Cases Of Male Breast Cancer Research Articles

Germline investigation in male breast cancer of DNA repair genes by next-generation sequencing.

In order to better define the breast cancer (BC) genetic risk factors in men, a germline investigation was carried out on 81 Male BC cases by screening the 24 genes involved in BC predisposition, genome stability maintenance and DNA repair mechanisms by next-generation sequencing. Germline DNAs were tested in a custom multi-gene panel focused on all coding exons and exon-intron boundaries of 24 selected genes using two amplicon-based assays on PGM-Ion Torrent (ThermoFisher Scientific) and MiSeq (Illumina) platforms. All variants were recorded and classified by using a custom pipeline. Clinical pathological data and the family history of 81 Male BC cases were gathered and analysed, revealing the average age of onset to be 61.3years old and that in 35 cases there was a family history of BC. Our genetic screening allowed us to identify a germline mutation in 22 patients (23%) in 4 genes: BRCA2, BRIP1, MUTYH and PMS2. Moreover, 12 variants of unknown clinical significance (VUS) in 9 genes (BARD1, BRCA1, BRIP1, CHEK2, ERCC1, NBN, PALB2, PMS1, RAD50) were predicted as potentially pathogenic by in silico analysis bringing the mutation detection rate up to 40%. As expected, a positive family history is a strong predictor of germline BRCA2 mutations in male BC. Understanding the potential pathogenicity of VUS represents an extremely urgent need for the management of BC risk in Male BC cases and their own families.

Evaluation of CYP17A1 and CYP1B1 polymorphisms in male breast cancer risk.

Breast cancer in men is a rare and still poorly characterized disease. Inherited mutations in BRCA1, BRCA2 and PALB2 genes, as well as common polymorphisms, play a role in male breast cancer genetic predisposition. Male breast cancer is considered a hormone-dependent tumor specifically related to hyperestrogenism. Polymorphisms in genes involved in estrogen biosynthesis and metabolism pathways, such as CYP17A1 and CYP1B1, have been associated with breast cancer risk. Here, we aimed to investigate the role of CYP17A1 and CYP1B1 polymorphisms in male breast cancer risk. A series of 597 male breast cancer cases and 1022 male controls, recruited within the Italian Multicenter Study on male breast cancer, was genotyped for CYP17A1 rs743572, CYP1B1 rs1056836 and rs1800440 polymorphisms by allelic discrimination real-time PCR with TaqMan probes. Associations with male breast cancer risk were estimated using logistic regression. No statistically significant associations between male breast cancer risk and the three analyzed polymorphisms emerged. Similar results were obtained also when BRCA1/2 mutational status was considered. No significant differences in the distribution of the genotypes according to estrogen receptor status emerged. In conclusion, our study, based on a large series of male breast cancer cases, is likely to exclude a relevant role of CYP17A1 and CYP1B1 polymorphisms in male breast cancer predisposition. Overall, these results add new data to the increasing evidence that polymorphisms in these genes may not be associated with breast cancer risk.

Comorbidity and racial differences in risk of mortality of men with breast cancer.

