Tumor Microenvironment in Male Breast Carcinoma with Emphasis on Tumor Infiltrating Lymphocytes and PD-L1 Expression.

Male breast cancer (MBC) is rare and usually presents as a locally advanced disease. Stromal tumor-infiltrating lymphocytes (sTILs) are associated with a better response to neoadjuvant chemotherapy and improved prognosis in all molecular subtypes of female breast cancer, but their role in MBC is less clear. We studied sTILs and the expression of programmed cell death ligand 1 (PD-L1) and pan-TRK in MBC. We retrospectively studied 113 cases of MBC surgically treated between 1988 and 2015. The tumors were evaluated for histological type and grade, stage, intrinsic subtype and sTILs. We performed immunohistochemistry for PD-L1 (clone SP142) and pan-TRK (clone EPR17341) on tissue microarrays. Pan-TRK positive cases were further analyzed by next-generation sequencing. The median age was 69 years (range 60−77). Invasive carcinoma of no special type was found in 94.7% of cases, of which 53.1% were grade 2. Estrogen receptor was positive in 92% of the tumors, progesterone receptor in 85.8%, androgen receptor in 70.8%; 4.4% were human epidermal growth factor receptor 2 (HER2)-positive, and 55.8% HER2-low. 40.7% of tumors were luminal A and 51.3% luminal B, 4.4% HER2-enriched and 3.5% triple negative carcinoma. sTILs density was <50% in 96.4% of the tumors, >50% in 3.6% of the tumors. PD-L1 immune cell score >1% was found in 7.1% of the tumors (all of luminal subtype). A weak focal cytoplasmic pan-TRK staining was present in 8.8% but without NTRK fusion. Neither sTILs nor PD-L1 had statistically significant outcomes. Our findings suggest that a subset of MBC patients harbors an immunological environment characterized by increased sTILs with PD-L1 expression. These patients may potentially benefit from immune checkpoint inhibitor therapy. Frequent HER2-low may offer novel anti-HER2 treatment options.

Prognostic relevance of Ki67 expression in primary male breast cancer: determination of cut-off points by different evaluation methods and statistical examinations.

PURPOSE: 1% of all breast cancer cases occur in men. There are significant differences regarding clinical behaviour and genetic profiles between female (FBC) and male breast cancer (MBC). Parameters for decision-making on treatment and prognosis are derived from FBC. Ki67 has a high value as a prognostic and predictive factor in FBC, but accurate Ki67 cut-off points for MBC are missing. In this study, we aimed to evaluate adequate examination methods and reliable cut-off points for Ki67 to assess the highest prognostic value for patient's overall survival (OS). METHODS: In this multicentric retrospective study, histological specimens were obtained from 104 male patients who were diagnosed and treated for primary invasive breast cancer. We applied three methods of Ki67 analysis: Tumor average scoring (TA), tumor border scoring (TB) and hot-spot scoring (HS). Calculated Ki67 cut-off points for each method were assessed as a threshold for patients' overall survival (OS). RESULTS: Ki67 cut-off points were 13.5 for the TA group, 22.5 for the HS group and 17.5 for the TB group. Only Ki67 TA cut-off calculations demonstrated statistical significance (p = 0.04). Ki67 expression analysis of TA showed that more than 90% of patients with low Ki67 levels (< 13.5) were alive after 5-year follow-up. CONCLUSION: Our findings demonstrate that determination of Ki67 expression in TA is the most reliable to define a cut-off point with high prognostic value. A Ki67 cut-off point of 13.5 shows highest statistical power to define luminal A subgroup and OS.

A 64-Year-Old Man With Germline BRCA2-Mutated Breast Cancer: Known and Unknown Aspects of Male Breast Cancer.

Male breast cancer is a rather uncommon and understudied disease. It accounts for less than 1% of all breast cancers, but in recent decades its frequency has been on the rise. Clinical trials of breast cancer have traditionally excluded men. Due to the lack of large-scale prospective studies, most published data come from single-institution, small-cohort studies, and treatment recommendations are based on the extrapolation of data from clinical trials enrolling only women. Although to some extent etiology, diagnosis, and treatment characteristics can be similar, male breast cancer exhibits some distinct features. Men tend to be diagnosed with breast cancer at an older age and at a more advanced stage. A better understanding of the biologic features, clinically relevant differences, effective treatments, and outcomes of male breast cancer is crucial to appropriately manage these patients. We present a male breast cancer case with a germline BRCA2 mutation and discuss the epidemiologic, pathologic, and clinical characteristics along with treatment and follow-up recommendations in view of our recent understanding of this disease.

