Status of HER-2 in male and female breast carcinoma

Bloom, Kenneth J.; Govil, Hema; Gattuso, Paolo; Reddy, Vijaya B.; Francescatti, Darius

doi:10.1016/s0002-9610(01)00733-4

Cited by 117 publications

(79 citation statements)

References 23 publications

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“…These highly variable results might be due to different antigen retrieval techniques, fixatives and antibodies, as well as to differences in the scoring systems. 1 Recently, Bloom et al 15 applied strict criteria to define positive ERBB2 staining and found overexpression in only 1.7% of specimens, which is consistent with our results. The low ERBB2 amplification and overexpression frequencies indicate that MBC is clearly distinct from FBC, where ERBB2 alterations are seen in 10 -34% of tumors.…”

Section: Discussionsupporting

confidence: 91%

“…ERBB2 amplification was detected in a single case confirming the results from a previous study where no amplification was detected among 58 samples. 15 Although only a single tumor with ERBB2 amplification was found, we decided to evaluate the ERBB2 protein expression levels because of the clinical significance of this gene in FBC. 6,7 The number of male breast tumors with ERBB2 overexpression was also low (4%).…”

Section: Discussionmentioning

confidence: 99%

“…1 ERBB2 amplification has been assessed in a single study and no amplifications were observed. 15 The aim of our present study was to evaluate the potential involvement of genes commonly amplified in FBC in a large series of MBC using the TMA technology. Amplification frequencies of ERBB2, MYC, CCND1, ZNF217 and PPM1D were investigated in 128 MBC specimens using FISH and the protein expression levels of ER, PR, CCND1 and ERBB2 were evaluated using IHC.…”

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confidence: 99%

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Frequent amplification and overexpression of CCND1 in male breast cancer

Bärlund

Kuukasjärvi

Syrjäkoski

et al. 2004

Intl Journal of Cancer

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Genetic events underlying the pathogenesis of breast cancer have been studied extensively and several clinically significant markers have been identified. For example, amplification and overexpression of the ERBB2 oncogene is associated with poor prognosis in breast cancer and ERBB2 serves as a target for antibody-based therapy. Current knowledge on the pathogenesis of male breast cancer (MBC) is limited. The purpose of our study was to investigate the potential relevance of a series of genes known to be amplified in female breast cancer (FBC) in a the development and pathogenesis of MBC. To this end, we applied fluorescence in situ hybridization and immunohistochemistry to the analysis of 128 breast tumors from males. Amplification of ERBB2, MYC, PPM1D and ZNF217 was detected rarely (1-2% of tumors) indicating a considerably lower amplification frequency than in FBC. CCND1 amplification was observed in 12% of cases, being in good concordance with findings from FBC. In addition, CCND1 overexpression was detected in 63% of tumors and was associated with ER positivity (p < 0.0001). Our results indicate distinct differences in the genetic basis of MBC and FBC and suggest that marked differences exist in the pathogenesis of these diseases. The lack of ERBB2 involvement was especially unexpected and implies that ERBB2-targeted therapies are unlikely to be beneficial in MBC. Furthermore, the high frequency of hormone receptor positivity and the association between ER positivity and CCND1 overexpression supports the notion that hormonal regulation is likely to be essential for the development of MBC. © 2004 Wiley-Liss, Inc. Key words: male breast cancer; gene amplification; CCND1; tissue microarrayMale breast cancer (MBC) is a rare disease, representing Ͻ1% of all breast cancers and Ͻ1% of all cancers in men. 1,2 All histological types of breast cancer have been identified in men, with infiltrating ductal carcinoma representing about 80% of cases. Similarly to FBC, hormonal, genetic, and environmental factors are involved in the etiology of MBC. 3 Conditions associated with increased estrogen or decreased androgen levels, such as Klinefelter syndrome and testicular disorders, predispose to MBC. 1 Particularly, the Klinefelter syndrome, characterized by 47,XXY karyotype, is associated with a 50-fold increase in breast cancer risk. 4 The genetic factor most clearly associated with MBC is BRCA2 germline mutation and its frequency in men with breast cancer varies considerably (4 -40%) depending on the population investigated. 3,5 Germline BRCA1 mutations are also found in male breast cancer patients. 5 The possible role and clinical utility of oncogene alterations have been widely investigated in FBC. The most extensively studied is the ERBB2 oncogene that belongs to the epidermal growth factor receptor family. ERBB2 is amplified and overexpressed in 10 -34% of FBC and has been shown to have prognostic and predictive value. 6 Targeted therapy against ERBB2 is currently undergoing clinical trials and shows potential benefit...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Frequent amplification and overexpression of CCND1 in male breast cancer