1554 Background: Black men with breast cancer have more concomitant disease and worse survival than white men. Less is known about concomitant disease and survival in Hispanic and Asian/Pacific Islander (API) men with breast cancer. The purpose of this study was to compare differences in survival and risk of mortality of white, black, Hispanic, and Asian/Pacific Islander (API) men with breast cancer with increasing comorbidity. Methods: We identified 1,497 cases of first primary male invasive breast cancer from the California Cancer Registry 2000-2015 with a documented Charlson Comorbidity Index (CCI). The CCI is a weighted index based on the presence of certain comorbid conditions following a cancer diagnosis and weighted by the severity of these conditions. A score of 0 indicates no significant comorbidity and scores of 2 or more are interpreted as a high comorbidity burden. Bivariate associations between race and AJCC stage, tumor grade, estrogen receptor (ER) status, human epidermal growth factor 2 (HER2), and socioeconomic status (SES) were compared using the χ2 Test of Independence. Kaplan Meier Survival analysis was used to compare unadjusted survival among the races. Cox Regression was used to assess risk of mortality for each race when adjusted for factors that had a statistically significant (p < 0.10) bivariate association with race/ethnicity. Analyses were conducted within each level of the CCI (0, 1, and 2 or more). Results: Among men with a CCI of 0 or 2, blacks had worse unadjusted survival than whites. There were no differences in survival for men with a CCI of 1. Stage, SES, ER, and type of surgery all had statistically significant bivariate associations with race/ethnicity. For men with a CCI of 0, Hispanics (HR = 0.367; 95% CI = 0.167, 0.801) and APIs (HR = 0.422; 95% CI = 0.189, 0.941) had a reduced risk of mortality when compared with whites. Black men had the same risk of mortality as white men. There were no differences in risk of mortality by race for men with a CCI of 1 or 2. Conclusions: Black men with breast cancer and no comorbidity have the same risk of mortality as white men while Hispanic and API men have lower risk of mortality. There are no racial disparities in adjusted risk of mortality in men with breast cancer with any concomitant disease.

Finasteride Use and Risk of Male Breast Cancer: A Case-Control Study Using Individual-Level Registry Data from Denmark, Finland, and Sweden.

In case reports, concerns have been raised as to whether finasteride use increases the risk of male breast cancer. Previous epidemiologic evidence on the potential link is conflicting. This study aimed to assess whether an association between finasteride use and male breast cancer exists after accounting for potential confounders. The source population consisted of all men (≥35 years) from Denmark (1995-2014), Finland (1997-2013), and Sweden (2005-2014). Cases with incident male breast cancer were identified in the cancer registries and matched with 50 density-sampled, age, and country-matched male population controls per case. Exposure information on finasteride use was derived from the prescription registries. Potential confounders were identified using the directed acyclic graph methodology and measured by use of information from nation-wide registries. The study population comprised 1,005 male breast cancer cases and 43,058 controls. Confounder-adjusted odds of finasteride exposure were not statistically significantly increased [OR, 1.09; 95% confidence interval (CI), 0.77-1.54] in breast cancer cases relative to controls. There was no evidence of a dose-response relationship, as the group with greatest exposure to finasteride was associated with lowest OR of male breast cancer [OR, 0.72 (95% CI, 0.40-1.30)]. Sensitivity analyses did not reveal marked changes in results with different exposure definitions or for specific subgroups. Results from this study provided no evidence that finasteride use was associated with male breast cancer. This large confounder-adjusted study supports the view that exposure to finasteride is not associated materially with male breast cancer risk.

Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy.

Breast cancer (BC) in men is rare and genetic predisposition is likely to play a relevant role in its etiology. Inherited mutations in BRCA1/2 account for about 13% of all cases and additional genes that may contribute to the missing heritability need to be investigated. In our study, a well-characterized series of 523 male BC (MBC) patients from the Italian multicenter study on MBC, enriched for non-BRCA1/2 MBC cases, was screened by a multigene custom panel of 50 cancer-associated genes. The main clinical-pathologic characteristics of MBC in pathogenic variant carriers and non-carriers were also compared. BRCA1/2 pathogenic variants were detected in twenty patients, thus, a total of 503 non-BRCA1/2 MBC patients were examined in our study. Twenty-seven of the non-BRCA1/2 MBC patients were carriers of germline pathogenic variants in other genes, including two APC p.Ile1307Lys variant carriers and one MUTYH biallelic variant carrier. PALB2 was the most frequently altered gene (1.2%) and PALB2 pathogenic variants were significantly associated with high risk of MBC. Non-BRCA1/2 pathogenic variant carriers were more likely to have personal (p = 0.0005) and family (p = 0.007) history of cancer. Results of our study support a central role of PALB2 in MBC susceptibility and show a low impact of CHEK2 on MBC predisposition in the Italian population. Overall, our data indicate that a multigene testing approach may benefit from appropriately selected patients with implications for clinical management and counseling of MBC patients and their family members.

