Factors In Male Breast Cancer Research Articles

Invasive micropapillary type male breast cancer: a case report

Male breast cancer is rarely seen and peaks at the age of 71. Hyperestrogenism, gonadal dysfunction, obesity, and alcohol are among the risk factors for male breast cancer. In hereditary cases, BRCA2 mutation is often observed. The most common symptom is a painless mass that is palpable behind the nipple. Most male breast cancers are ductal carcinomas (81%), papillary carcinomas (13%), and mucinous carcinomas (6%). The invasive micropapillary carcinoma of the breast is important due to its high rate of lymphnode metastasis, recurrence, and distant metastasis. Mortality is 50% higher in men with lymphnode involvement compared to non-involved cases. Furthermore, as the number of affected lymphnodes increases, the prognos is worsens. In this study, we examined a case of invasive micropapillary type male breast cancer with clinical presentation as a palpable mass, lymphnode involvement, and aimed to highlight the radiological considerations that need attention.

Male Breast Cancer: An Updated Review of Patient Characteristics, Genetics, and Outcome.

Male breast cancer (MBC) is a rare entity, underrepresented in population studies and clinical trials, resulting in management of MBC to be informed by current research on female breast cancer (FBC). A literature review was conducted by accessing relevant articles on 2 databases, by searching keywords "male breast cancer". A total of 29 articles from year 2011 to 2022 were selected for this review. The authors found that male breast cancer generally occurs later in life with higher stage, higher grade, and more estrogen receptor (ER) positive tumours. Most of the studies noted the mean age for MBCs at the time of presentation as >60 years. Risk factors for male breast cancer include family history, obesity, lower physical activity, and syndromes like the Klinefelter syndrome. Positive family history is much higher in MBC compared to FBC (30.9 vs. 18.4%). BRCA 2 cancers constitute a higher proportion compared to FBCs. A lot of genetic mutations have been observed. Some show promise to assess disease-specific survival and proliferative rate like TWIST1 and RUNX3, among others. MBCs usually present with a palpable lump in central region, with a bigger size and chance of nodal involvement and metastasis compared to FBCs. They are mostly infiltrating ductal type and hormone receptor positive, with worse histological grade. Treatment usually follows the same principles as FBCs (systemic therapy, surgical excision, and radiotherapy), with poorer prognosis to same treatment approach, possibly owing to its advanced stage at presentation. This is a rare entity which requires further research to ascertain need for different management approach than FBCs.

Male Breast Cancer – Experience at a Tertiary Care Center in India

Introduction: Male breast cancer (MBC) is a rare affliction accounting for approximately 1% of all breast cancer cases. The treatment guidelines of MBC mirror those of female breast cancer which are derived mostly from data obtained from studies involving female breast cancer patients. Data on MBC are mostly limited to single-institution studies due to the rarity of the disease. This study was undertaken to assess retrospectively the pattern of demographic and clinicopathological factors in MBC treated at our tertiary care center. Materials and Methods: Records of MBC treated between January 2019 and December 2020 in our institute were analyzed and data regarding the demographic and clinicopathological profile of patients was recorded. Observational retrospective single centre study. Results: A total of 12 patients of MBC were encountered with a median age of 58 years. The painless lump was the most common presentation with the retro-areolar region being the most commonly involved site. The most common American Joint Committee on Cancer anatomical stage group observed was Stage II with the left breast being involved more than the right. None of the patients had a family history of breast carcinoma. Out of the 12 patients, 10 patients were positive for hormonal receptors, whereas only two patients showed human epidermal growth factor receptor 2 amplifications. Conclusion: MBC is a rare disease. Further multi-institutional studies involving a larger number of patients are needed for a better understanding and formulation of gender-specific guidelines for the effective management of MBC.

An Update on the General Features of Breast Cancer in Male Patients-A Literature Review.

