, Guerini-Rocco E, Martelotto LG, Geyer FC, Bidard FC, Berman S, Fusco N, Sakr RA, Eberle CA, De Mattos-Arruda L, Macedo GS, Akram M, Baslan T, Hicks JB, King TA, Brogi E, Norton L, Weigelt B, Hudis CA, Reis-Filho JS
Clin Cancer Res 2016 Aug 15;22(16):4045-56
PMID 26960396
 
, Easton DF, Stratton MR
Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D; Breast Cancer Susceptibility Collaboration (UK)
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene Nat Genet
PMID 17200668
 
Somatic alterations of targetable oncogenes are frequently observed in BRCA1/2 mutation negative male breast cancers
Rizzolo P, Navazio AS, Silvestri V, Valentini V, Zelli V, Zanna I, Masala G, Bianchi S, Scarnò M, Tommasi S, Palli D, Ottini L
Oncotarget 2016 Nov 8;7(45):74097-74106
PMID 27765917
 
Male breast cancer: genetics, epigenetics, and ethical aspects
Rizzolo P, Silvestri V, Tommasi S, Pinto R, Danza K, Falchetti M, Gulino M, Frati P, Ottini L
Ann Oncol 2013 Nov;24 Suppl 8:viii75-viii82
PMID 24131976
 
Karyotypic findings in two cases of male breast cancer
Rudas M, Schmidinger M, Wenzel C, Okamoto I, Budinsky A, Fazeny B, Marosi C
Cancer Genet Cytogenet 2000 Sep;121(2):190-3
PMID 11063806
 
Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship
Ruddy KJ, Winer EP
Ann Oncol 2013 Jun;24(6):1434-43
PMID 23425944
 
Her-2/neu gene amplification and protein expression in primary male breast cancer
Rudlowski C, Friedrichs N, Faridi A, Füzesi L, Moll R, Bastert G, Rath W, Büttner R
Breast Cancer Res Treat 2004 Apr;84(3):215-23
PMID 15026619
 
Therapeutic strategies in male breast cancer: clinical implications of chromosome 17 gene alterations and molecular subtypes
Schildhaus HU, Schroeder L, Merkelbach-Bruse S, Binot E, Büttner R, Kuhn W, Rudlowski C
Breast 2013 Dec;22(6):1066-71
PMID 24080492
 
, Teixeira MR, Pinto P, Montagna M, Matricardi L, Arason A, Johannsson OT, Barkardottir RB, Jakubowska A, Lubinski J, Izquierdo A, Pujana MA, Balmaña J, Diez O, Ivady G, Papp J, Olah E, Kwong A; Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)
Silvestri V, Barrowdale D, Mulligan AM, Neuhausen SL, Fox S, Karlan BY, Mitchell G, James P, Thull DL, Zorn KK, Carter NJ, Nathanson KL, Domchek SM, Rebbeck TR, Ramus SJ, Nussbaum RL, Olopade OI, Rantala J, Yoon SY, Caligo MA, Spugnesi L, Bojesen A, Pedersen IS, Thomassen M, Jensen UB, Toland AE, Senter L, Andrulis IL, Glendon G, Hulick PJ, Imyanitov EN, Greene MH, Mai PL, Singer CF, Rappaport-Fuerhauser C, Kramer G, Vijai J, Offit K, Robson M, Lincoln A, Jacobs L, Machackova E, Foretova L, Navratilova M, Vasickova P, Couch FJ, Hallberg E, Ruddy KJ, Sharma P, Kim SW; kConFab Investigators
, Nevanlinna H, Aittomäki K, Perez Segura P, Caldes T, Van Maerken T, Poppe B, Claes KB, Isaacs C, Elan C, Lasset C, Stoppa-Lyonnet D, Barjhoux L, Belotti M, Meindl A, Gehrig A, Sutter C, Engel C, Niederacher D, Steinemann D, Hahnen E, Kast K, Arnold N, Varon-Mateeva R, Wand D, Godwin AK, Evans DG, Frost D, Perkins J, Adlard J, Izatt L, Platte R, Eeles R, Ellis S; EMBRACE , Hamann U, Garber J, Fostira F, Fountzilas G, Pasini B, Giannini G, Rizzolo P, Russo A, Cortesi L, Papi L, Varesco L, Palli D, Zanna I, Savarese A, Radice P, Manoukian S, Peissel B, Barile M, Bonanni B, Viel A, Pensotti V, Tommasi S, Peterlongo P, Weitzel JN, Osorio A, Benitez J, McGuffog L, Healey S, Gerdes AM, Ejlertsen B, Hansen TV, Steele L, Ding YC, Tung N, Janavicius R, Goldgar DE, Buys SS, Daly MB, Bane A, Terry MB, John EM, Southey M, Easton DF, Chenevix-Trench G, Antoniou AC, Ottini L
PMID 26857456
 