Contribution of MUTYH Variants to Male Breast Cancer Risk: Results From a Multicenter Study in Italy.

Inherited mutations in BRCA1, and, mainly, BRCA2 genes are associated with increased risk of male breast cancer (MBC). Mutations in PALB2 and CHEK2 genes may also increase MBC risk. Overall, these genes are functionally linked to DNA repair pathways, highlighting the central role of genome maintenance in MBC genetic predisposition. MUTYH is a DNA repair gene whose biallelic germline variants cause MUTYH-associated polyposis (MAP) syndrome. Monoallelic MUTYH variants have been reported in families with both colorectal and breast cancer and there is some evidence on increased breast cancer risk in women with monoallelic variants. In this study, we aimed to investigate whether MUTYH germline variants may contribute to MBC susceptibility. To this aim, we screened the entire coding region of MUTYH in 503 BRCA1/2 mutation negative MBC cases by multigene panel analysis. Moreover, we genotyped selected variants, including p.Tyr179Cys, p.Gly396Asp, p.Arg245His, p.Gly264Trpfs*7, and p.Gln338His, in a total of 560 MBC cases and 1,540 male controls. Biallelic MUTYH pathogenic variants (p.Tyr179Cys/p.Arg241Trp) were identified in one MBC patient with phenotypic manifestation of adenomatous polyposis. Monoallelic pathogenic variants were identified in 14 (2.5%) MBC patients, in particular, p.Tyr179Cys was detected in seven cases, p.Gly396Asp in five cases, p.Arg245His and p.Gly264Trpfs*7 in one case each. The majority of MBC cases with MUTYH pathogenic variants had family history of cancer including breast, colorectal, and gastric cancers. In the case-control study, an association between the variant p.Tyr179Cys and increased MBC risk emerged by multivariate analysis [odds ratio (OR) = 4.54; 95% confidence interval (CI): 1.17–17.58; p = 0.028]. Overall, our study suggests that MUTYH pathogenic variants may have a role in MBC and, in particular, the p.Tyr179Cys variant may be a low/moderate penetrance risk allele for MBC. Moreover, our results suggest that MBC may be part of the tumor spectrum associated with MAP syndrome, with implication in the clinical management of patients and their relatives. Large-scale collaborative studies are needed to validate these findings.

Combination Technique Is Superior to Dye Alone in Identification of the Sentinel Lymph Node in Male Breast Cancer

Sentinel lymph node (SLN) biopsy is the main method in staging the axilla. There are insufficient data available regarding the accuracy of an SLN biopsy in male breast cancer. The aim of this study is to evaluate whether the combination of dye and radiotracer would improve the detection rate of SLNs versus dye alone in male breast cancer patients. From February 2009 to January 2012, our SLN biopsy database was retrospectively reviewed to identify male breast cancer cases. Of the 890 SLN procedures contained in the database, 10 male breast cancer patients were identified. Patient age, body mass index, SLN biopsy technique, SLN identification, number of SLN excised, and pathology reports were reviewed. Mean age was 57.2 (34-85) years with a mean tumor size was 2.2 (1.0-4.0) cm. SLN detection ratios were two in four with blue dye and six in six with the combination technique. Overall, SLNs were identified in 8 of the 10 patients. SLN biopsy is applicable in male breast cancer cases. The addition of a radiotracer to the dye in SLN biopsy increases the detection rate of sentinel nodes in male breast cancer patients.

Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer

Breast cancer can occur in either gender; however, it is rare in men, accounting for <1% of diagnosed cases. In a previous transcriptomic screen of male breast cancer (MBC) and female breast cancer (FBC) occurrences, we observed that Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was to confirm the expression of STC2 in MBC and to investigate whether this had an impact on patient prognosis. Following an earlier transcriptomic screen, STC2 gene expression was confirmed by RT‐qPCR in matched MBC and FBC samples as well as in tumour‐associated fibroblasts derived from each gender. Subsequently, STC2 protein expression was examined immunohistochemically in tissue microarrays containing 477 MBC cases. Cumulative survival probabilities were calculated using the Kaplan–Meier method and multivariate survival analysis was performed using the Cox hazard model. Gender‐specific STC2 gene expression showed a 5.6‐fold upregulation of STC2 transcripts in MBC, also supported by data deposited in Oncomine™. STC2 protein expression was a positive prognostic factor for disease‐free survival (DFS; Log‐rank; total p = 0.035, HR = 0.49; tumour cells p = 0.017, HR = 0.44; stroma p = 0.030, HR = 0.48) but had no significant impact on overall survival (Log‐rank; total p = 0.23, HR = 0.71; tumour cells p = 0.069, HR = 0.59; stroma p = 0.650, HR = 0.87). Importantly, multivariate analysis adjusted for patient age at diagnosis, node staging, tumour size, ER, and PR status revealed that total STC2 expression as well as expression in tumour cells was an independent prognostic factor for DFS (Cox regression; p = 0.018, HR = 0.983; p = 0.015, HR = 0.984, respectively). In conclusion, STC2 expression is abundant in MBC where it is an independent prognostic factor for DFS.

BRCA1 and BRCA2 Mutations Other Than the Founder Alleles Among Ashkenazi Jewish in the Population of Argentina

In Ashkenazi Jewish (AJ) high risk families 3 mutations [2 in BRCA1 (c. 68_69del and c.5266dup) and 1 in BRCA2 (c.5946del)] account for the majority of high risk breast and ovarian cancer cases in that ethnic group. Few studies with limited number of genotyped individuals have expanded the spectrum of mutations in both BRCA genes beyond the 3 mutation panel. In this study, 279 high risk individual AJ were counseled at CEMIC (Centro de Educación Médica e Investigaciones Clínicas), and were genotyped first for the 3 recurrent mutation panel followed by Next Generation Sequencing (NGS) of BRCA1 BRCA2 in 76 individuals who tested negative for the first genotyping step. Of 279 probands (259 women), 55 (50 women) harbored one of the 3 mutations (19.7%); Of 76 fully sequenced cases (73 women), 6 (5 women) (7.9%) carried a pathogenic mutation: in BRCA1, c.2728C>T - p.(Gln910*); c.5407-?_(*1_?)del and c.5445G>A - p.(Trp1815*); in BRCA2, c.5351dup - p.(Asn1784Lysfs*3); c.7308del - p.(Asn2436Lysfs*33) and c.9026_9030del - p.(Tyr3009Serfs*7). Of 61 mutation carriers the distribution was as follows: 11 cancer free at the time of genotyping, 34 female breast cancer cases with age range 28–72 years (41.6 ± 9.3), 3 male breast cancer cases with age range 59–75 years (65 ± 7.3), 6 breast and ovarian cancer cases with age range 35–60 years (breast 40.4 ± 5.2; ovary 47.8 ± 7.2) and 7 ovarian cancer cases with age range 41–77 years (60.6 ± 13.3). This information proved highly useful for counseling, treatment, and prevention for the patient and the family. In conclusion comprehensive BRCA1/2 testing in AJ high risk breast ovarian cancer cases adds valuable clinically relevant information in a subset of cases estimated up to 7% and is therefore recommended.