Male breast cancers are uncommon, as men account for less than 1 percent of all breast carcinomas. Among the predisposing risk factors for male breast cancer, the following appear to be significant: (a) breast/chest radiation exposure, (b) estrogen use, diseases associated with hyper-estrogenism, such as cirrhosis or Klinefelter syndrome, and (c) family health history. Furthermore, there are clear familial tendencies, with a higher incidence among men who have a large number of female relatives with breast cancer and (d) major inheritance susceptibility. Moreover, in families with BRCA mutations, there is an increased risk of male breast cancer, although the risk appears to be greater with inherited BRCA2 mutations than with inherited BRCA1 mutations. Due to diagnostic delays, male breast cancer is more likely to present at an advanced stage. A core biopsy or a fine needle aspiration must be performed to confirm suspicious findings. Infiltrating ductal cancer is the most prevalent form of male breast cancer, while invasive lobular carcinoma is extremely uncommon. Male breast cancer is almost always positive for hormone receptors. A worse prognosis is associated with a more advanced stage at diagnosis for men with breast cancer. Randomized controlled trials which recruit both female and male patients should be developed in order to gain more consistent data on the optimal clinical approach.

Top 100 cited articles in male breast cancer: Abibliometric analysis.

Male breast cancer is a considerably rare condition and only accounts for 1% of all breast cancer cases. Due to limited public awareness, the condition is likely to present late, leading to late diagnosis and treatment worsening morbidity and mortality. This article aims to identify the focus and most influential research on male breast cancer. Objective Identify the most influential papers in male breast cancer. Search on Web of Science using the search terms 'Male', 'Breast Cancer' and "Male breast cancer" to identify all full manuscripts in English language and were ranked by the total number of citations. The top 100 articles were then further analysed according to subject, author, journal, year and country of publications. The mean number of citations per paper was 96. Most cited paper was by Thorlacius, S etal.evaluating the relationship between BRCA2 and female breast cancer, prostate cancer, pancreatic cancer and ovarian cancer. Cancer is the journal with the most published papers and received most citations in the male breast cancer research field. The USA contributed 49 of the manuscripts in the top 100. The most studied topic was risk factors for male breast cancer, with 20 articles. The most cited papers identified in this study described the advance in the knowledge of genetics and epidemiology in male breast cancer and has led to improvements in the 4 management of the disease. Most of the highly cited articles in this field were published in high impact journals and had accumulated at least 100 citations to date, reflecting their quality and impact. By collating the most influential publications in this field, this analysis can serve to identify knowledge gaps in male breast cancer research as well as to help identify what makes a paper impactful and citable.

Abstract PS8-40: Penetrance of male breast cancer susceptibility genes: A systematic review

