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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]

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    MeSH term: Breast Neoplasms, Male
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Latest Research Publications

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

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).

Loewen AH, Schilling SD, Milroy M, Villanueva ML
Case Report: Hormone Receptor Positive, HER2/neu Negative Inflammatory Breast Cancer in a Male Patient.
S D Med. 2015; 68(10):435-7, 439-40 [PubMed] Related Publications
Inflammatory breast cancer is a rare and aggressive disease found almost exclusively in women. We present a case of a 51-year-old male with inflammatory breast carcinoma. The patient presented with a mass measuring roughly 7 cm with overlying erythema, peau d'orange appearance, and prominent nipple retraction. Core biopsy analysis demonstrated estrogen and progesterone receptor positive, HER2/neu receptor negative invasive ductal carcinoma. A PET scan revealed contralateral supraclavicular lymph node metastasis. The patient refused chemotherapy and radiation and was not a surgical candidate. Ultimately he opted for therapy with strictly an aromatase inhibitor. Most recent follow-up at 12 months demonstrated improvement of metastatic lesions on PET scan. Local progression of disease was noted on physical exam and the patient decided to add everolimus and radiation therapy while continuing an aromatase inhibitor. Retrospective studies have demonstrated increased survival of inflammatory breast cancer diagnosed in women with the utilization of neoadjuvant chemotherapy, surgical excision, and radiation therapy. Unfortunately, due to the rarity of the disease, no specific optimal treatment guidelines have been established for men diagnosed with this disease.

Di Oto E, Monti V, Cucchi MC, et al.
X chromosome gain in male breast cancer.
Hum Pathol. 2015; 46(12):1908-12 [PubMed] Related Publications
Male breast cancer (MBC) is an uncommon disease whose molecular profile is not well known. X chromosome gain has been described as a marker of aggressive behavior in female breast cancer. The aim of this study is to investigate the role of the X chromosome in male breast cancer. Twenty cases of male breast invasive ductal carcinoma were retrieved and compared with 10 cases of gynecomastia. Cases were tested by fluorescence in situ hybridization to assess a cytogenetic profile for the X chromosome. The X chromosome status was compared with histopathologic features and stage at presentation. All MBC cases harbored an X chromosome gain (100%) in a variable percentage of neoplastic cells, ranging from 31% to 85% (mean, 59%). On the contrary, all cases of gynecomastia showed wild X chromosome asset. The patients' age at surgery and tumor grading showed a statistically significant correlation (P = .0188-.04), with the percentages of neoplastic cells showing an X chromosome gain. These data suggest that this X chromosome gain plays a role in the neoplastic transformation of male breast epithelial cells.

Ressl N, Oberndorfer S
Multiple calcified brain metastases in a man with invasive ductal breast cancer.
BMJ Case Rep. 2015; 2015 [PubMed] Related Publications
We report a case of a 52-year-old Caucasian man with invasive ductal carcinoma of the breast. One year after initial diagnosis, he developed a generalised epileptic seizure and neuroimaging showed multiple, calcified intracerebral lesions. Owing to these atypical cerebral imaging findings, comprehensive serological and cerebrospinal fluid analysis was conducted and a latent toxoplasmosis was suspected. In order to distinguish between metastases and an infectious disease, a cerebral biopsy was performed, which verified brain metastases. The patient received whole-brain radiotherapy. The last cerebral CT scan, 18 months later showed stable disease. Calcification of brain metastases in patients with breast cancer is very rare. Owing to their non-characteristic radiological appearance with a lack of contrast enhancement, diagnosis of metastases can be difficult. Infectious diseases should be considered within the diagnostic work up. Owing to possible pitfalls, we recommend a widespread differential diagnostic work up in similar cases, and even in cases with a confirmed primary tumour.