Analysis of familial male breast cancer for germline mutations in CHEK2
Sodha N, Wilson C, Bullock SL, Phillimore H, Houlston RS, Eeles RA
Cancer Lett 2004 Nov 25;215(2):187-9
PMID 15488637
 
Long CAG repeat sequence and protein expression of androgen receptor considered as prognostic indicators in male breast carcinoma
Song YN, Geng JS, Liu T, Zhong ZB, Liu Y, Xia BS, Ji HF, Li XM, Zhang GQ, Ren YL, Li ZG, Pang D
PLoS One 2012;7(12):e52271
PMID 23272232
 
The rising incidence of male breast cancer
Speirs V, Shaaban AM
Breast Cancer Res Treat 2009 May;115(2):429-30
PMID 18478326
 
Decline in breast cancer incidence in the United States: what about male breast cancer? Breast Cancer Res Treat
Stang A, Thomssen C
2008 Dec;112(3):595-6 doi: 10
PMID 18176840
 
CHEK2 1100delC is not a risk factor for male breast cancer population
Syrjäkoski K, Kuukasjärvi T, Auvinen A, Kallioniemi OP
Int J Cancer 2004 Jan 20;108(3):475-6
PMID 14648717
 
Breast adenoid cystic carcinoma in a 19-year-old man: a case report and review of the literature
Tang P, Yang S, Zhong X, Yao J, Zhang Y, Dong H, Li G
World J Surg Oncol 2015 Feb 6;13:19
PMID 25885366
 
Thompson D, Easton D; Breast Cancer Linkage Consortium
Variation in cancer risks, by mutation position, in BRCA2 mutation carriers Am J Hum Genet
PMID 11170890
 
A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes
Thorlacius S, Olafsdottir G, Tryggvadottir L, Neuhausen S, Jonasson JG, Tavtigian SV, Tulinius H, Ogmundsdottir HM, Eyfjörd JE
Nat Genet 1996 May;13(1):117-9
PMID 8673089
 
Gene copy number variation in male breast cancer by aCGH
Tommasi S, Mangia A, Iannelli G, Chiarappa P, Rossi E, Ottini L, Mottolese M, Zoli W, Zuffardi O, Paradiso A
Anal Cell Pathol (Amst) 2010;33(3):113-9
PMID 21045282
 
Do columnar cell lesions exist in the male breast? Histopathology
Verschuur-Maes AH, Kornegoor R, de Bruin PC, Oudejans JJ, van Diest PJ
2014 May;64(6):818-25 doi: 10
PMID 24267518
 
Prognostic value of automatically extracted nuclear morphometric features in whole slide images of male breast cancer
Veta M, Kornegoor R, Huisman A, Verschuur-Maes AH, Viergever MA, Pluim JP, van Diest PJ
Mod Pathol 2012 Dec;25(12):1559-65
PMID 22899294
 
CHEK2 1100delC and male breast cancer in the Netherlands
Wasielewski M, den Bakker MA, van den Ouweland A, Meijer-van Gelder ME, Portengen H, Klijn JG, Meijers-Heijboer H, Foekens JA, Schutte M
Breast Cancer Res Treat 2009 Jul;116(2):397-400
PMID 18759107
 
Frequent allelic losses on chromosome 13q in human male breast carcinomas
Wingren S, van den Heuvel A, Gentile M, Olsen K, Hatschek T, Söderkvist P
Eur J Cancer 1997 Dec;33(14):2393-6
PMID 9616288
 
A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome
Wooster R, Mangion J, Eeles R, Smith S, Dowsett M, Averill D, Barrett-Lee P, Easton DF, Ponder BA, Stratton MR
Nat Genet 1992 Oct;2(2):132-4
PMID 1303262
 
A polymorphism in the CYP17 gene is associated with male breast cancer
Young IE, Kurian KM, Annink C, Kunkler IH, Anderson VA, Cohen BB, Hooper ML, Wyllie AH, Steel CM
Br J Cancer 1999 Sep;81(1):141-3
PMID 10487625
 
Aromatase inhibitors in male breast cancer: a pooled analysis
Zagouri F, Sergentanis TN, Azim HA Jr, Chrysikos D, Dimopoulos MA, Psaltopoulou T
Breast Cancer Res Treat 2015 May;151(1):141-7
PMID 25850534
 
Prognostic models in male breast cancer
van der Pol CC, Lacle MM, Witkamp AJ, Kornegoor R, Miao H, Bouchardy C, Borel Rinkes I, van der Wall E, Verkooijen HM, van Diest PJ
Breast Cancer Res Treat 2016 Nov;160(2):339-346
PMID 27671991
 

Citation

This paper should be referenced as such :
Moelans CB, van der Groep P, J van Diest P
Male breast cance
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Tumors/MaleBreastID6242.html


Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

Genes BRCA2 MIR100

External links

arrayMap arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaseMale breast cancer
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed


© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Jun 17 12:10:35 CEST 2017


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.