Abstract Background: Family history is one of the strongest predisposing factors for male breast cancer (MBC). Several MBC susceptibility genes have been identified, but the risk of MBC for individuals with a pathogenic variant in these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes. Methods: A search query was developed to identify MBC-related abstracts indexed in PubMed, with the followings structure: "Breast Neoplasms, Male"[Mesh] OR (((“Men”[MESH]) OR (male*[TIAB]) OR (man[TIAB]) OR (men[TIAB])) AND ((“Breast Neoplasms”[MESH]) OR (Breast Cancer*[TIAB]) OR (Breast neoplasm*[TIAB]))). A validated natural language processing (NLP) method was applied to retrieve and classify abstracts reporting penetrance estimates. Abstracts labeled as relevant were manually reviewed. The full-text papers of identified penetrance studies were then annotated to extract MBC risk data. These penetrance studies’ bibliographies were also reviewed to ensure comprehensiveness. Results: We identified 17 penetrance studies from 11,799 abstracts, covering five MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2 (Table 1). 53% of these studies were case-control studies, while the rest were cohort studies. Odds ratio (OR), cumulative risk (CR), and relative risk (RR) were three commonly reported risk measures. For BRCA2, eight out of nine studies reported significantly increased risk of MBC or a lifetime CR of over 6%; only one study reported an increased but not statistically significant risk. For BRCA1, one out of six studies reported an elevated lifetime CR of 5.8%, while a second reported a minor increase (OR=1.49) that was statistically significant. The risks reported in the remaining four studies showed no statistically significant increase in risk. Seven studies reported the penetrance of CHEK2, but the risks diverge between the variants tested (Table 2). All three PALB2 studies reported significantly increased risk, while only one ATM study reported an increased risk of MBC, which did not reach statistical significance. Conclusion: To our knowledge, this review provides the first complete set of reported penetrance data for five MBC susceptibility genes. Contradictory MBC risks (significantly increased risk vs. risks that were not statistically significant) were common, which may be due to the studies’ different ascertainment criteria resulting in risk estimates for differing populations. Risk across these studies cannot be directly compared unless studies adjust for ascertainment, though this cataloging of risk defines our current understanding. Table 1: MBC penetrance studiesGeneNumber of StudiesStudy TypeRisk Estimate ReportedMBC RiskBRCA296 Cohort, 3 Case-controlOR, RR, CRStatistically significant increased risk (or lifetime CR > 6%) in 8/9 studiesCHEK277 Case-controlOR, RRVarying risk by variantBRCA163 Cohort, 3 Case-controlOR, RR, CR, HRStatistically significant increased risk in 1/6 studies, one study report lifetime CR = 5.8%PALB231 Cohort, 2 Case-controlOR, RRStatistically significant increased risk in 3/3 studiesATM11 Case-controlORStatistically significant increased risk in 0/1 studyOR: odds ratio; RR: relative risk; CR: cumulative risk; HR: hazard ratio Table 2: As an example: Reported penetrance of CHEK2 for male breast cancer in studies with varying ascertainment criteriaFirst Author, Year of Publication, Patient Population*Pathogenic VariantNumber of CarriersRisk TypeRisk Estimate (95% CI)Statistical SignificanceMeijers-Heijboer H, 2002, Multiple Countries1100delC57RR10.28 (3.54-29.87)YesSyrjakoski K, 2004, Finland1100delC28OR1.27 (0.04-7.92)NoWasielewski M, 2009, Netherlands1100delC21OR4.1 (1.2-14.3)YesPritzlaff M, 2017, USAAll441OR2.4 (1.4-3.9)Yes1100delC135OR3.8 (1.7-7.8)YesI157T238OR1.3 (0.5-3.0)NoHallamies S, 2017, Finland1100delC30OR4.47 (1.51-13.18)YesI157T104OR1.12 (0.4-3.13)NoLu HM, 2019, USANot specifiedNot specifiedOR1.66 (0.04-10.34)NoKleiblova P, 2019, Czech RepublicTruncations3OR20.21 (3.5-80.0)YesDeleterious missense1OR11.87 (0.25-100.83)NoIntermediate missense2OR1.3 (0.15-5.07)NoNeutral missense2OR9.07 (0.98-40.41)NoOR: odds ratio; RR: relative risk* All studies in Table 2 are case-control studies Citation Format: Reem S Chamseddine, Jin Wang, Kanhua Yin, Preeti Singh, Jingan Zhou, Danielle Braun, Mark E Robson, Kevin S Hughes. Penetrance of male breast cancer susceptibility genes: A systematic review [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-40.

Prognostic Factors in Male Breast Cancer: A Retrospective Nationwide Study in South Korea by the Study of SMARTSHIP Group.

This study evaluated the incidence, the survival outcomes and its prognostic factors for male breast cancer (MBC) in Korea. Using the National Health Insurance Service database of Korea, we identified MBC patients who had the new claim code of C50. Medical records including type of surgeries and radiotherapy within one year of the first claim and death records were reviewed. Between 2005 and 2016, 838 newly diagnosed MBC patients were included (median follow-up, 1,769 days). The 70–74-year age group had the highest incidence of MBC. The 5-year survival rate was 73.7%. Age > 65 years, low income, no surgical intervention, no tamoxifen use, and > 2 comorbidities correlated with a worse outcome. MBC incidence has increased over time, and its peak is noted at age > 70 years. Age > 65 years, > 2 comorbidities, no surgical intervention, and no tamoxifen use correlate to poor prognosis.