Deep learning from HE slides predicts the clinical benefit from adjuvant chemotherapy in hormone receptor-positive breast cancer patients.

We hypothesized that a deep-learning algorithm using HE images might be capable of predicting the benefits of adjuvant chemotherapy in cancer patients. HE slides were retrospectively collected from 1343 de-identified breast cancer patients at the Samsung Medical Center and used to develop the Lunit SCOPE algorithm. Lunit SCOPE was trained to predict the recurrence using the 21-gene assay (Oncotype DX) and histological parameters. The risk prediction model predicted the Oncotype DX score > 25 and the recurrence survival of the prognosis validation cohort and TCGA cohorts. The most important predictive variable was the mitotic cells in the cancer epithelium. Of the 363 patients who did not receive adjuvant therapy, 104 predicted high risk had a significantly lower survival rate. The top-300 genes highly correlated with the predicted risk were enriched for cell cycle, nuclear division, and cell division. From the Oncotype DX genes, the predicted risk was positively correlated with proliferation-associated genes and negatively correlated with prognostic genes from the estrogen category. An integrative analysis using Lunit SCOPE predicted the risk of cancer recurrence and the early-stage hormone receptor-positive breast cancer patients who would benefit from adjuvant chemotherapy.

Cytoplasmic DDX3 as prognosticator in male breast cancer.

Male breast cancer (MBC) is a rare disease. Due to its rarity, treatment is still directed by data mainly extrapolated from female breast cancer (FBC) treatment, despite the fact that it has recently become clear that MBC has its own molecular characteristics. DDX3 is a RNA helicase with tumor suppressor and oncogenic potential that was described as a prognosticator in FBC and can be targeted by small molecule inhibitors of DDX3. The aim of this study was to evaluate if DDX3 is a useful prognosticator for MBC patients. Nuclear as well as cytoplasmic DDX3 expression was studied by immunohistochemistry in a Dutch retrospective cohort of 106 MBC patients. Differences in 10-year survival by DDX3 expression were analyzed using log-rank test. The association between clinicopathologic variables, DDX3 expression, and survival was tested in uni- and multivariate Cox-regression analysis. High cytoplasmic DDX3 was associated with high androgen receptor (AR) expression while low nuclear DDX3 was associated with negative lymph node status. Nuclear and cytoplasmic DDX3 were not associated with each other. In a univariate analysis, high cytoplasmic DDX3 (p = 0.045) was significantly associated with better 10-year overall survival. In multivariate analyses, cytoplasmic DDX3 had independent prognostic value (p = 0.017). In conclusion, cytoplasmic DDX3 expression seems to be a useful prognosticator in MBC, as high cytoplasmic DDX3 indicated better 10-year survival.

Brain metastasis with subtype conversion in a patient with male breast cancer: A case report.

RATIONALE: Brain metastasis of male breast cancer is extremely rare, and the pathological changes between the primary tumor and the metastatic brain tumor have not been reported. Herein, we report for the first time a case of male breast cancer with metastasis to the parietal lobe with subtype conversion after metastasis. PATIENT CONCERNS: we describe a 45-year-old male patient admitted for an incidentally found brain tumor after a motorcycle accident. The patient had been treated for breast cancer 5 years previously. The primary tumor was an invasive ductal carcinoma classified as pT1N1M0 with hormone receptor positivity (estrogen receptor ++, progesterone receptor +++, human epidermal growth factor receptor-type2 (HER2) +) and was treated with surgery, adjuvant chemotherapy, radiation therapy and endocrine therapy (tamoxifen). DIAGNOSES: Magnetic resonance imaging revealed a well enhanced focal solid tumor in the right parietal lobe (5.0 × 4.2 cm in size), Immunohistochemical staining revealed cerebral metastases of breast cancer with HER2 subtype conversion (estrogen receptor +++, progesterone receptor +++, HER2 -). INTERVENTIONS: The patient was successfully treated with surgery and whole brain irradiation (3 Gy × 10 fractions). OUTCOMES: There was no additional complication after the surgery and the patient transferred to oncology department for chemotherapy. 2 years later, he had gamma knife radiosurgery due to the recurred brain lesion and after that he discontinued the treatment and opted for hospice care. LESSONS: Male breast cancer with metastasis to the brain is an extremely rare condition. Although a few similar cases have been reported, subtype conversion in similar cases has not been reported. Therefore, we report this case of a male patient with brain metastasis of invasive ductal carcinoma with HER2 status conversion after metastasis.