Hagelstrom RT, Ford J, Reiser GM, et al.
Breast Cancer and Non-Hodgkin Lymphoma in a Young Male with Cowden Syndrome.
Pediatr Blood Cancer. 2016; 63(3):544-6 [PubMed] Related Publications
Male breast cancer (MBC) is unusual, especially in young adults. Most cases of MBC as a secondary malignancy relate to the previous treatment with ionizing radiation. MBC can be associated with mutations in hereditary cancer predisposition syndrome genes (i.e., BRCA2); however, no such association has been reported in patients with Cowden syndrome (involving the phosphatase and tensin homolog [PTEN] gene). We describe a patient with Cowden syndrome who was initially diagnosed with B-cell lymphoblastic lymphoma at the age of 7 years, then MBC at the age of 31 years, and never received radiation therapy.

Ruckart PZ, Bove FJ, Shanley E, Maslia M
Evaluation of contaminated drinking water and male breast cancer at Marine Corps Base Camp Lejeune, North Carolina: a case control study.
Environ Health. 2015; 14:74 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Solvents contaminated drinking water supplies at Marine Corps Base Camp Lejeune during 1950s-1985.
METHODS: We conducted a case-control study among Marines to evaluate associations between residential exposure to contaminated drinking water at Camp Lejeune and male breast cancer risk. The study included 71 male breast cancer cases and 373 controls identified from the Department of Veteran's Affairs (VA) cancer registry whose military personnel records were available. Controls were selected from cancers not known to be associated with solvent exposure and included 270 skin cancers, 71 mesotheliomas, and 32 bone cancers. Base assignment and risk factor information came from military personnel and VA records. Groundwater contaminant fate/transport and distribution system models provided monthly estimated residential contaminant levels. We conducted exact logistic regression using the 50th percentile level among exposed controls to create low and high exposure categories. We calculated 95% confidence intervals (CIs) to indicate precision of effect estimates. Exploratory analyses used proportional hazards methods to evaluate associations between exposures and age at diagnosis.
RESULTS: After adjusting for age at diagnosis, race, and service in Vietnam, the odds ratio (OR) for ever stationed at Camp Lejeune was 1.14 (95% CI: 0.65, 1.97). Adjusted ORs for high residential cumulative exposures to tetrachloroethylene (PCE), t-1,2 dichloroethylene (DCE), and vinyl chloride were 1.20 [95% CI: 0.16-5.89], 1.50 [95% CI: 0.30-6.11], 1.19 [95% CI: 0.16-5.89], respectively, with a monotonic exposure response relationship for PCE only. However these results were based on two or three cases in the high cumulative exposure categories. Ever stationed at Camp Lejeune and high cumulative exposures to trichloroethylene (TCE), PCE, DCE and vinyl chloride were associated with earlier age at onset for male breast cancer; hazard ratios ranged from 1.4-2.7 with wide confidence intervals for cumulative exposure variables.
CONCLUSION: Findings suggested possible associations between male breast cancer and being stationed at Camp Lejeune and cumulative exposure to PCE, DCE, and vinyl chloride. TCE, PCE, DCE and vinyl chloride cumulative exposures showed possible associations with earlier age at onset of male breast cancer. However, this study was limited by small numbers of cases in high exposure categories.

Seo KJ, Kim JJ
Primary cutaneous apocrine gland carcinoma from areolar tissue in a male patient with gynecomastia: a case report.
J Cardiothorac Surg. 2015; 10:111 [PubMed] Free Access to Full Article Related Publications
Primary cutaneous apocrine gland carcinoma, which is a type of sweat gland carcinoma, is an extremely rare type of cancer. Clinical courses of this type of cancer usually progress slowly but can, occasionally, be associated with rapid progression. This case report describes a 53-year-old Korean man with primary cutaneous apocrine gland carcinoma that arose from an apocrine gland in the areola tissue. The patient visited our hospital because of a large, painful chest wall mass beneath the right nipple. The mass had been present for more than eight years but had grown rapidly over the past few months. The patient was initially diagnosed with a benign cystic mass, and we performed a wide excision with a clear margin and without lymph node dissection. The mass was a well-encapsulated cystic lesion that contained old blood material, and there was no invasion into the surrounding tissue. The final pathology showed that the mass was a primary cutaneous apocrine gland carcinoma that arose from the areola apocrine sweat gland, not from the breast parenchymal tissue. Herein, we report an extremely rare chest wall mass unfamiliar to thoracic surgeons.