Prognostic Factors in Male Breast Cancer: A Single Centre Experience.

To determine the prognostic factors by assessing the clinicopathological characteristics of the male patients with breast cancer (MBC). Observational study. Department of Internal Medicine, HSU Dr. Abdurrahman Yurtaslan Oncology, Training and Research Hospital, Turkey, between January 2010 and November 2018. Data of patients with MBC were evaluated. Age ≥18 years, diagnosis of breast carcinoma, and male gender were the inclusion criteria of the study. Patients were excluded from the study, if their data were incomplete. Ki-67, the status of estrogen receptor (ER), progesterone receptor (PR), and HER2 receptor were obtained from the hospital records. Kaplan-Meier method was performed for survival analysis. Cox regression analysis was used to determine independent prognostic factors of overall survivall (OS). Out of the 73 patients included in the study, 37 of them aged under 65, while 36 of them aged 65 or over. ER positivity was 94.5%, while PR positivity was 87.7%, and HER2 positivity was 13.7%. It was found that as a result of the univariate analysis, the 5-year OS of the elderly group (≥65 years) was lower compared to the younger group (<65 years, 74.2% vs. 93.3%, p=0.022). Age, tumor grade, and T stage were included in the multivariate Cox regression analysis and only advanced age was found to be an independent poor prognostic factor (HR: 3.068, 95% CI: 1.013-9.293, p=0.047). Advanced age might be an independent poor prognostic factor for patients with MBC. Key Words: Breast cancer, Elderly, Male, Prognosis.

Assessment of Prognostic and Therapeutic Factors in Male Breast Cancer: An Observational Study of a Southwest Spanish Single Center

Background: Male breast cancer (MBC) accounts for less than 1% of breast cancer, requiring extrapolation of results from studies in women. The aim of the study is to evaluate prognostic and therapeutic factors with special focus in endocrine treatment (ET) on the disease outcome.Methods: Observational, retrospective, single-center study of 53 MBC treated between January 1997 and December 2018 participated in the study. Among the participants, 48 patients had a performance status (PS) 0-1 (91%), 48 were hormone-receptor-positive (91%) and 4 were human epidermal growth factor 2 receptor (HER2) positive (8%). A total of 45 patients (85%) were treated with ET, with 36 patients (68%) receiving treatment in an adjuvant setting. The association analysis was performed using Chi-square test and survival was estimated using Kaplan-Meier with SPSS v25. Results: The cohort had a median age of 68 years old (range: 40-88). We found that 84% had a non-metastatic breast cancer. A breast cancer gene (BRCA) analysis was carried out in 43% of the patients, showing BRCA2 mutated in 26.1% of those analyzed, without obtaining a benefit in overall survival (P=0.698). The analysis showed higher 5-year overall survival (OS) for PS 0 (P=0.010), absence of vascular invasion (P=0.033), Ki67 ?14% (P=0.041) and absence of metastasis at diagnosis (p&lt;0.0001). Patients receiving adjuvant ET above 5 years had a longer median OS (89 vs 69.6 months, P=0.024), disease-free survival (DFS), and distant relapse (84 vs 48 months; P=0.005, and P=0.002, respectively).Conclusions: Several prognostic factors for male breast cancer have been described. Noteworthy, patients receiving adjuvant ET above 5 years had a higher OS and DFS. BRCA did not show prognostic value in OS in this cohort. Further studies with larger sample size are necessary.