Prolonged benefit from palbociclib plus letrozole in heavily pretreated advanced male breast cancer: case report.

INTRODUCTION: Breast cancer in men is less common than in women and treatment recommendations are often derived from clinical trials exclusively involving women. Data on efficacy of CDK 4/6 inhibitors, which are the mainstay of treatment for hormone receptor-positive/HER2-negative advanced breast cancer, are lacking in male patients. CASE REPORT: We present a clinical case of prolonged benefit from palbociclib in combination with letrozole and LHRH analogue in a man who had previously been treated with six lines of endocrine therapies and chemotherapy regimens but was still in excellent clinical condition. CONCLUSIONS: This clinical case demonstrates that male breast cancer stands out as an endocrine-sensitive disease, which could potentially benefit from CDK 4/6 inhibitors in combination with endocrine agents even in very heavily pretreated settings of disease, underscoring both the importance of an accurate selection of patients for later treatment lines, taking into account disease history and previous treatment responses, and the peculiarity of breast cancer in men, which deserves dedicated clinical trials to tailor future recommendations.

MALAT-1: LncRNA ruling miR-182/PIG-C/mesothelin triad in triple negative breast cancer.

Breast cancer (BC) remains a major health problem, despite the remarkable advances in cancer research setting. BC is the most common cancer affecting women worldwide. In the context of triple negative breast cancer (TNBC) treatment, major obstacles include late diagnoses and detrimental side effects of chemotherapy and radiotherapy. Research effort was rewarded with the discovery of mesothelin (MSLN), an oncogenic Glycosyl-Phosphatidyl-Inositol (GPI) anchored protein, over-expressed in TNBC. GPI pathway is a post-translational modification that attaches proteins to cellular membrane. MSLN targeted therapy succeeded in early clinical trials, nevertheless, to date, the epigenetic regulation of MSLN and GPI pathway by non-coding RNAs (nc-RNAs) in BC remains an untouched area. Accordingly, our aim is to investigate-for the first time- the impact of simultaneous targeting of MSLN and its associated GPI pathway member, PIG-C, by non-coding-RNAs. Expression profiling of PIG-C, MSLN in BC was performed. Using bioinformatics tools, MALAT-1 and miR-182 were found to target MSLN and PIG-C. MDA-MB-231 cells were transfected with synthetic nc-RNAs. Expression profiling of MSLN, miR-182 and MALAT-1 showed a dramatic over-expression in BC samples. MiR-182 ectopic expression and MALAT-1 silencing increased MSLN and PIG-C transcript levels. However, miR-182 inhibition and miR-182/si-MALAT-1 co-transfection lowered MSLN and PIG-C levels. Finally, si-PIG-C decreased MSLN and PIG-C levels. To conclude, our investigation unravels a new axis in TNBC, where miR-182 can manipulate MSLN and PIG-C. Meanwhile, MALAT-1 is the culprit lncRNA in this novel axis, possibly a sponge for miR-182. Altogether, this sheds light on new targets for BC immune-therapy.

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial.

PURPOSE: NALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens. METHODS: Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL). RESULTS: A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .0004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups. CONCLUSION: N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.

The effect of chemotherapy on survival in patients with nonmetastatic male breast cancer: A population-based observational study.