Abstract 1236: Insight into genetic susceptibility to BRCA-negative male breast cancer by multigene panel testing: Results from a multicenter study in Italy

Abstract Background: Male breast cancer (MBC) is a rare disease, representing less than 1% of all breast cancers (BC). Although rare, MBC remains a substantial cause for morbidity and mortality in men. MBC etiology appears to be largely associated with genetic factors. Inherited mutations in BRCA2, PALB2 and BRCA1 genes, predispose to MBC and account for about 15% of all cases. Thus, a fraction of MBC cases remains to be assigned to specific genetic factors. Here, we aimed at investigating the genetic component of BRCA1/2 mutation negative MBC cases and at identifying germline mutations that could further explain MBC genetic susceptibility. Materials and methods: We performed a genomic screening of a well-characterized series of 502 BRCA1/2 mutation negative Italian MBC cases by a comprehensive multi-gene custom panel of 50 cancer-related genes, using MiniSeq platform (Illumina). We also compared the main clinical-pathologic characteristics of MBCs in mutation carriers and non-carriers using Fisher exact test and t-test, where appropriate. All statistical analyses were performed with the R software (www.r-project.org). Results: Overall 6% of BRCA1/2 mutation negative MBC cases were found to carry a pathogenic variant in the genes analyzed. In particular, PALB2 and ATM were the most frequently altered genes (1.1% and 0.7%, respectively). Mutations in known/proposed BC genes, such as BARD1, BLM, BRIP1, CASP8, CHEK2, FANCM, NBN, NF1, RAD50, RAD51C and RAD51D, as well as in genes considered not closely related to BC predisposition, such as APC, EPCAM and MUTYH, were also identified. Intriguingly, the same NBN mutation was identified in three unrelated MBC cases. Mutation carriers were more likely to have a personal history of cancer in addition to MBC (p=0.0045) and family history of cancer other than breast and ovarian cancer (p=0.0004). Conclusions: This study may help to gain more insight into the genetic susceptibility of MBC. Our results support the central role of PALB2 in MBC susceptibility, point to a relevant role of ATM and confirm a low impact of CHEK2 mutations on MBC predisposition in the Italian population. Considering that pathogenic mutations were found only in a fraction of the genes analyzed, our data indicate that the identification of the more appropriate genes for the genomic screening of MBC cases is essential in order to develop a comprehensive and specific MBC susceptibility panel with implications for clinical management and counselling of patients and their families. Moreover, our results suggest that multigene testing approach may benefit appropriately selected patients, especially those with a personal or family history of cancer other than breast/ovarian cancer. Study supported by AIRC (IG 16933) to L.O. Citation Format: Piera Rizzolo, Veronica Zelli, Valentina Silvestri, Virginia Valentini, Alessandro Spinelli, Maria Grazia Tibiletti, Antonio Russo, Liliana Varesco, Giuseppe Giannini, Daniele Calistri, Laura Cortesi, Alessandra Viel, Marco Montagna, Paolo Peterlongo, Paolo Radice, Domenico Palli, Laura Ottini. Insight into genetic susceptibility to BRCA-negative male breast cancer by multigene panel testing: Results from a multicenter study in Italy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1236.

Abstract 1225: Rare variants in DNA damage repair genes are associated with male breast cancer predisposition

Abstract Male breast cancer accounts for approximately 1% of all breast cancers diagnosed each year in the UK. Germline mutations in DNA damage response genes are known to be associated with many forms of cancer, including breast cancer. In order to identify low frequency male breast cancer predisposition genes, we performed targeted resequencing of more than 300 genes that were selected on the basis of involvement in DNA maintenance and repair pathways. Using a cost-effective protocol based on an automated library preparation method and a multiplexed hybridization enrichment step, we sequenced 1,029 male breast cancer cases from the UK Breast Cancer Now male breast cancer study (MBCS) and 1,254 controls from the MBCS and the ICR1000 UK exome series. Rare variants localising to 19 genes were significantly associated with risk of male breast cancer. Genes with an excess of rare coding mutations included the known breast cancer susceptibility genes BRCA2, CHEK2 and ATM as well as multiple members of the Fanconi anaemia (FA) pathway. Loss of heterozygosity (LOH) affecting the wildtype allele of putative predisposition genes was observed more than 10% of cases with matched tumor samples. In addition to LOH in BRCA2 mutation carries, somatic losses were observed that affected CCNE1, ATM, PALB2, BARD1, CHEK2, POLL and RAD9A. These data represent the largest analysis of rare variants in male breast cancer to date and have enabled the identification of known and putative novel susceptibility genes. Citation Format: Sarah L. Maguire, Katarzyna Tomczyk, Eleni Perrakis, Edward Saunders, Daniel Leongamornlert, ZSofia Kote-Jarai, Rosalind Eeles, Montserrat Garcia-Closas, Paul Pharoah, Douglas Easton, Christopher J. Lord, Alan Ashworth, Anthony Swerdlow, Nick Orr. Rare variants in DNA damage repair genes are associated with male breast cancer predisposition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1225.