32P Clinicopathologic features and prognostic factors in male breast cancer: A single centre experience

32P Clinicopathologic features and prognostic factors in male breast cancer: A single centre experience

Epidemiology of male breast cancer

BackgroundDue to its rarity, few studies have characterized the epidemiology of male breast cancer. The purpose of this study was to determine survival and risk factors for male breast cancer in a large U.S. population. MethodsIn this study, 19,795 male patients with breast cancer were identified from the National Cancer Database (2004–2014). Patient demographics, tumor characteristics and treatments were analyzed by using descriptive statistics. We used multivariate Cox regression and Kaplan Meier analysis. ResultsOver 10 years, the incidence of male breast cancer increased from 7.2% to 10.3%, while mortality decreased from 11% to 3.8%. Socioeconomic factors predicting mortality included income medium, and high vs low (HR = 0.78; 0.68), private vs no insurance (HR = 0.73) and the academic research facility vs community cancer center (HR = 0.79). Significant predictors of all-cause mortality included age (HR = 1.04), tumor size (HR = 1.01), hormone receptor expression (HR = 0.8) and cancer stage I vs II, III, and IV at the time of diagnosis (HR = 1.5, 2.7, 4.4, 9.9 respectively). Other predictors of mortality include surgery (HR = 0.4), chemotherapy (HR = 0.8), radiation (HR = 0.8), and hormonal therapy (HR-0.8). ConclusionsSocioeconomic factors, cancer stage, tumor characteristics (size and grade), and high Charlson-Dayo score contributed to higher mortality among male patients diagnosed with breast cancer. Surgery was most effective, followed by radiation, chemotherapy, and hormonal therapy. Patients with positive ER or PR expression demonstrated better survival. Adjusting for socioeconomic factors, biomarker identification and timely, appropriately chosen treatment are likely to reduce the risk for mortality.

Prognostic Value of the Neutrophil-Lymphocyte, Platelet-Lymphocyte, and Monocyte-Lymphocyte Ratios in Male Breast Cancer Patients

Background: The aim of the present study was to assess the blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) as prognostic factors in male breast cancer (BC) patients. Methods: A retrospective analysis of 38 male BC patients who were treated at the Institute of Oncology (Gliwice, Poland) between January 2005 and December 2018 was performed. The prognostic value (in terms of overall survival [OS]) of the pretreatment PLR, NLR, and MLR was assessed by univariate analysis. Results: We observed a tendency towards worse OS among male BC patients with lymph node metastases (N+) (5-year OS: 43.5 vs. 73.9%; p = 0.087), a greater tumor size (T4 vs. T1 + T2) (42.0 vs. 70.5%; p = 0.061), and a negative steroid receptor status (PR–) (28.6 vs. 65.6%; p = 0.109). Patients with a family history of cancer had significantly better 5-year OS than patients without a family history of cancer (86.3 vs. 35.0%; p = 0.001). Younger male BC patients (age ≤56 years) had better 5-year OS than patients >56 years of age (82.5 vs. 42.3%; p = 0.028). The 5-year OS was lower among patients with a lower lymphocyte value (≤1.82 × 10³) (29.0 vs. 75.6%; p = 0.010). There was a tendency towards worse OS among patients with a higher platelet count (>281 × 10³) (4.5-year OS: 16.7 vs. 65.8%; p = 0.056). The 5-year OS was insignificantly lower in the group with NLRs >2.74 than in the group with NLRs ≤2.74 (37.5 vs. 62.8%; p = 0.078). A worse OS rate was associated with an elevated PLR (>169.1) (22.2 vs. 70.1%; p = 0.008). Similarly, there was worse OS in the group with higher MLR (>0.30) (41.8 vs. 78.3%; p = 0.025). Conclusions: The present results reveal that elevated MLRs (>0.30) and PLRs (>169.1) are associated with poor OS among male BC patients. Similarly, but insignificantly, an elevated NLR (>2.74) affected OS.