BACKGROUND: Male breast cancer is a rare malignant disease, accounting for <1% of all breast cancers. The treatment of male breast cancer is mainly extrapolated from the enormous literature and clinical experience in women. The objective of the current study was to assess the relationship between adjuvant chemotherapy and survival in a large population-based cohort of patients with early-stage male breast cancer. METHODS: Men with invasive stage I to stage III breast cancer were identified in the Surveillance, Epidemiology, and End Results cancer database from 1990 to 2014. The effect of chemotherapy on survival was determined using multivariable Cox regression. RESULTS: Of 2713 male patients enrolled, 1817 (66.9%) did not receive chemotherapy. Age, T classification, N classification, tumor grade, and progesterone receptor (PR) status were found to be strong predictors of chemotherapy administration. Chemotherapy was associated with a significant 26% reduction in all-cause mortality (P < .001) and a marginally significant 21% reduction in breast cancer-specific mortality (P = .085). For men with PR-negative breast cancer, use of chemotherapy was associated with improved breast cancer-specific survival (hazards ratio [HR], 0.50; 95% confidence interval [95% CI], 0.28-0.91 [P = .023]) and overall survival (HR, 0.54; 95% CI, 0.37-0.77 [P = .001]). However, chemotherapy did not improve the breast cancer-specific survival for all men with PR-positive tumors (P = .959); it was associated with improved overall survival (HR, 0.78; 95% CI, 0.66-0.92 [P = .004]) for men with PR-positive stage II and stage III breast cancer. CONCLUSIONS: Chemotherapy should be considered for men with PR-negative, nonmetastatic breast cancer and PR-positive, stage II and stage III breast cancer.

Subtyping of male breast cancer by PAM50 and immunohistochemistry: a pilot study of a consecutive Danish cohort.

Male breast cancer (MBC) is a rare disease that is still to be fully understood. In female breast cancer, molecular subtyping by gene expression has proven its significance. In this study, we characterize a consecutive cohort of MBC patients surgically treated from 1997 to 2017, identified at our institution (N = 37), and report the association between molecular subtypes found by a surrogate panel of immunohistochemical (IHC) markers, and the PAM50 signature, as well as risk of recurrence score and overall survival for the different subtypes. PAM50 subtypes were determined using the nCounter FLEX system instrument and software. The distribution of molecular subtypes according to the PAM50 signature was as follows: 56% luminal B, 39% luminal A, and 5% basal-like. None of the tumors were HER2-enriched. Using IHC surrogate markers, we found 80% luminal B-like, 15% luminal A-like, and 5% basal-like. None were HER2-positive (non-luminal). We found a strong statistical association between subtypes found by PAM50 signature and the IHC surrogate markers (p < 0.001). Furthermore, we found luminal A tumors to be smaller in size compared to luminal B tumors (p = 0.04). Patients with luminal A subtype tumors had the lowest ROR scores with a mean of 39, whereas patients with luminal B subtype tumors had a mean ROR score of 69. Significant worse overall survival for luminal B tumors compared to luminal A tumors was seen (p = 0.02). Male breast cancer seems to be a mainly luminal disease, with luminal B being the most frequent subtype. Further studies are needed to ensure correct therapeutic strategies for this select group of patients.

Pharmacological management of male breast cancer.

INTRODUCTION: Despite its rarity, male breast cancer shows a steadily rising incidence. Given the absence of ad hoc prospective randomized clinical trials, treatment strategies are based on extrapolation from female breast cancer recommendations or solely on population-based data. AREAS COVERED: This review discusses the current treatment landscape for male breast cancer in the adjuvant and in the metastatic setting. The authors also discuss the biology and genomic landscape of male breast cancer. Original research and review articles, relative to the period 2010-2019, were included in the review of the literature. EXPERT OPINION: There is a major medical need to include male patients with breast cancer in prospective clinical trials. The call to equality in breast cancer care can be pursued via two divergent paths: (i) a gender-neutral delivery of breast cancer information and (ii) the creation of separate sections, for the more common female breast cancer and for the rare male ones. We propose to differentiate male breast cancer care, acknowledging unique onco-sexual and social needs that can be only partially shared.

Utility of Oncotype DX in Male Breast Cancer Patients and Impact on Chemotherapy Administration: A Comparative Study with Female Patients.

