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Male Breast Cancer

Male breast cancer is uncommon, men account for approximately 1% of all breast cancer cases. Incidence in Western populations is under 1 case per 100,000 men, though rates reported in some African countries are much higher. The majority of male breast cancers are of the infiltrating ductal type, this is where the cancer has spread beyond the cells lining ducts in the breast. In many respects male breast cancer is similar to that found in women, though in general men tend to be older than women at diagnosis. Treatment tends to be the same as that for women with breast cancer of the same type and stage.

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  • PubMed search for publications about Male Breast Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Male Breast Cancer
    MeSH term: Breast Neoplasms, Male
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Ballatore Z, Pistelli M, Battelli N, et al.
Everolimus and exemestane in long survival hormone receptor positive male breast cancer: case report.
BMC Res Notes. 2016; 9(1):497 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Male breast cancer is a rare event, accounting for approximately 1% of all breast carcinomas. Although men with breast cancer had poorer survival when compared with women, data on prognosis principally derive from retrospective studies and from extrapolation of female breast cancer series. We reported the case of a very long survival patient.
CASE PRESENTATION: A caucasian 42-year-old man underwent radical mastectomy with axillary dissection for breast cancer in 1993. Pathologic stage was pT4pN0M0 infiltrating ductal carcinoma of right breast without lymph nodes metastases. Biological characterization was not available. He received adjuvant treatment with chemotherapy, six cycles of cyclophosphamide, methotrexate and fluorouracil, then endocrine therapy with tamoxifen for 5 years and complementary radiotherapy. Then he began clinical-instrumental follow up. In May 1996, a computed tomography scan showed multiple lung metastases. Hereafter he received several oncologic treatment including seven chemotherapy and five endocrine therapy lines with two re-challenge of endocrine therapy. In October 2007 further lung progression was showed and a biopsy was performed to characterize the disease. Histological examination confirmed breast cancer metastases, immunohistochemistry showed positive staining for estrogen receptor, negative for progesterone receptor and human epithelial growth factor receptor 2, proliferative index was 21%. In April 2013, bone disease progression was evident and he received radiant treatment to sacral spine. In May 2014 an off-label treatment with exemestane and everolimus combination was approved by Ethics Committee of the Marche Region. The patient received treatment for 3 months with evident clinical benefit to subcutaneous lesions of the chest wall that were not visible nor palpable on physical examination after 1 month of treatment.
CONCLUSION: That is the case of long survival male breast cancer patient with luminal B subtype and no BRCA mutations. He achieved higher progression free survival with endocrine therapy creating the rationale for last line treatment with everolimus and exemestane combination. Attending conclusive results from ongoing studies, everolimus and exemestane should not be used routinely in male metastatic breast cancer patients, but taking into account for selected cases. At the best of our knowledge, this is the first case of male beast cancer treated with exemestane and everolimus combination.

Lin FI, Gonzalez EM, Kummar S, et al.
Utility of (18)F-fluoroestradiol ((18)F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy.
Eur J Nucl Med Mol Imaging. 2017; 44(3):500-508 [PubMed] Related Publications
BACKGROUND: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. (18)F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes (18)F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen.
METHODS: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with (18)F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with (18)F-FES 1-5 days post administration of Z-endoxifen.
RESULTS: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration.
CONCLUSION: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

Kuba S, Ishida M, Oikawa M, et al.
Aromatase inhibitors with or without luteinizing hormone-releasing hormone agonist for metastatic male breast cancer: report of four cases and review of the literature.
Breast Cancer. 2016; 23(6):945-949 [PubMed] Related Publications
The roles of aromatase inhibitors (AIs) and luteinizing hormone-releasing hormone (LH-RH) agonists in the management of male breast cancer remain uncertain, with no reports in Japanese men. We report four Japanese male patients with metastatic breast cancer treated with AIs with or without an LH-RH agonist, and consider the relationship between treatment effect and estradiol (E2) concentration. Three patients were initially treated with AI alone after selective estrogen receptor modulators (SERMs), and one received AIs plus an LH-RH agonist after a SERM. Two patients treated with an AI alone responded, one patient with E2 levels below the lower assay limit and the other with levels above the limit. The other treated with an AI alone experienced progression regardless of the E2 levels below the lower assay limit, however, responded after the addition of an LH-RH agonist. E2 concentrations were related to the efficacy of treatment in one patient. The patient initially treated with an AI plus an LH-RH agonist also responded. No grade 3 or 4 adverse events were observed in any of the patients treated with AIs with or without an LH-RH agonist. AIs with or without an LH-RH agonist offer an effective treatment option for hormone receptor-positive metastatic male breast cancer.