High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer

BackgroundBreast cancer is rare in men, but management is focused on tumor characteristics commonly found in female breast cancer. The tumor microenvironment of male breast cancer is less well understood, and insight may improve male breast cancer management. The hepatocyte growth factor (HGF)/c-MET axis and the stromal cell-derived factor-1 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis are prognostic in women with breast cancer. We aimed to investigate these factors in male breast cancer and correlate them with patient survival.MethodsFrom 841 Dutch males with breast cancer who were enrolled in the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program (NCT01101425) and diagnosed between 1990 and 2010, archival primary tumor samples were collected. Tissue microarrays were constructed with 3 cores per sample and used for immunohistochemical analysis of HGF, c-MET, CXCL12, and CXCR4. Overall survival (OS) of the patients without metastases (M0) was analyzed using the Kaplan-Meier method. The value of the markers regarding OS was determined using univariable and multivariable Cox regression analyses, providing hazard ratios (HRs) and 95% confidence intervals (95% CIs).ResultsOf 720 out of 841 patients, sufficient tissue was available for analysis; 487 out of 720 patients had M0 disease. Patients with high HGF expression and high CXCL12 expression had a superior OS (low vs high expression of both markers, 7.5 vs 13.0 years, hazard ratio [HR] 0.64, 95% CI 0.49–0.84, P = 0.001 [HGF]; 9.1 vs 15.3 years, HR 0.63, 95% CI 0.45–0.87, P = 0.005 [CXCL12]). Multivariate analysis identified HGF as an independent predictor for OS (HR 0.64, 95% CI 0.47–0.88, P = 0.001).ConclusionsHGF and CXCL12 tumor expression appear to identify male breast cancer patients with a relatively good prognosis. Possibly, this could support male breast cancer-specific management strategies in the future.

1187P - Clinical implication of PDL1 expression and TILs in male breast cancer: More hype or new hope? Results from the UMBREAC trial (NCT03240510)

Background: Whether PDL1 or TILs have any indication for prognosis in male breast cancer (MBC) patients remains unknown. In this study, we investigated the relationship between the expression and degree of PDL1 and TILs and evaluated the prognostic value of these factors in MBC. Methods: We retrospectively identified 150 MBC patients diagnosed between 2003 and 2013 at Salah Azaïz Cancer Institute. PDL1, Stromal (str) CD8+ and CD4+ TILs were evaluated immunohistochemically. TILs levels were evaluated following 2014 International TILs Working Group guidelines. Results: Fifty three percent of MBC patients had low str-TILs and 47% had moderate str-TILs. No lymphocyte predominant breast cancer was identified. Only 12% of MBC patients had high str-CD8+TILs and 11% had high str-CD4+TILs. TNBC subtype and HER2 enriched tumors had higher median levels of str-CD8+TILs, str-CD4+ TILs and str-TILs at diagnosis. On univariate analysis, higher levels of str-CD8+TILs, str-CD4+ TILs and str-TILs were associated with better OS (p = 0.035, p = 0.043 and p = 0.040 respectively). Multivariate analysis identified str-CD8+ TILs and str-TILs as independent prognostic factors for OS ([HR = 0.851 (0.706-0.997), p = 0.000] and [HR = 0.69 (0.43-0.96), p = 0.045] respectively). High expression of PD-L1 was observed in 64.5% of MBC samples. Patients with high PD-L1 expression had significantly shorter overall survival (OS) than patients with low expression (p = 0.002, hazard ratio HR = 5 [2.624 –10.642]). Multivariate analysis identified PD-L1 as independent prognostic factor for OS (p < 0.001, HR = 0.775 [0.680–0.870]). Conclusions: PD-L1 expression, Str-CD8+ T cells and str-TILs represents promising novel biomarkers with prognostic significance in MBC. Thus, successful inclusion of these markers in prognostic clinical models is becoming a realistic hope in MBC. Clinical trial identification: NCT03240510. Legal entity responsible for the study: Institut Salah Azaïz. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Prognostic factors for male breast cancer: A breast center’s 10-year experience