BACKGROUND: Use of the Oncotype DX recurrence score (RS) has been widely adopted in women with early-stage hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER-) breast cancer (BC). Validation studies on the use of RS in male BC (MBC) are lacking. OBJECTIVE: The aim of this study was to identify the utilization of RS and association with chemotherapy recommendations in early-stage MBC compared with female BC (FBC). METHODS: Using the National Cancer Database (NCDB), a retrospective review was performed for patients with T1/T2, node-negative, HR+/HER2- BC between 2010 and 2014. Patients were stratified by demographics, tumor characteristics, RS, and chemotherapy use comparing MBC with FBC over the allotted time period. RESULTS: A total of 358,497 patients-3068 (0.8%) males and 355,429 (99.1%) females-met the inclusion criteria. A smaller proportion of MBC patients received RS testing compared with FBC patients (32% vs. 35%, p < 0.001). Male patients who had RS were younger, had T2 tumors, lymphovascular invasion, and private insurance. The distribution of RS was similar in both groups. Only 4% of MBC patients with low RS received adjuvant chemotherapy, compared with 4.9% of FBC patients. Overall chemotherapy rates were similar in MBC and FBC patients. CONCLUSIONS: Our results showed that RS has not been completely embraced in the management of MBC, although when performed in MBC, chemotherapy recommendations vary based on RS. Whether the use of RS affects the clinical outcomes of MBC is unknown. A prospective registry would help clarify and evaluate the impact of RS on clinical outcomes in MBC.

Androgen receptor expression inversely correlates with histological grade and N stage in ER+/PgRlow male breast cancer.

PURPOSE: Androgen Receptor (AR) positivity is often displayed in breast cancer and especially in Male Breast Cancer (MBC), where it appears to be a heterogeneous feature, with its expression ranging between 38 and 81% of cases. Given the fact that circulating androgens represent the most important sex hormones in males and that breast carcinogenesis is characteristically subjected to hormonal mechanisms, our purpose was to investigate the clinicopathological significance of AR in MBC assessing if its expression could be associated with parameters of tumor aggressiveness. METHODS: Clinical and pathological data were retrospectively reviewed for male patients with a diagnosis of invasive breast cancer. AR status was detected by immunohistochemistry on formalin-fixed, paraffin-embedded tumoral tissue sections. Correlations between AR expression and histopathological features were assessed using univariate and multiple comparisons where appropriate, assuming P values < 0.05 as statistically significant. RESULTS: The study included 44 consecutive male patients. AR expression ranged between 10 and 98% and the majority of cases presented a moderate to high expression of this receptor. Adopting a 20% PgR cut-off, statistical analyses highlighted a different behavior of AR: in ER+/PgRhigh group, it positively correlated with the other steroid receptors pointing out the importance of hormonal cross-talk: in ER+/PgRlow group, AR status inversely correlated with histological grade and lymph node status. CONCLUSION: Hormonal factors reveal to play a crucial role in MBC carcinogenesis and progression. Intriguingly, in ER+/PgRlow tumors AR expression significantly correlates with lymph node status, hinting at a favorable biological role of AR in this tumor subgroup.

Elucidating Determinants of Survival Disparities Among a Real-world Cohort of Metastatic Breast Cancer Patients: A National Cancer Database Analysis.

BACKGROUND: Disparities in breast cancer survival by race/ethnicity and socioeconomic status have been reported. However, it is unclear if these findings are reproducible among subpopulations. This study aimed to assess if socially oriented factors are predictive of overall survival (OS) among patients with hormone receptor-positive (HR+), human epidermal growth factor 2-positive (HER2+) metastatic breast cancer (MBC). PATIENTS AND METHODS: We analyzed patients with MBC included in the National Cancer Database diagnosed with HR+ and HER2+ disease treated between 2010 and 2015. Multivariate analyses describe the association between non-clinical prognostic factors and OS. A matched analysis, which balanced prognostic factors between whites and African Americans (AA), was also conducted. RESULTS: Of the 6200 patients analyzed, the majority were 50 years or older, white, and treated with hormonal therapy. Disparities in OS were observed; multivariate analysis revealed diminished survival was associated with low income (< $38K vs. ≥ $63K, hazard ratio [HR], 1.30; P < .001), having government insurance (government vs. private, HR, 1.55; P < .001), living closer to one's treatment facility (< 4 miles vs. ≥ 18 miles, HR, 1.16; P = .04), and being AA (AA vs. white, HR, 1.20; P = .006). The mortality disparity attributed to race was insignificant in the matched analysis (AA vs. white, HR, 1.13; 95% confidence interval, 0.98-1.30; P = .09). CONCLUSIONS: This study confirms that the known sociodemographic disparities in OS among patients with MBC are similar within the HR+/HER2+ subpopulation. The discordance of outcomes between matched and unmatched analysis demonstrate that there is a highly vulnerable subgroup of AAs. Further investigation is required to determine if the identified associations are independently causal of poor prognosis.

Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer.