Katayama Y, Motoki T, Watanabe S, et al.
A very rare case of breast cancer in a female-to-male transsexual.
Breast Cancer. 2016; 23(6):939-944 [PubMed] Related Publications
The incidence of breast cancer in female-to-male (FTM) transsexuals who received mastectomy and sex reassignment surgery is very rare. In fact, there is only one previous medical report of such a case. We experienced a case of an FTM transsexual who developed breast cancer 12 years after mastectomy and hysterectomy with bilateral salpingo-oophorectomy. Because he had been continuously receiving testosterone during the last 15 years and because histopathological examination revealed positive estrogen receptor and androgen receptor expression, we suggest that exogenous testosterone may have initiated the development of breast cancer via two distinct pathways. We describe the clinical course and condition of the patient and recommend that medical personnel consider the possibility of hormone-related cancer in FTM transsexuals receiving cross-sex hormones.

Hugentobler A, Gilbeau L, Talbot JN, Gauthé M
18F-Fluorocholine PET/CT of Incidental Male Breast Cancer.
Clin Nucl Med. 2017; 42(1):e56-e57 [PubMed] Related Publications
Breast cancer is approximately 100 times less common among men. Estrogen-related receptor α was detected in human prostate cancer tissue, and androgen receptors are expressed in both normal and malignant breast tissue. Thus, prostate cancer hormonal therapy may increase breast cancer risk. A 67-year-old man with prostate cancer history presented with rising prostate-specific antigen level. F-Fluorocholine PET/CT showed intense uptake in his right breast and moderate uptake in right axillary lymph node. Complementary F-FDG PET/CT demonstrated more intense tracer uptakes in both the right breast and axillary lymph node. Breast histological findings were invasive ductal cancer, with axillary lymph node invasion.

Vadrucci M, Gilardi L, Grana CM
Breast Cancer Incidentally Detected by 18F-Choline PET/CT in a Patient With Recurrent Prostate Carcinoma.
Clin Nucl Med. 2016; 41(11):892-893 [PubMed] Related Publications
A 79-year-old man underwent F-choline PET/CT for biochemical recurrence of prostate cancer. PET/CT images showed an area of elevated radiopharmaceutical uptake in a left pelvic node. In addition, a small focus of increased radiolabeled choline accumulation was seen in a small nodule of the right breast, which was later histologically characterized as an infiltrating ductal carcinoma. In this patient, choline PET/CT was critical in localizing prostate cancer recurrence and identifying a second unsuspected malignancy.

Plasilova ML, Hayse B, Killelea BK, et al.
Features of triple-negative breast cancer: Analysis of 38,813 cases from the national cancer database.
Medicine (Baltimore). 2016; 95(35):e4614 [PubMed] Free Access to Full Article Related Publications
The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC was present in 38,628 of 295,801 (13%) female patients compared to 185 of 3136 (6%) male patients (P < 0.001). The incidence of TNBC varied by region from 10.8% in New England to 15.8% in the east south central US (P < 0.001), as well as by race with the highest rates in African-Americans (23.7%), and lowest in Filipino patients (8.9%). The incidence of TNBC also varied by histology, accounting for 76% of metaplastic cancers, but only 2% of infiltrating lobular carcinomas. TNBCs were significantly larger than non-TNBC (mean 2.8 cm vs 2.1 cm, P < 0.001), and more TNBC were poorly differentiated compared to other subtypes (79.7% vs 25.8%, P < 0.001). On univariate analysis, TNBC was no more likely than non-TNBC to have node-positive disease (32.0% vs 31.7%, respectively, P = 0.218) but in a multivariable analysis controlling for tumor size and grade, TNBC was associated with significantly less node-positivity (OR = 0.59; 95% confidence interval [CI]: 0.57-0.60). TNBC has distinct features regarding age, gender, geographic, and racial distribution. Compared to non-TNBC, TNBC is larger and higher grade, but less likely to have lymph node metastases.

Karihtala P, Rissanen T, Tuominen H
Male Malignant Phyllodes Breast Tumor After Prophylactic Breast Radiotherapy and Bicalutamide Treatment: A Case Report.
Anticancer Res. 2016; 36(7):3433-6 [PubMed] Related Publications
Phyllodes tumor in male breast is an exceptionally rare neoplasm with only few published case reports. Herein, we present a case of malignant phyllodes tumor in male breast nine years after prophylactic breast 10 Gy radiotherapy and after nine year bicalutamide treatment. The imaging findings of the tumor and pathological correlation are also presented.