Characteristics and treatment prognosis of 23 cases of male breast cancer.

e12595Background: To investigate the characteristics, treatment and prognosis of male breast cancer(MBC). Methods: :A total of 23 cases of male breast cancer in our hospital from August 2006 to Jul...

Mutational analysis of candidate genes in Israeli male breast cancer cases.

To define the mutational spectrum of several candidate gene mutations in Israeli male breast cancer cases. MBC cases counselled at the Oncogenetics unit, Sheba Medical Center from January 1998 to June 2017 were included. Relevant clinical and oncological data and cancer phenotype were retrieved. All participants were genotyped for the predominant Jewish BRCA1 and BRCA2 germline mutations using a chip-based assay. Those who tested negative were further genotyped for three recurring mutations in CHEK2 (c.1100delC, p.S428F, p.I157T), and single mutations in the FANCM (c.5791C>T), and RAD51D (c.556C>T) genes, by direct sequencing. The ethics committee approved the study. Overall, 61 MBC were identified and genotyped, 41 (67.2%) were Ashkenazim, age at diagnosis was 58.1 ± 12.6years, and 31 (50.8%) had a family history of cancer. Of genotyped individuals, one (1.6%) harboured the 185delAG* BRCA1 mutation, 7 (11.4%) the 6174delT*BRCA2 mutation and 2 (3.2%) other recurring mutations in BRCA2 (overall 10/61-16.4% BRCA1/BRCA2 mutation carriers). Of BRCA-negative cases, 3/51 (5.9%) carried the p.S428F *CHEK2 mutation. None was a carrier of the other genotyped mutations in CHEK2, FANCM or RAD51D. BRCA1, BRCA2 and CHEK2 germline mutations contribute to inherited predisposition to MBC in Israel.

Forkhead box M1 (FOXM1) expression predicts disease free survival and may mediate resistance to chemotherapy and hormonotherapy in male breast cancer.

Male breast cancer (MBC) is a rare and neglected disease. Prognostic and predictive factors in MBC are extrapoled from trials conducted on its female counterpart. Since the relationship between the transcription factor Forkhead box M1 (FOXM1) expression and the clinical response to chemotherapy and hormonotherapy in MBC remains unknown, we sought to investigate the predictive value of FOXM1 in MBC. FOXM1 expression was assessed in 130 MBC cases. Clinical significance was analyzed by Kaplan Meier curves, log-rank test and multivariate Cox regression analyses. Patients with high FOXM1 expression had a significantly lower response rate to chemotherapy (P = 0.045) and hormonotherapy (P = 0.029) than those with low FOXM1 expression. Multivariate analyses indicated that FOXM1 was an independent prognostic factor for disease free survival in MBC patients (P < 0.001). FOXM1 may have a reliable predictive significance in male breast cancer and thus may become an important target for male breast cancer therapy in the near future.