Bärlund

Kuukasjärvi

Syrjäkoski

et al. 2004

Intl Journal of Cancer

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“…The need for more refined therapeutic treatments for male breast cancer (MBC) is evidenced by a steady stream of publications highlighting gender-specific differences using IHC (1-5), genetics (6)(7)(8)(9)(10)(11), and more recently, epigenetics (12)(13)(14)(15). Of note, although MBC is similar histologically to female breast cancer (FBC), with the same panel of biomarkers used to guide treatment and prognosis, more rigorous interrogation of the underlying genetics shows heterogeneity in MBC as recognized in FBC where molecular profiling has identified different subgroups that correlate with varying clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Humphries

Rajan

Droop

et al. 2017

Clinical Cancer Research

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Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n ¼ 477, training; n ¼ 220, validation set) and quantified in pre-and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P ¼ 0.013; HR ¼ 1.77, 1.12-2.8 and P ¼ 0.035; HR ¼ 1.68, 1.03-2.74, respectively), or when coexpressed (P ¼ 0.01; HR ¼ 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P ¼ 0.016; HR ¼ 2.38 (1.18-4.8), eIF5 P ¼ 0.022; HR ¼ 2.55 (1.14-5.7); coexpression P ¼ 0.001; HR ¼ 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.

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“…As with the incidence in women, the incidence of breast cancer in men has increased (to 1.08 in 100,000 in 1998 from 0.86 in 100,000 in 1973) 2 . Overexpression of the human epidermal growth factor receptor 2 (her2), a negative prognostic factor in women, is found less often in men 7 . Men are more frequently er and pr positive, perhaps indicating increased proliferative activity 8 .…”

Section: Discussionmentioning

confidence: 99%

Ductal Carcinoma In Situ in a 25-Year-Old Man Presenting with Apparent Unilateral Gynecomastia

Coroneos

Hamm

2010

Current Oncology

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Ductal carcinoma in situ (dcis) in a young man is rarely reported. Our patient, a 25-year-old man, presented with apparent symptomatic unilateral gynecomastia. He has a strong history of cancer on both the maternal and paternal sides of his family, including breast and lung (maternal) and melanoma, colon, and pancreatic (paternal). His mother tested negative for BRCA1 and BRCA2. There is no information on paternal genetic testing.The patient was treated with left subcutaneous mastectomy. Upon histologic review of the sample, concurrent gynecomastia and dcis were discovered. To date, only 4 cases of gynecomastia and dcis have been described in younger male patients. Because only 30%-50% of patients with dcis eventually develop invasive cancer in the subsequent 10-20 years, dcis prevalence in the general population may be higher than predicted. This case underscores the importance of family history in any patient presenting with a breast mass. Patients must be made aware of the risk, however small it may be, and physicians must remain cautious of cancer in young men with gynecomastia. KEY WORDSGynecomastia, ductal carcinoma in situ, male breast cancer

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Status of HER-2 in male and female breast carcinoma

Cited by 117 publications

References 23 publications

Frequent amplification and overexpression of CCND1 in male breast cancer

Frequent amplification and overexpression of CCND1 in male breast cancer

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Ductal Carcinoma In Situ in a 25-Year-Old Man Presenting with Apparent Unilateral Gynecomastia

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