Amirifard N, Sadeghi E
Breast Cancer in Men: a Report from the Department of Radiation Oncology in Kermanshah Province, Iran.
Asian Pac J Cancer Prev. 2016; 17(5):2593-6 [PubMed] Related Publications
BACKGROUND: Male breast cancer (MBC) is a rare disease that accounts for less than 1% of all cancers in men and less than 1% of all diagnosed breast cancers. In this study, we retrospectively evaluated the clinicopathological features, treatment options and overall survival in Kurdish MBC cases.
MATERIALS AND METHODS: Seventeen MBC were referred to Department of Radiation Oncology in Imam Reza Hospital, Kermanshah, Iran, between 2010 and 2016. Immunohistochemical analysis was performed for ER, PR and Her2 biomarkers and FISH for those with Her2 2+. Median follow-up period was 30 months (2-65 months). We excluded from the study patients who did not have follow-up after initial diagnosis. Treatment methods were chemotherapy, radiotherapy, hormonal therapy, target therapy and palliative care. Survival was estimated by the Kaplan Meier method (Prism 5).
RESULTS: The mean age at diagnosis was 49.2 ± 17 years (range, 24-85 years). Grade II was the most grade in MBC (65%). Fourteen patients (82%) had invasive ductal carcinoma, one (6%) had ductal carcinoma in situ and 2 (12%) had invasive papillary. ER, PR and Her2 were significantly positive in 14/17, 8/17 and 2/17 cases, respectively. The treatment included modified radical mastectomy for most patients. Chemotherapy with TAC and CEF regimens was delivered to 15/17 cases. Tamoxifen therapy was delivered to 14/17 cases. Three stage IV patients received Avestin and two with Her2 3+ were given Trastuzumab (Herceptin). Patients received adjuvant radiotherapy following surgery and chemotherapy. The site of metastasis was the bone in 2 cases, lung in 1 case and liver in 1 case. Zoledronic acid (Zometa) was prescribed for patients with bone metastasis. Five-year overall survival rate was 64%.
CONCLUSIONS: MBC is rare. Thus, we need larger studies are in collaboration with several research centers in the field of breast cancer. ER positive, grade II of invasive ductal carcinoma, stage II and right side happened more with MBC. Overall survival is similar to other studies.

Melo Abreu E, Pereira P, Marques JC, Esteves G
Invasive lobular carcinoma: a rare presentation in the male breast.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Breast cancer in men is uncommon, accounting for <1% of all breast cancers. Even though lobular structures are quite infrequent in the male breast, rare cases of invasive lobular breast carcinoma have been described, representing 1-2% of all breast cancers in men. Risk factors include undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury, infertility and Klinefelter's syndrome, previous thoracic radiotherapy, alterations of the oestrogen-testosterone ratio and familial history (BRCA 2 and 1). The authors present a case of a 52-year-old man with no relevant predisposing factors to breast cancer, who presented with a painless, firm nodule, fixed to the nipple on the left breast, associated with nipple retraction and ulceration, and fully characterised by mammogram and ultrasound. Histopathological and immunohistochemical analysis revealed the diagnosis of invasive lobular breast carcinoma and the patient underwent left radical mastectomy, followed by adjuvant chemotherapy, radiotherapy and hormonotherapy. A brief review of the literature is presented.

