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

Male breast cancer (MBC) accounts for approximately 1% of all breast cancers and among these infiltrating lobular carcinomas (ILC) represents only 1-2% of all MBC cases. Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of ILC with only eight cases reported until now in males. Up to 10% of MBC cases have a germline pathogenic variant in a predisposing gene such as BRCA1 and BRCA2 genes. Mutations in PALB2 (partner and localizer of BRCA2) have been reported in men with breast cancer, with a frequency that ranges from 0.8 to 6.4%, but it has never been reported in male ILC. Here, we report a rare and interesting case of an invasive pleomorphic/solid lobular carcinoma, which carries a pathogenic variant in PALB2 gene, and a family history of breast cancer without other well defined risk factors for developing this type of neoplasia. In addition, we review the current literature.

Adjuvant tamoxifen adherence in men with early-stage breast cancer.

BACKGROUND: Most breast cancers (BCs) in men are hormone receptor-positive. Adjuvant tamoxifen is part of the standard treatment of these patients. Small, single-institution studies have suggested that men have high rates of discontinuing adjuvant endocrine treatment. The authors examined rates of tamoxifen discontinuation and medication adherence in a large population-based cohort of male patients with BC. METHODS: In the Surveillance, Epidemiology, and End Results-Medicare database, male patients with invasive nonmetastatic BC, diagnosed between 2007 and 2013, who were ≥65 years old, had Part D coverage, and had tamoxifen prescriptions within 1 year of diagnosis were identified. Adherence was defined as a medication possession ratio of ≥80% among those patients who were filling tamoxifen prescriptions. Logistic regression model was used to assess predictors of tamoxifen adherence. RESULTS: A total of 451 patients met eligibility criteria. The median age at diagnosis was 75 years. The median follow-up was 32.5 months. The rates of tamoxifen discontinuation were 15.8%, 24.3%, 31.3%, 36.9%, and 48.3% at 1, 2, 3, 4, and 5 years after diagnosis, respectively. Among the men who were still taking tamoxifen, the corresponding adherence rates were 76.9%, 73.6%, 68.7%, 64.8%, and 60.2%. In the adjusted model, significant predictors of lower adherence included residing in a high poverty area (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.28-2.12) and a Charlson comorbidity score of ≥2 (OR, 0.46; 95% CI, 0.22-0.97). CONCLUSION: Older men with breast cancer have high rates of tamoxifen discontinuation, with 48% of all patients discontinuing tamoxifen before the end of year 5. Additionally, even among those patients continuing tamoxifen, a substantial number of patients are nonadherent. Further research should evaluate potentially modifiable reasons for treatment discontinuation and lack of adherence to tamoxifen.

Identification of a new BRCA2 large genomic deletion associated with high risk male breast cancer.

BACKGROUND: Male breast cancer (MBC) is an uncommon disease that has been the focus of limited research. It is estimated that approximately 10% of men with breast cancer have a genetic predisposition, with BRCA2 being the most prevalent genetic mutation. Here we describe the case of MBC in a 64-year-old man who presented on physical examination a nodule in his left breast and declared to have an extensive family history of cancer. METHODS AND RESULTS: The patient was firstly diagnosed with an invasive ductal carcinoma (IDC) with histological grade III, nuclear grade 3, pT4N2Mx and positive for hormonal receptors and HER2. Exome sequencing was performed by massive parallel sequencing which had detected a novel BRCA2 germline mutation that is a large genomic deletion of 3,492 nucleotides including BRCA2 exon 14, and this deletion is out of frame and is predicted to lead to a stop codon in exon 15 at codon 2,496. CONCLUSION: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer. This is the first report of the mutation del3492 in BRCA2 exon 14, which leads to a truncated protein and therefore is clinically relevant. Mutation segregation analysis should be further done in the Brazilian population. Herein we highlight the importance of next-generation sequencing in the detection of large genomic deletions.

Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology.

Introduction: Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI). Methods: In this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples. Results and discussion: A total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy.