Kim JG, Kim SY, Jung HY, et al.
Extremely rare borderline phyllodes tumor in the male breast: a case report.
Clin Imaging. 2015 Nov-Dec; 39(6):1108-11 [PubMed] Related Publications
Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation.

Yu XF, Yang HJ, Yu Y, et al.
A Prognostic Analysis of Male Breast Cancer (MBC) Compared with Post-Menopausal Female Breast Cancer (FBC).
PLoS One. 2015; 10(8):e0136670 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Male breast cancer (MBC) is known to be rare compared with female breast cancer (FBC) and to account for only 1% of all breast cancers. To date, male patients diagnosed with breast cancer are normally treated based on the guidelines for FBC. Specifically, studies have found that diagnosing and treating MBC patients under the guidelines for the treatment of post-menopausal FBC are more favorable than are those of pre/peri-menopausal FBC from a physiological perspective because MBC and post-menopausal FBC patients show high estrogen receptor (ER) expression in the tumor and low estrogen expression in the body. In this medical study, we aimed to examine whether MBC actually has the same prognosis as post-menopausal FBC.
METHOD: We identified MBC patients who were diagnosed as operable and who completed clinical treatment and we used follow-up data that were collected from January 2001 to January 2011. Each MBC patient was paired with four FBC patients who were diagnosed within the same period (two were pre/peri-menopausal, and two were post-menopausal). We compared disease-free survival (DFS) and overall survival (OS) among three groups, i.e., pre/peri-menopausal FBC (group A), post-menopausal FBC (group B) and MBC (group M), using the Kaplan-Meier method and a Cox proportional hazards regression model. We also evaluated the clinical characteristics of breast cancer patients using t-tests and chi-square tests. We used ten consecutive years of data that were collected at Zhejiang Provincial Cancer Hospital.
RESULTS: We identified 91 MBC cases for group M, 182 FBC cases for group A and 182 FBC cases for group B. The median follow-up period was 112 months. MBC cases were much more frequently ER positive than those of group A and group B (p<0.01); a similar trend was also found for progesterone (PR)-positive cases (p<0.01). The MBC group showed much lower human epidermal growth factor receptor-2 (HER2) expression than did the other groups (p<0.01). The 10-year OS rates were 79.1% for group M (72/91), 79.1% (144/182) for group A, and 87.9% (160/182) for group B, log-rank test indicated that group M had similar mean OS time as group A and group B (GourpM vs group A: p = 0.709; group M vs group B: p = 0.042). The Cox proportional hazards regression model indicated that pre/peri-menopausal FBC had similar DFS (hazard ratio (HR) = 0.706, p = 0.262) and OS (HR = 1.029, p = 0.941) values compared with MBC, whereas post-menopausal FBC had higher DFS (HR = 0.454, p = 0.004) and OS (HR = 0.353, p = 0.003) values than did MBC.
CONCLUSION: Based on this study, we can conclude that MBC displayed higher ER- and PR-positive expression and lower HER2-positive expression than both post-menopausal and pre/peri-menopausal FBC. However, the DFS and OS values of MBC were similar to those of pre/peri-menopausal FBC and were worse than were those of post-menopausal FBC.

Di Lauro L, Barba M, Pizzuti L, et al.
Androgen receptor and antiandrogen therapy in male breast cancer.
Cancer Lett. 2015; 368(1):20-5 [PubMed] Related Publications
Cancers arising in the male breast are uncommon. Male breast cancer is a hormone-driven disease that often expresses the estrogen receptor, and antiestrogen therapy represents the mainstay of treatment. Paradoxically, the advent of a wave of antiestrogens eclipsed the therapeutic potential of alternative therapeutic options. At the beginning of the hormonal therapy era the administration of antiandrogens to metastatic male breast cancer patients was proposed. Ever since the use of these compounds has largely been neglected. A therapeutic role for antiandrogens has been envisioned again in recent years. First, molecular characterization efforts pointed to the androgen receptor as a potential therapeutic target. Second, the development of aromatase inhibitors unexpectedly raised the need for neutralizing androgens in order to tackle endocrine feedback mechanisms responsible for acquired resistance. We herein provide an overview of molecular studies where the androgen receptor was investigated at the genomic, transcriptomic or phenotypic level. We then discuss androgens in the context of the endocrine networks nourishing male breast cancer. Finally, clinical evidence on antiandrogens is summarized along with strategies should be implemented to improve the medical management of these patients.