Patel F, Achuthan R, Hyklova L, et al.
Management of breast cancer in an Asian man with post-traumatic stress disorder: a case report.
J Med Case Rep. 2016; 10(1):77 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Migration to the UK has increased considerably, which is reflected in the diverse multicultural population which includes asylum seekers and economic migrants. Differences in ethnic and cultural values between the host and newcomer populations could impact on effective health care provision, especially in gender-biased conditions such as breast cancer. Breast cancer is rare in men and the diagnosis is often met with disbelief. This case report describes an unusual case of breast cancer in an Afghan man who is an asylum seeker of Asian ethnic origin.
CASE PRESENTATION: A focused ethnographic case study and in-depth interview was used to gain qualitative data and insight into the personal experiences of a male Afghan asylum seeker, age unknown (estimated to be in his 30s), with post-traumatic stress disorder who was electively admitted into hospital for the investigation of a suspicious lump in his left breast, which was subsequently found to be breast cancer. He was extremely reluctant to accept a breast cancer diagnosis and initially would not consent to any treatment, preferring to seek further opinion. During consultation with various members of the breast team he continually declined to accept the diagnosis and felt there was an error in the investigative protocol. Through the involvement of a Muslim nurse, fluent in Urdu and knowledgeable of the Afghan culture and religious background, we learned about his experiences and feelings; he opened up to her about his experiences in Afghanistan, detailing his experiences of trauma as a result of war, and disclosing that he had been diagnosed as having post-traumatic stress disorder by his physician. He saw breast cancer as a "woman's disease" which deeply affected his feelings of masculinity and left him feeling vulnerable.
CONCLUSIONS: While sensitivity is undoubtedly required when diagnosing gender-biased conditions such as breast cancer in men, our experience showed this is exacerbated in ethnic minority groups where language barriers often exist and awareness of cultural differences is required. Awareness of the possibility of post-traumatic stress disorder in migrant populations from conflict-torn areas is also recommended during consultation.

Zografos E, Gazouli M, Tsangaris G, Marinos E
The Significance of Proteomic Biomarkers in Male Breast Cancer.
Cancer Genomics Proteomics. 2016 May-Jun; 13(3):183-90 [PubMed] Related Publications
Breast cancer in men (MBC) is an uncommon malignancy and accounts for only 1% of all diagnosed breast cancers. By using genomic and transcriptomic approaches, researchers have been able to expand our insight into the genetic basis of breast cancer, by providing new biomarkers. We currently know that gene analysis by itself does not show the complete picture. Along with the genomic approach, proteomics are crucial for the improvement of breast cancer diagnosis, sub-classification, for predicting response to different treatment modalities and for predicting prognosis. There are great challenges in identifying discriminatory proteins and the use of specific techniques along with additional analytical tools is required. A number of techniques allow testing for proteins produced during specific diseases. In this review, an effort is made to summarize the studies and results linked to the implementation of proteomics in the field of MBC detection and diagnosis.

Choi MY, Lee SK, Lee JE, et al.
Characterization of Korean Male Breast Cancer Using an Online Nationwide Breast-Cancer Database: Matched-Pair Analysis of Patients With Female Breast Cancer.
Medicine (Baltimore). 2016; 95(16):e3299 [PubMed] Free Access to Full Article Related Publications
The aim of this study is to review the characteristics and the survival rate in male breast cancer (MBC) patients in Korea over a 31-year period. Additionally, we analyzed the overall survival (OS) rate of a group of MBC matched to females with breast cancer. We retrospectively analyzed the data from 400 Korean patients who were treated for MBC from 1978 to 2009. Patient demographics and clinical information were routinely documented throughout the study period. Survival and prognostic factors were evaluated. Each MBC patient was matched with 5 female breast cancer (FBC) patients based on 7 characteristics and we compared the OS rates between the 2 groups. For MBC cases, the median follow-up was 72 months and the 5-year OS rate was 85.9%. In univariate analyses, the prognostic factors influencing OS were age (more than 60 years, P <0.001), tumor size (>2 cm, P = 0.007), and having a negative progesterone receptor (PR) status (P = 0.042). Only the age (P = 0.028) and tumor size (P = 0.024) were significant prognostic factors for OS in multivariate analysis. After matching, we had 260 male patients matched to 1300 female patients for analysis. Compared with cases among females, the rate of mastectomy was higher among MBC cases and tumors, which were almost invasive ductal carcinomas (IDCs), were more likely to be located in the central part of the breast. For MBC cases, the percentage of adjuvant radiation therapy was low compared with female cases. The primary hormone therapy agent used was tamoxifen. The 5-year OS rates were similar in MBC compared with FBC (91.0% vs. 92.6%, P = 0.300). We found that only the age (more than 60 years) and tumor size were independent prognostic factors of survival in MBC. The prognosis for MBC is similar to that for FBC given similar stage and hormone-receptor status.

Alazhri J, Saclarides C, Avisar E
A rare complication resulting in a rare disease: radiation-induced male breast cancer.
BMJ Case Rep. 2016; 2016:10.1136/bcr-2015-211874 [PubMed] Related Publications
The increase in survival after childhood radiation therapy for some blood malignancies has led to an increase in the diagnosis of radiation-induced secondary solid malignancies (SSM). We report a young man presenting with invasive breast cancer 19 years after receiving radiation therapy and bone marrow transplant for acute lymphocytic leukaemia in childhood. This latency period is longer than previously reported. Therefore, survivors of radiation-treated primary cancer should be closely monitored for SSM, including breast cancer, for the rest of their lives.