Male breast cancer with ureteral metastasis: a case report.

Breast cancer is rare in men and there is no report of male breast cancer (MBC) with ureteral metastasis. In this study, we report the first case of MBC with ureteral metastasis. A 60-year-old man was diagnosed with triple negative breast cancer (TNBC) with local lymph nodes metastasis (TNM stage: T4N3M0). After surgery, chemotherapy and radiotherapy he was diagnosed with ureter metastasis because of hematuria. This patient took a Precitype gene test (immune index and PAM50) after several lines of treatment and the result indicated that this was a Luminal A subtype case as well as HER-2 mRNA positive, which was quite different from his immunohistochemical staining. Because of his poor condition and he could not tolerate chemotherapy, we adjusted his therapeutic regimen with endocrine therapy and anti-HER-2 therapy according to the gene expression analysis with the informed consent of the patient and his families. However, it seemed that there was no obvious efficacy and he passed away five months later. In our opinion, MBC patients with urinary symptoms should be considered for the possibility of metastasis although urinary metastasis in breast cancer is rare. We still need more research about gene expression analysis and more evidence of treatment recommendations for MBC.

Prognostic significance of preoperative serum inflammation markers in patients with male breast cancer.

BACKGROUND: There were no predictive prognosis factors of serum in male breast cancer, while breast cancer is a heterogeneous disease. The purpose of our study was to determine the prognostic implications of the pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) in the serum of patients with male breast cancer. METHODS: We retrospectively identified a random cohort of male breast cancer patients treated at the Sun Yat-sen University Cancer Center between Jan 1, 1996 and Dec 31, 2016. A number of 108 patients had different inflammation markers recorded pre-operation. Survival status was retrieved from our cancer center registry and phone follow-up. Cox proportional hazards regression model was used to analyze the disease-free survival (DFS) and overall survival (OS). RESULTS: Among these patients in this study, 13 (12.0%) had disease recurrence, and 7 (6.5%) patients appeared distant metastasis. No statistically significant association of the preoperative NLR, PLR or LMR level with patients' different outcomes was found. CONCLUSIONS: In short, we were unable to establish a connection between preoperative inflammation biomarkers and male breast cancer patients' survival. Neither NLR, PLR nor LMR is useful for predicting prognosis in male breast cancer patients, and prospective studies to evaluate the above biomarkers as a simple prognostic trail is necessary.

The effect of metastasis patterns on survival in male patients with different breast cancer subtypes: results from the Surveillance, Epidemiology, and End Results (SEER) database.

BACKGROUND: Metastasis sites and breast cancer subtypes are important for breast cancer patients. This study aimed to assess possible relationships between them and their influence on prognosis in male breast cancer (MBC) patients. METHODS: We collected data on 2,983 patients with MBC from the Surveillance, Epidemiology, and End Results database, including 250 patients with M1 stage disease. Information on metastatic patterns was provided for bone, brain, liver, and lung metastases. MBC was classified into four subtypes: Her2-/HR+, Her2+/HR+, Her2+/HR-, and triple negative (TN). Univariate and multivariate logistic regression analysis were used to analyze the association, and Cox regression analyses were used to analyze prognosis. RESULTS: The bone was the most common metastatic site and the brain was the least common metastatic site. Patients with the Her2-/HR+ subtype had the highest proportion of metastatic disease, and Her2+/HR- patients had the lowest proportion. Univariate and multivariate logistic regression analyses showed that there were significant differences in distant metastasis patterns in patients with different subtypes. Men with the Her2+/HR+ or Her2-/HR+ subtypes with bone metastasis had better cancer specific survival (CSS), and those with the TN subtype had the worst CSS in all metastatic patterns. CONCLUSIONS: MBC subtypes are associated with different metastasis patterns and can have different effects on prognosis. This study might provide insights into a better understanding of MBC.

Incidence and survival outcomes of early male breast cancer: a population-based comparison with early female breast cancer.