BACKGROUND: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of ATM, BRCA1, PALB2, RAD51B, and XRCC3. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables. RESULTS: Only RAD51B and XRCC3 disclosed significant differences between tumor and gynecomastia (p < 0.0001 and p = 0.020, respectively). Assembled in a panel, RAD51B and XRCC3 promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89.5% specificity, and 91.2% accuracy. Moreover, promoter methylation levels were lower in paired non-tumor tissues, comparing to tumor samples. No associations were found between epigenetic alterations and clinicopathological features, as well as with RAD51 and XRCC3 immunoexpression and methylation levels. CONCLUSION: Quantitative promoter methylation of RAD51B and XRCC3 constitutes a promising and accurate biomarker for male BC. Validation in larger series and in liquid biopsies is warranted to confirm its usefulness in detection and monitoring settings.

18F-PSMA 1007 Uptake in a Man With Metastatic Breast Cancer.

A 72-year-old man, who is known with a case of metastatic carcinoma of the breast, was referred for F-PMSA 1007 PET/CT with clinical suspicion of synchronous prostate cancer. F-PSMA 1007 PET/CT scan detected no abnormal tracer concentrating lesion in the prostate gland; however, abnormal tracer concentration was noted in soft tissue lesions in left breast, metastatic lymph nodes, and skeletal lesions. Compared with F-FDG PET/CT, more bone lesions were detected on F-PSMA 1007 imaging. The findings of our case open the possibility of imaging metastatic breast cancer with F-PSMA 1007 in men.

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

BACKGROUND: Breast 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. METHODS: From 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). RESULTS: Of 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). CONCLUSIONS: HGF 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.

Male breast cancer: a closer look at patient and tumor characteristics and factors that affect survival using the National Cancer Database.

OBJECTIVE: To comprehensively describe the tumor and clinical characteristics of breast cancer in a cohort of male patients and to assess the factors that affect survival. BACKGROUND: Much of the standard care of male breast cancer is based on the diagnosis and treatment strategies of female breast cancer. However, important clinical differences between the two have been elucidated, which suggests the need for unique attention to male breast cancer. METHODS: We evaluated the records of male patients who were diagnosed with breast cancer between 2004 and 2015 using the National Cancer Database (NCDB). Data obtained were demographic characteristics, clinical and tumor data, type of therapy, as well as survival data. We used descriptive statistics to characterize our study population. We then performed a survival and Cox proportional hazards analysis. RESULTS: We identified 16,498 patients (median age: 63 years). Several treatment modalities were used, of which surgery was the most common (14,882 [90.4%]). The total follow-up time was 13 years (156 months). Five-year survival was 77.7% (95% CI 76.9-78.4) and 10-year survival was 60.7%. In a Cox proportional hazards model, mastectomy was associated with the greatest survival (hazard ratio [HR] 0.49; p < 0.001). CONCLUSION: We report what is to our knowledge the largest national population-based cohort of male breast cancer patients. Importantly, our data suggests that similar to female patients, several treatment modalities are significantly associated with improved survival in male patients, particularly surgery. Increasing age, black race, government insurance, more comorbidities, and higher tumor stages are associated with decreased survival.

Mammary Paget's Disease of the Male Breast: A Rare Case With an Unusual Immunohistochemical Profile.

Mammary Paget's disease is rare and comprises about 0.62% of all breast cancer cases, only 1.65% of which occur in male patients. This case report involves a 76-year-old man who presented to his primary care physician with an itching, scaly, unilateral lesion involving the nipple skin. He underwent wide local excision of the lesion for a diagnosis of Bowen's disease (squamous cell carcinoma in situ). Histologic examination of the specimen revealed mammary Paget's disease with ductal carcinoma in situ in the underlying breast tissue. A panel of immunohistochemical stains revealed the Paget cells to be positive for cytokeratin 7, MUC1, GATA3, and androgen receptor and negative for cytokeratins 5/6, p63, SOX10, and MART-1/Melan-A. Paget cells were also negative for estrogen receptor and progesterone receptor, and positive for HER2/neu. However, the underlying ductal carcinoma in situ was positive for both estrogen receptor and progesterone receptor and negative for HER2/neu. This discordance, supported by the current literature, suggests an alternative etiology for Paget's disease in certain cases that cannot be explained by the well-established epidermotropic and transformative theories of Paget's disease evolution.