Leone JP, Zwenger AO, Iturbe J, et al.
Prognostic factors in male breast cancer: a population-based study.
Breast Cancer Res Treat. 2016; 156(3):539-48 [PubMed] Related Publications
Prognostic factors in male breast cancer (MaBC) are controversial. The objective of this study was to analyze patient characteristics and prognostic factors in MaBC over the last decade. Using the Surveillance, Epidemiology, and End Results program, we extracted MaBC patients diagnosed between 2003 and 2012. Patient characteristics were compared between tumor grades. We conducted univariate and multivariate analyses to determine the effects of each prognostic variable on overall survival (OS). The study included 2992 patients. The majority had ductal (85 %), ER-positive (95.1 %), and PR-positive (86 %) breast cancer; however, only 12.4 % had grade I tumors. Stage I and II disease represented 73 % of cases. There was a significant association between grade III/IV tumors with ductal histology, ER and PR negativity, advanced stage, receipt of mastectomy and radiotherapy, and breast cancer death (all P < 0.05). ER-positive patients had better OS (hazard ratio 0.69, P = 0.03); however, after 7.5 years, OS rates by ER status were similar. In multivariate analysis, older age, grade III/IV tumors, stage IV disease, no surgery, no radiotherapy, ER-negative tumors, and unmarried patients had significantly shorter OS (all P < 0.05). Over the past decade, MaBC has been diagnosed most frequently with early stages of disease and high rates of ER positivity; however, grade I is uncommon. ER positivity is associated with better prognosis, mainly during the first 5 years after diagnosis. Age at diagnosis, tumor grade, stage, surgery, radiotherapy, ER, and marital status have clear impact on OS in MaBC.

Abreu MH, Afonso N, Abreu PH, et al.
Male breast cancer: Looking for better prognostic subgroups.
Breast. 2016; 26:18-24 [PubMed] Related Publications
PURPOSE: Male Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted.
PATIENTS/METHODS: Retrospectively revision of 111 cases treated in the same Cancer Center. Blinded-central pathological revision with immunohistochemical (IHQ) analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female Breast Cancer (FBC) subgroups (based in ER, PR, HER2, 2000 classification, and in ER, PR, HER2, ki67, 2013 classification) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel.
RESULTS: According to FBC classifications, the majority of tumors were luminal: A (89.2%; 60.0%) and B (7.2%; 35.8%). Triple negative phenotype was infrequent (2.7%; 3.2%) and HER2 enriched, non-luminal, was rare (≤1% in both). In multivariate analysis the poor prognostic factors were: size >2 cm (HR:1.8; 95%CI:1.0-3.4 years, p = 0.049), absence of ER (HR:4.9; 95%CI:1.7-14.3 years, p = 0.004) and presence of distant metastasis (HR:5.3; 95%CI:2.2-3.1 years, p < 0.001). FBC subtypes were independent prognostic factors (p = 0.009, p = 0.046), but when analyzed only luminal groups, prognosis did not differ regardless the classification used (p > 0.20). Clustering defined different subgroups, that have prognostic value in multivariate analysis (p = 0.005), with better survival in ER/PR+, AR-, HER2-and ki67/p53 low group (median: 11.5 years; 95%CI: 6.2-16.8 years) and worst in PR-group (median:4.5 years; 95%CI: 1.6-7.8 years).
CONCLUSION: FBC subtypes do not give the same prognostic information in MBC even in luminal groups. Two subgroups with distinct prognosis were identified in a common six-IHQ panel. Future studies must achieve their real prognostic value in these patients.

Sas-Korczynska B, Adamczyk A, Niemiec J, et al.
Androgen receptor in male breast cancer.
Pol J Pathol. 2015; 66(4):347-52 [PubMed] Related Publications
We present the androgen receptor (AR) status in 32 breast cancers diagnosed in male patients. Androgen receptor expression was found in 62.5% tumors and it was more frequent (85% of cases) in estrogen-positive tumours. The analyses of its impact on treatment results showed that AR immmunopositivity is a prognostic factor for overall survival, and AR immunonegativity is also correlated with worse prognosis (distant metastases developed more frequently and earlier).