BACKGROUND: Male breast cancer (MBC) is a rare malignancy. We aimed to analyze the incidence trends, clinicopathological characteristics, and survival outcomes in early MBC comparison with early female breast cancer (FBC). METHODS: We included eligible MBC and FBC patients with stage I-II disease in the Surveillance, Epidemiology, and End Results (SEER) database from 2000-2015. Joinpoint regression was used to evaluate the trends in age-adjusted incidence. A one-to-four propensity score matching (PSM) analysis was performed to reduce bias in a retrospective study. Survival outcomes were evaluated using Kaplan-Meier analyses with the log-rank test and Cox proportional hazards regression analysis. RESULTS: Trends in the age-adjusted incidence rates of early MBC were stable [2000-2015, annual percentage change (APC) =0.50, 95% confidence interval (CI): -0.1 to 1.1, P=0.102]; however, the incidence of early FBC changed significantly over the time period (2000-2015, APC = 0.30, 95% CI: 0.0 to 0.6, P=0.045). In the matched cohort, unmarried status, higher grade, larger tumor size, and advanced lymph node (LN) status were associated with a higher risk of breast cancer death and death of any causes both in early MBC and FBC patients. The hormone receptor (HR) status was as a prognostic factor in FBC patients, but not in MBC. Early MBC had worse breast cancer-specific survival (BCSS) and overall survival (OS) than early FBC in stage I, stage II and HR-positive subgroup of patients. CONCLUSIONS: The biological behavior, clinicopathological features, and clinical outcomes of early MBC are different from that of FBC. Further studies on individualized treatment approaches in MBC are needed.

Social Support of Male Breast Cancer Patients-a Mixed-Methods Analysis.

The aim of this study is to explore the social support of male breast cancer patients (MBCP) in Germany. In particular, three aspects of social support focus on (a) the used resources within the social environment, (b) the received support, and (c) the differences of used social support between MBCP. A mixed-methods design is applied including data of qualitative interviews (N = 27 MBCP) and a written questionnaire (N = 100 MBCP). MBCP use different resources of support from their social environment like partners, family, friends, colleagues, other breast cancer patients, and medical experts. Mostly, MBCP receive emotional and informational support. They often receive emotional support from their partners and informational support from medical experts. Different types of social support usage can be identified dependent on age, occupation, and severity of disease. The older the patients and the less the disease severity, the less social support MBCP use. Within cancer care, partners and the closer social environment should be included more as they are a key resource for MBCP. As health-care professions might also be an important resource of support for MBCP, further research should examine this resource.

Current state of surgical management for male breast cancer.

Management guidelines for male breast cancer have long been extrapolated from those for female breast cancer, which are based on large, randomised-controlled trials. While there are no randomised-controlled trials for male breast cancer management mainly due to the rarity of the disease, the only type of evidence available comes from retrospective studies, subject to selection biases and small sample sizes. Male breast cancer, while similar to female breast cancer in many respects, has some important differences that can affect management choices. Most cancers are oestrogen and progesterone receptor positive, and usually more advanced at presentation than female breast cancer. This is likely due to less breast parenchyma in male patients and delay to diagnosis. The classical management option for male patients with breast cancer is mastectomy, due to small tumour-to-breast ratio and often central position of the tumour. Breast conserving surgery is still useful in selected cases and has similar outcomes when compared to mastectomies in these patients. For patients with clinically negative lymph nodes, sentinel lymph node biopsy offers the same prognosis as axillary lymph node dissection, but with less associated morbidity. Endocrine therapy is of particular use, due to high levels of receptor positivity. Adjuvant endocrine therapy seems to significantly improve overall survival of male patients with breast cancer and while no prospective evidence exists for neoadjuvant hormonal therapy, there is hope that this is a useful management option as well. Radiotherapy is also useful in an adjuvant setting, particularly when combined with endocrine therapy. Better identification of patients, less delay from presentation to diagnosis and more collaborative efforts are key in improving the management, prognosis and outcomes of patients with male breast cancer.