Silvestri V, Rizzolo P, Scarnò M, et al.
Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: results from a multicenter study in Italy.
Eur J Cancer. 2015; 51(16):2289-95 [PubMed] Related Publications
Increasing evidence indicates that common genetic variants may contribute to the heritable risk of breast cancer (BC). In this study, we investigated whether single nucleotide polymorphisms (SNPs), within the 8q24.21 multi-cancer susceptibility region and within BC-associated loci widespread in the genome, may influence the risk of BC in men, and whether they may be associated with specific clinical-pathologic characteristics of male BC (MBC). In the frame of the ongoing Italian Multicenter Study on MBC, we performed a case-control study on 386 MBC cases, including 50 BRCA1/2 mutation carriers, and 1105 healthy male controls, including 197 unaffected BRCA1/2 mutation carriers. All 1491 subjects were genotyped by Sequenom iPLEX technology for a total of 29 susceptibility SNPs. By logistic regression models, we found a significant association with MBC risk for five SNPs: rs1562430 (p=0.002) and rs445114 (p=0.026) both within the 8q24.21 region; rs1011970/9p21.3 (p=0.011), rs614367/11q13.3 (p=0.016) and rs1314913/14q24.1 (p<0.0001). Differences in the distribution of rs614367/11q13.3 genotypes according to oestrogen receptor (ER) status (p=0.006), and of rs1011970/9p21.3 genotypes according to human epidermal growth factor receptor 2 (HER2) status (p=0.002) emerged. Association of rs1011970/9p21.3 risk genotype with HER2+MBC was confirmed by a multivariate analysis. rs1314913/14q24.1 was associated with increased MBC risk in analyses restricted to male BRCA1/2 mutation carriers (p=0.041). In conclusion, we provided the first evidence that the 8q24.21 region is associated with MBC risk. Furthermore, we showed that the SNPs rs1562430/8q24.21 and rs1314913/14q24.1 strongly influence BC risk in men and suggested that the SNP rs1314913/14q24.1 may act as a risk modifier locus in male BRCA1/2 mutation carriers.

Hamilton BK, Rybicki L, Abounader D, et al.
Long-term survival after high-dose chemotherapy with autologous hematopoietic cell transplantation in metastatic breast cancer.
Hematol Oncol Stem Cell Ther. 2015; 8(3):115-24 [PubMed] Related Publications
OBJECTIVE/BACKGROUND: The most common indication for high-dose chemotherapy (HDC) and autologous hematopoietic cell transplantation (AHCT) in the 1990s was breast cancer. Several randomized trials and a more recent meta-analysis failed to show a survival benefit for AHCT in metastatic breast cancer (MBC); however, they demonstrated a better-than-expected 10-year to 15-year survival in 5-15% of patients. We thus evaluated the long-term results of treatment with HDC and AHCT in MBC at our institution.
METHODS: From 1984 to 2000, 285 patients underwent AHCT for MBC. The patient characteristics were collected through the Cleveland Clinic, United Transplant Database. A retrospective review of the medical records of the long-term surviving breast-cancer patients treated with HDC and AHCT was conducted.
RESULTS: With a median follow-up of 169 months, 34 (12%) remain alive. Of the 251 patients who died, 218 (87%) died of metastatic disease. A comparison by age (<50 years and >50 years) and hormonal status did not demonstrate any differences in relapse (p=.33 and p=.32, respectively) or survival (p=.13 and p=.42). Of the 34 long-term survivors, sufficient data were available on 28 patients, and further evaluation revealed that the majority had a primary or locally recurrent oligometastatic disease.
CONCLUSION: This retrospective evaluation of patients who underwent AHCT for MBC demonstrates long-term survival in a small subset of patients, primarily those with primary or recurrent oligometastatic disease. Oligometastatic breast cancer is a distinct entity within MBC, which may be curable with multimodality therapy. We thus conclude there remains no overall-survival benefit to HDC in MBC.