Fentiman IS
Male breast cancer is not congruent with the female disease.
Crit Rev Oncol Hematol. 2016; 101:119-24 [PubMed] Related Publications
It has become customary to extrapolate from the results of treatment trials for female breastcancer and apply them to males with the disease. In the absence of results from national and international randomised trials for male breast cancer (MBC) this appears superficially to be an appropriate response. Closer examination of available data reveals that aspects of the aetiology and treatment of MBC do not fit the simplistic model that men usually have endocrine sensitive tumours which behave like those in postmenopausal women. Most females and males with breast cancer have none of the recognised risk factors, indicating the gaps in our knowledge of the epidemiology of this disease. Several studies have compared epidemiological risk factors for MBC and female breast cancer (FBC) but many have been blighted by small numbers. In comparison with FBC there is a larger proportion of BRCA2 tumours, (occurring in 10% of MBC), and underrepresentation of BRCA1 tumours (found in only 1%), suggesting significant differences in the genetic aetiology of MBC and FBC. Genome-wide association studies in FBC reported single nucleotide polymorphisms (SNPs) in 12 novel independent loci were consistently associated with disease but for MBC 2 SNPs had a significantly increased risk. Molecular profiles of matched cancers in males and females showed a gender-associated modulation of major processes including energy metabolism, regulation of translation, matrix remodelling and immune recruitment. Immunohistochemistry for kinase inhibitor proteins (KIPs) p27Kip1 and p21Waf1 indicate a significant difference in the immunostaining of tumours from male patients compared with females. MBC is almost always estrogen receptor positive (ER+ve) and so systemic treatment is usually endocrine. With evidence in FBC that aromatase inhibitors are more effective than tamoxifen in the postmenopausal it was seemingly logical that the same would be true for MBC. Results however suggest less efficacy with AIs and an increase in risk of mortality compared to tamoxifen. The overall survival in male breast cancer was significantly better after adjuvant treatment with tamoxifen compared to an aromatase inhibitor. These important biological differences point the way to the development of new therapies for MBC based on differences rather than similarities with FBC.

Franceschini G, Sanchez AM, Di Leone A, et al.
Penile cancer metastasizing to the breast: a case report.
J Med Case Rep. 2016; 10:53 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Penile cancer is a relatively uncommon cancer in developed nations. Metastatic disease is rare, but lymphatic or vascular spreading has been previously reported to the liver, lungs, bones, brain, heart and skin.
CASE PRESENTATION: We report a case of a 49-year-old white man with a penile squamous cell carcinoma previously treated with partial penectomy and bilateral inguinal lymph node dissection, followed by adjuvant therapy. Three years after treatment, the primitive neoplasm metastasized to the breast, presenting as a painful lump. Differentials of a secondary versus a malignant primary tumor were considered and in view of a diagnostic dilemma the lesion was excised.
CONCLUSIONS: This case is unusual in its site of metastatic progression as well as in its pattern of clinical presentation. Awareness of such a condition by physicians is mandatory in order to make an early diagnosis and start prompt and correct therapeutic planning.

Gogia A, Raina V, Deo SV, et al.
Male breast cancer: A single institute experience.
Indian J Cancer. 2015 Oct-Dec; 52(4):526-9 [PubMed] Related Publications
BACKGROUND: Male breast cancer (MBC) is a rare disease and accounts for 1% of all breast cancers. There is limited data on MBC from India. The aim of our study was to assess clinico-pathological parameters and outcome in MBC patients.
MATERIALS AND METHODS: This analysis was carried out in 76 patients of MBC who were registered at Institute Rotary Cancer Hospital of All India Institute Of Medical Sciences between 1996 and 2012. Patients' records were retrospective reviewed and data obtained from the computer database using International Classification of Diseases code (C-50).
RESULTS: The median age was 59 years (range: 28-80). The median duration of symptoms was 11 months (range: 0.5-40). Breast lump was the most common presenting symptom (left > right side). American Joint Committee on Cancer (7th edition) stage distribution was Stage I-2.6%, Stage II-13.1%, Stage III-59.3% and Stage IV-25%. Modified radical mastectomy was the commonest surgical procedure. Moreover, 30% of tumors were high-grade and 70% had pathological node positive disease. Estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2)/neu positivity was 80% and 28%, respectively. Triple negative breast cancer constituted 19% of cases. With a median follow-up of 36 months, 3 years relapse free survival and overall survival was 60% and 80%. Advanced stage and visceral metastasis at baseline predicted poor outcome.
CONCLUSION: MBC constituted 0.8% at our institute. Our study population had a longer time to presentation, advanced disease at presentation, more HER2/neu positivity and triple negativity higher than the available literature.