Prognostic factors for male breast cancer: A breast center’s 10-year experience

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 P5-23-01: Clinical and biological characterization of male breast cancer (BC) EORTC 10085/TBCRC 029/BOOG 2013-02/BIG 2-07: Baseline results from the prospective registry

Abstract BACKGROUND: Through the International Male Breast Cancer Program, a prospective registry for male BC was created with the goals of evaluating 1) the clinical and biological features of this disease and 2) assessing feasibility of a prospective therapeutic clinical trial. METHODS: All men, with any stage histologically proven invasive breast cancer, age 3 18 years, and newly presenting at the participating institutions (within 3 months prior) were eligible. Patients were enrolled for 30 months after activation of the first center, through February 2017. Per the study design, if &amp;lt;100 men enrolled, the study would be considered a failure and therapeutic trials would not be pursued through this network. Epidemiologic data, staging, pathologic features, and BRCA status were collected. Treatment and outcome data collection is ongoing. Optional collection of FFPE tumor samples, blood, and QOL were performed in the US, the Netherlands, and Latin America. Clinical database lock for this report was May 30, 2017. We currently report patient and disease characteristics and will update with patterns of treatment for the presentation. Outcomes and biological samples will be analyzed in the future. RESULTS: 557 patients were enrolled: 75% in Europe, 20% in United States, 5% in other countries. 6.3% of patients had missing forms. Median age was 67 years (range 26-92). 93% were diagnosed 2010-2017. Among patients with complete data, 79% presented with a breast mass. 88% were M0 and 12% M1. Among M0 patients: 47%, 39%, 2%, and 11% had T1, T2, T3, and T4 disease respectively; 52% were N0. Overall, 98% had ER+ disease and 11% had HER2+ cancer. 14% had grade 1, 56% had grade 2, and 30% had grade 3 tumors. Among 112 men who underwent BRCA1 testing, 1 was positive. Among 118 men who had BRCA2 testing, 18 (15%) were positive. 21% of men had prior or concurrent malignancies, with the following most common sites: prostate, non-melanoma skin, colorectal, and melanoma. The prevalence of previously identified possible risk factors for male breast cancer were: overweight/obesity (72%), former/current smoker (51%), current alcohol 31 drink daily (41%), family history of breast cancer (35%), gynecomastia (16%), history radiation exposure (8%), use of anti-androgens (1%), and use of estrogens (1%). CONCLUSION: Through an international collaborative effort, we were able to prospectively accrue 557 patients to a male breast cancer registry. These results demonstrate feasibility of pursuing a therapeutic clinical trial in men with breast cancer. In addition, this study shows the relatively low uptake of BRCA testing, high rates of concurrent/prior malignancy, and the rates of potentially modifiable risk factors in this patient population. Funding from Breast Cancer Research Foundation, Susan G. Komen, Dutch Pink Ribbon Foundation, Swedish Breast Cancer Association (BRO) and EBCC Council. Citation Format: Giordano SH, Schröder CP, Poncet C, van Leeuwen-Stok E, Linderholm B, Abreu MH, Rubio I, Van Poznak C, Morganstern D, Cameron D, Vleugel MM, Smilde TJ, Bozovic-Spasojevic I, Korde L, Russell NS, den Hoed IDM, Honkoop AH, van der Velden AWG, van 't Riet M, Dijkstra N, Bogler O, Goulioti T, Hilsenbeck S, Ruddy KJ, Wolff A, van Deurzen CHM, Martens J, Bartlett JMS, Aalders K, Tryfonidis K, Cardoso F. Clinical and biological characterization of male breast cancer (BC) EORTC 10085/TBCRC 029/BOOG 2013-02/BIG 2-07: Baseline results from the prospective registry [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 P5-23-01.