Abstract P5-23-03: Gene expression profiling in male breast cancer

Abstract Background: Tumor gene expression profiling tests are widely used to quantify risk of recurrence of breast cancer and guide systemic therapy in early stage breast cancer. These assays have not been well validated in a male cohort. The purpose of this study was to determine the current rates of genomic testing in male breast cancer (MBC), the distribution of risk of recurrence scores (RRS) in early stage MBC, and the effect of RRS on systemic treatment patterns. Methods: The National Cancer Database was queried and found to include 6,227 cases of pathologic T1/T2 and N0/N1 MBC from 2008-2014 with known genomic testing status. Of the 1478 (23.74%) male patients who had gene expression profiling performed, variables of interest included age at diagnosis, stage, estrogen receptor status (ER), RRS, and treatment. We compared the treatment patterns of the 1,343 patients who had RRS available and the 4,527 patients who were not tested. A similar analysis was performed in female breast cancer (FBC) patients to serve as a point of reference. Statistical analysis included multivariate logistic regression and Pearson's chi-square test. Results: Of the 1,478 (23.74%) cases of MBC who had gene expression profiling, the most significant variables included: younger age, non-Black race, diagnosis after 2010, tumor Grade II, Estrogen Receptor (ER) positivity, and N0 or N1mi disease. Of those who had results, the distribution of RRS was 59.3% low, 27.4% intermediate, and 13.3% high. A similar distribution was found in 154,705 women who were tested during the same study period. Risk scores in men were significantly associated with tumor grade and size, but not nodal status. 83.4% of men with a low RRS were treated with hormone therapy alone, with an adjusted odds ratio (AOR) of 7.18 (CI 5.78-8.91, p&amp;lt;0.001). Also, 61.8% of men with a high RRS received combination chemotherapy and hormone therapy, with an AOR of 5.16 (CI 3.60-740, p&amp;lt;0.001). Conclusion: Although there is limited literature supporting the use of genomic assays in MBC, our study found similar rates of testing in men and women with early stage breast cancer. Treatment patterns varied significantly based on risk stratification, implying that physicians are using gene profiling assays to help guide treatment in MBC. Understanding the role for genomic profiling in MBC is particularly important as these results will be incorporated into the new AJCC 8th edition staging system. Long term follow up is needed to determine whether these tests accurately predict prognosis and recurrence in a male cohort. Citation Format: Dubrovsky E, Raymond S, Chun J, Schnabel F. Gene expression profiling in male breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-03.

Occupational exposure to organic solvents and risk of male breast cancer: a European multicenter case-control study.

Objectives The etiology of male breast cancer (MBC) is largely unknown but a causal role of exposure to organic solvents has been suggested. Previous studies on occupational risk factors of breast cancer were often restricted to women who are frequently exposed to lower levels and at a lower frequency than men. We investigated the association between MBC and occupational exposure to petroleum and oxygenated and chlorinated solvents in a multicenter case-control study of rare cancers in Europe. Methods The study included 104 MBC cases and 1901 controls. Detailed lifetime work history was obtained during interviews, together with sociodemographic characteristics, medical history and lifestyle factors. Occupational exposures to solvents were estimated from a job-exposure matrix. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated using unconditional logistic regression models. Results Lifetime cumulative exposure to trichloroethylene >23.9 ppm years was associated with an increased MBC risk, compared to non-exposure [OR (95% CI): 2.1 (1.2-4.0); P trend <0.01). This increase in risk persisted when only exposures that occurred ≥10 years before diagnosis were considered. In addition, a possible role for benzene and ethylene glycol in MBC risk was suggested, but no exposure-response trend was observed. Conclusions These findings add to the evidence of an increased risk of breast cancer among men professionally exposed to trichloroethylene and possibly to benzene or ethylene glycol. Further studies should be conducted in populations with high level of exposure to confirm our results.