Silvestri V, Barrowdale D, Mulligan AM, et al.
Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.
Breast Cancer Res. 2016; 18(1):15 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).
METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.
RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)).
CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Yoshizawa K, Yuki M, Kinoshita Y, et al.
Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure--Potential for human male breast cancer model.
Exp Toxicol Pathol. 2016; 68(5):263-70 [PubMed] Related Publications
The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans.

Grundy A, Harris SA, Demers PA, et al.
Occupational exposure to magnetic fields and breast cancer among Canadian men.
Cancer Med. 2016; 5(3):586-96 [PubMed] Free Access to Full Article Related Publications
Occupational magnetic field (MF) exposure has been suggested as a risk factor for breast cancer in both men and women. Due to the rarity of this disease in men, most epidemiologic studies investigating this relationship have been limited by small sample sizes. Herein, associations of several measures of occupational MF exposure with breast cancer in men were investigated using data from the population-based case-control component of the Canadian National Enhanced Cancer Surveillance System. Lifetime job histories were provided by 115 cases and 570 controls. Average MF exposure of individual jobs was classified into three categories (<0.3, 0.3 to <0.6, or ≥0.6 μT) through expert blinded review of participant's lifetime occupational histories. The impact of highest average and cumulative MF exposure, as well as exposure duration and specific exposure-time windows, on cancer risk was examined using logistic regression. The proportion of cases (25%) with a highest average exposure of ≥0.3 μT was higher than among controls (22%). We found an elevated risk of breast cancer in men who were exposed to ≥0.6 μT (odds ratio [OR] = 1.80, 95% CI = 0.82-3.95) when compared to those with exposures <0.3 μT. Those exposed to occupational MF fields for at least 30 years had a nearly threefold increase in risk of breast cancer (OR = 2.77, 95% CI = 0.98-7.82) when compared to those with background levels of exposure. Findings for the other time-related MF variables were inconsistent. Our analysis, in one of the largest case-control studies of breast cancer in men conducted to date, provides limited support for the hypothesis that exposure to MF increases the risk breast cancer in men.

Brown GR
Breast Cancer in Transgender Veterans: A Ten-Case Series.
LGBT Health. 2015; 2(1):77-80 [PubMed] Related Publications
All known cases of breast cancer in patients with a diagnosis consistent with transgender identification were identified in the Veterans Health Administration (1996-2013). Ten cases were confirmed: seven birth sex females and three birth sex males. Of the three birth sex males, two identified as gender dysphoric male-to-female and one identified as transgender with transvestic fetishism. The birth sex males all presented with late-stage disease that proved fatal, whereas most of the birth sex female transgender veterans presented with earlier stage disease that could be treated. These cases support the importance of screening for breast cancer using standard guidelines in birth sex males and females. Family history of breast cancer should be obtained from transgender people as part of routine care. This report expands the known cases of breast cancer in transgender persons from 5 to 12 (female-to-male) and from 10 to 13 (male-to-female).

Deb S, Lakhani SR, Ottini L, Fox SB
The cancer genetics and pathology of male breast cancer.
Histopathology. 2016; 68(1):110-8 [PubMed] Related Publications
Male breast cancer (MBC) is an uncommon and poorly understood disease. Recent molecular studies have shown important differences from female breast cancer which are likely to influence treatment strategies from the current female-based management towards a more tailored approach. Significantly more MBCs than female breast cancers arise with an underlying germline cancer predisposition, and display a vastly different penetrance compared with females. Furthermore, the genophenotypical association of basal-like cancer with BRCA1 present in female breast cancer is not observed in male breast cancer. Differences in somatic changes between male and female breast cancer have also been reported, with particular enrichment of PIK3CA mutations and a paucity of TP53 mutations. In general, chromosomal-based changes, in particular regions of gains, are seen more frequently in male than female breast cancer and methylation is seen less frequently. Clinically, several molecular subtypes with prognostic relevance have been described, including chromosomal complex high and methylation high groups, and subgroups with profiling signatures pertaining to epithelial mesenchymal transition and hormonal therapy insensitivity. As with female breast cancer, attention to male specific multicentre trials based on the individual characteristics are needed, together with establishment of reliable preclinical models to understand more clearly the pathogenesis of male breast cancer and improve the general poor outcome of this disease.