CHEK2 c.1100delC mutation is associated with an increased risk for male breast cancer in Finnish patient population

BackgroundSeveral susceptibility genes have been established for female breast cancer, of which mutations in BRCA1 and especially in BRCA2 are also known risk factors for male breast cancer (MBC). The role of other breast cancer genes in MBC is less well understood.MethodsIn this study, we have genotyped 68 MBC patients for the known breast or ovarian cancer associated mutations in the Finnish population in CHEK2, PALB2, RAD51C, RAD51D, and FANCM genes.ResultsCHEK2 c.1100delC mutation was found in 4 patients (5.9%), which is significantly more frequent than in the control population (OR: 4.47, 95% CI 1.51–13.18, p = 0.019). Four CHEK2 I157T variants were also detected, but the frequency did not significantly differ from population controls (p = 0.781). No RAD51C, RAD51D, PALB2, or FANCM mutations were found.ConclusionsThese data suggest that the CHEK2 c.1100delC mutation is associated with an increased risk for MBC in the Finnish population.

Abstract P3-15-01: Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs), CD4+ TILs and TILs in male breast cancer

Abstract Background Several studies have demonstrated that the presence and the amount of tumor-infiltrating lymphocytes (TILs) are a potential biomarker of prognostic significance in some solid tumors. Data suggests that high levels of TILs are associated with favorable prognosis. However, whether TILs have any indication for prognosis in male breast cancer (MBC) patients remains unknown. In this study, we investigated the relationship between the expression and degree of CD8+ TILs, CD4+ TILs, and TILs and evaluated the prognostic value of these three factors in MBC. Methods We retrospectively identified 110 male breast cancer patients diagnosed between 2000 and 2013 at Salah Azaïz Cancer Institute. Stromal (str) CD8+ and CD4+ TILs were evaluated immunohistochemically. Two pathologists independently evaluated TILs levels using H&amp;E stained slides following 2014 International TILs Working Group guidelines. Kaplan Meier and univariate and multivariate Cox regression analysis were applied to determine the association of CD8+ TILs, CD4+ TILs and TILs with clinicopathological features and overall survival (OS). Results The median for presence of str-CD8+TILs was 7% (0%-40%), str-CD4+TILs was 2% (0%-20%) and str-TILs was 10% (1%-40%). Only 12% of MBC patients had high str-CD8+TILs and 11% had high str-CD4+TILs. Fifty three percent had low str-TILs and 47% had moderate str-TILs. No lymphocyte predominant breast cancer was identified. Regarding intrinsic molecular subtypes, TNBC subtype and HER2 enriched tumors compared with Hormone receptor positive tumors had higher median levels of str-CD8+TILs, str-CD4+ TILs and str-TILs at diagnosis. However, increased level of str-CD8+ TILs, str-CD4+TILs and str-TILs weren't associated with improved OS in IHC subtypes (p=0.597, p=0.498 and p=0.456 respectively). On univariate analysis, higher levels of str-CD8+TILs, str-CD4+ TILs and str-TILs were associated with better OS (p=0.035, p=0.043 and p=0.040 respectively). Multivariate analysis identified str-CD8+ TILs and str-TILs as independent prognostic factors for OS ([HR= 0.851 (0.706-0.997), p=0.000] and [HR= 0.69 (0.43-0.96), p=0.045] respectively) but not str-CD4+ TILs (p=0.276). A high level of str-TILs was correlated with high str-CD8+ (p = 0.025). Conclusion The level of TILs in male breast cancer is low, suggesting prominent immune regulation/suppression in this disease. Str-CD8+ T cells and str-TILs represent potential prognostic markers in male breast cancer patients. Citation Format: Abdeljaoued S, Bettaieb I, Adouni O, Goucha A, Ghozzi R, Bouzaiene H, Hdiden M, Ben Hassouna J, Makhlouf R, El Benna F, Boussen H, Rahal K, Gamoudi A. Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs), CD4+ TILs and TILs in male breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-15-01.

Prognostic factors for male breast cancer: A breast unit's 10-year experience

Prognostic factors for male breast cancer: A breast unit's 10-year experience