Androgen Expression &amp; Clinicopathological Features in Male Breast Cancer

Aim: To investigate prognostic features in male breast cancer (MBC). Methods: Clinicopathological information from 40 MBC patients was retrospectively reviewed. Androgen receptor (AR) and estrogen receptor (ER) were prospectively stained out in 22 cases and counted through software program analysis. Results: Median age was 65.5 years; most cases were Stage II (40%), Grade II (37.5%), ER ≥10% (72.5%) and PgR ≥10% (75%). AR &gt;10% was found in 17 of 22 cases. Although AR expression was correlated with ER, there are some cells without coexpression. Axillary node involvement was associated with DFS (p = 0.001) and age (p = 0.002) was associated with overall survival. Conclusion: ER is expressed in most MBC cases and is correlated with AR. Axillary involvement and age were associated with survival.

Male breast cancer: diagnosis stages, treatment and survival in a country with limited resources (Burkina Faso)

BackgroundMale breast cancer is a rare and less known disease. Therapeutic modalities affect survival. In Burkina Faso, male breast cancers are diagnosed in everyday practice, but the prognosis at short-, middle-, and long-term remains unknown. The objective of this study is to study the diagnosis stages, therapeutic modalities, and 5-year survival in male breast cancer at the General Surgery Unit of Yalgado Ouedraogo University Hospital from 1990 to 2009.MethodsA cohort longitudinal study concerning cases of breast cancer diagnosed in man. Survival was assessed using the Kaplan–Meier method and survival curves were compared through the LogRank test.ResultsFifty-one cases of male breast cancer were followed-up, i.e., 2.6% of all breast cancers. Stages III and IV represented 88% of cases. Eleven patients (21.6%) were at metastatic stage. Patients were operated in 60.8% of cases. The surgery included axillary dissection in 25 (80.6%) out of 31 cases. Lumpectomy was performed on 6.5% of patients (2 cases). Fifteen (29.4%) and 11 (21.6%) patients underwent chemotherapy and hormonal therapy, respectively. The FAC protocol was mostly used. Radiation therapy was possible in two cases. The median deadline for follow-up was 14.8 months. A local recurrence was noticed in 3.2% of cases. The overall 5-year survival rate was 49.9%. The median survival was over 5 years for stages I and II. It was 54 down to 36 months for stages III and IV.ConclusionDiagnosis is late. The lack of immunohistochemistry makes it difficult to define the proportion of their hormonal dependence. Surgery is the basic treatment. Five-year survival is slow and the median survival depends on the diagnosis stage. It can be improved through awareness-raising campaigns and the conduct of individual screening.

男性乳腺癌6例治疗体会

男性乳腺癌6例治疗体会

Preferential expression of NY-BR-1 and GATA-3 in male breast cancer

BackgroundMale breast cancer is an uncommon disease often discovered in advanced stage; thus, in the setting of metastatic adenocarcinoma, breast origin must be taken to account. Breast markers as NY-BR-1, GATA-3, mammaglobin, and BRST-2 are established tools for labelling primary and metastatic female breast cancer; however, none of them has been sufficiently studied in male breast cancer. The aim of this study was to analyze the expression of these markers in male breast cancer.Materials and methodsThirty consecutive cases of male breast cancer and eight loco-regional metastases were re-revaluated, assembled in tissue micro array (TMA), and stained with immunohistochemistry (IHC) for NY-BR-1, GATA-3, mammaglobin, and BRST-2. The IHC stains were scored either positive or negative. In addition, concordant expression patterns of primary tumors and matched metastasis were noted.Results30 of 30 (100%) primary tumors and 8 of 8 (100%) metastases were positive for NY-BR-1. 30 of 30 (100%) primary tumors and 6 of 8 (75%) metastases were positive for GATA-3. 22 of 30 (73.3%) primary tumors and 6 of 8 (75%) metastases were positive for Mammaglobin. 18 of 30 (60%) primary tumors and 5 of 8 (62.5%) metastases were positive for BRST-2. Differences in staining percentage were not significant with Fisher’s exact test.ConclusionWe found a high sensitivity for all the markers analyzed. Moreover, the expression of NY-BR-1 and GATA-3 seemed the most effective for labelling male breast cancer in primary and metastatic setting.