Zaenger D, Rabatic BM, Dasher B, Mourad WF
Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?
Clin Breast Cancer. 2016; 16(2):101-4 [PubMed] Related Publications
INTRODUCTION: Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate.
MATERIALS AND METHODS: We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS).
RESULTS: We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2.
CONCLUSION: The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions.

Wong HY, Wang GM, Croessmann S, et al.
TMSB4Y is a candidate tumor suppressor on the Y chromosome and is deleted in male breast cancer.
Oncotarget. 2015; 6(42):44927-40 [PubMed] Free Access to Full Article Related Publications
Male breast cancer comprises less than 1% of breast cancer diagnoses. Although estrogen exposure has been causally linked to the development of female breast cancers, the etiology of male breast cancer is unclear. Here, we show via fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two independent cohorts of male breast cancer patients. We also show somatic loss of the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of loss at this locus in male breast cancers. To further understand the function of TMSB4Y, we created inducible cell lines of TMSB4Y in the female human breast epithelial cell line MCF-10A. Expression of TMSB4Y resulted in aberrant cellular morphology and reduced cell proliferation, with a corresponding reduction in the fraction of metaphase cells. We further show that TMSB4Y interacts directly with β-actin, the main component of the actin cytoskeleton and a cell cycle modulator. Taken together, our results suggest that clonal loss of the Y chromosome may contribute to male breast carcinogenesis, and that the TMSB4Y gene has tumor suppressor properties.

Ferzoco RM, Ruddy KJ
The Epidemiology of Male Breast Cancer.
Curr Oncol Rep. 2016; 18(1):1 [PubMed] Related Publications
Male breast cancer is a rare disease, accounting for only 1% of breast cancer diagnoses in the USA. The current literature suggests that genetic factors including BRCA2 mutations, family history, age, androgen/estrogen imbalance, and environmental exposures may predispose to male breast cancer. In this manuscript, we will review known and possible risk factors for male breast cancer, as well as describe the clinical patterns of the disease.

Quincey K, Williamson I, Winstanley S
'Marginalised malignancies': A qualitative synthesis of men's accounts of living with breast cancer.
Soc Sci Med. 2016; 149:17-25 [PubMed] Related Publications
RATIONALE: Breast cancer in men is a rare, under-researched illness frequently overlooked within both clinical and third-sector healthcare systems. Increased prevalence and high profile awareness-raising, advocacy and activism around breast cancer in women has led to pervasive feminisation of the disease, prompting a misperception of breast cancer as a women-only illness. This deters men from seeking medical attention, professional and social support, and increases sensitivity to body image concerns.
METHODS: Drawing on the principles of critical health psychology, we offer an interpretive and evaluative qualitative synthesis of existing academic literature in the field, and reveal how the marginalisation of men with breast cancer poses a host of psychosocial and psychosexual difficulties for patient-survivors beyond the primary cancer challenge at all stages of the illness trajectory.
RESULTS: We discuss how identities, masculinities, coping responses and resources, and relationships are often affected, and demonstrate how current approaches to breast cancer serve to isolate men who develop the illness, potentially alienating and emasculating them.
CONCLUSION: Our analysis integrates and enhances the findings of the original papers through more theorised considerations of stigma, masculinity and marginalisation. Further, we briefly consider some of the ways men's experiences diverge and converge with women's accounts, and discuss the importance of re-appraising 'pink ribbon culture' for both men and women. We conclude with some recommendations for advocacy and intervention in professional and lay contexts.

Zhu J, Davis CT, Silberman S, et al.
A role for the androgen receptor in the treatment of male breast cancer.
Crit Rev Oncol Hematol. 2016; 98:358-63 [PubMed] Related Publications
Male breast cancer (BC) is relatively rare, making up less than 1% of all breast cancer cases in the United States. Treatment guidelines for male BC are derived from studies on the treatment of female BC, and are based molecular and clinical characteristics, such as hormone receptor positivity. For female estrogen receptor positive (ER+) breast cancers, the standard of care includes three classes of endocrine therapies: selective estrogen receptor modulators, aromatase inhibitors, and pure anti-estrogens. In contrast to female ER+ breast cancers, there is less known about the optimal treatment for male ER+ BC. Furthermore, in contrast to ER, less is known about the role of the androgen receptor (AR) in male and female BC. We report here the treatment of a 28-year-old man with metastatic AR+, ER+ breast cancer otherwise refractory to chemotherapy, who has had a durable clinical response to hormonal suppression with the combination of aromatase inhibition (Letrozole) in conjunction with a GnRH agonist (Leuprolide).

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