Khan MH, Allerton R, Pettit L
Hormone Therapy for Breast Cancer in Men.
Clin Breast Cancer. 2015; 15(4):245-50 [PubMed] Related Publications
Breast cancer in men is rare, but its incidence is increasing, in keeping with the aging population. The majority of breast cancers in men are estrogen receptor positive. There is a paucity of clinical trials to inform practice, and much has been extrapolated from breast cancer in women. Hormone therapy represents the mainstay of adjuvant and palliative therapy but may have contraindications or poor tolerability. We review the evidence for choice of hormone therapy in both the adjuvant and palliative setting in breast cancer in men.

Waisbren J, Uthe R, Siziopikou K, Kaklamani V
BRCA 1/2 gene mutation and gastrointestinal stromal tumours: a potential association.
BMJ Case Rep. 2015; 2015 [PubMed] Related Publications
Mutations of the BRCA1/2 genes have been described in association with a number of malignancies including cancers of the breast, ovary, prostate and stomach, but have never been described in relation to gastrointestinal stromal tumours (GIST). We describe a patient with a BRCA2 8642del3insC mutation who developed prostate cancer, breast cancer and GIST. GIST has been shown to be associated with a number of malignancies, including some of the common BRCA1/2-related cancers, but it has never been associated with BRCA1/2 gene mutations. This report highlights the potential association between BRCA1/2 mutations and GIST, and aims to raise awareness for further genetic screening in GIST patients.

Robinson D, Garmo H, Holmberg L, Stattin P
5-α reductase inhibitors, benign prostatic hyperplasia, and risk of male breast cancer.
Cancer Causes Control. 2015; 26(9):1289-97 [PubMed] Free Access to Full Article Related Publications
PURPOSE: 5-α reductase inhibitors (5-ARI) have been suggested to increase the risk of male breast cancer. The aim of this study was to study the risk of breast cancer in men on 5-ARI, in men with benign prostatic hyperplasia (BPH) not on 5-ARI, and in men without BPH.
METHODS: We performed a population-based cohort study in Sweden with data from The Prescribed Drug Register, The Patient Register, and The Cancer Register. Men on 5-ARI, men on α-blockers, or men who had undergone a transurethral resection of the prostate (TUR-P) prior to or during 2006-2008 were included as exposed to BPH and a specific treatment thereof. For each exposed man, five unexposed men were selected. Risk of breast cancer was calculated in Cox proportional hazard models.
RESULTS: There were 124,183 exposed men and 545,293 unexposed men, and during follow-up (median 6 years), 99 men with breast cancer were diagnosed. Compared to unexposed men, men on 5-ARI had a hazard ratio (HR) of breast cancer of 0.74 (95% confidence interval (CI) 0.27-2.03), men on α-blockers had HR 1.47 (95% CI 0.73-2.95), and men with a TUR-P had HR 1.99 (95% CI 1.05-3.75).
CONCLUSION: No increased risk of breast cancer was observed for men on 5-ARI. However, the increased risk of breast cancer among men who had undergone a TUR-P, a strong indicator of BPH, suggests that the endocrine milieu conducive to BPH is associated with male breast cancer.

Motofei IG, Rowland DL, Popa F, et al.
A Pilot Study on Tamoxifen Sexual Side Effects and Hand Preference in Male Breast Cancer.
Arch Sex Behav. 2015; 44(6):1589-94 [PubMed] Related Publications
Recent clinical and imaging studies suggest that sex hormones modulate sexuality according to a psychophysiologic process of lateralization of the brain, with androgens playing a greater role in sexual functioning of left hemibrain/right handedness and estrogens possibly for right hemibrain/left handedness. Based on this perspective, the current study attempted to specify the relationship between hand preference, estrogens, and sexual function in subjects with male breast cancer, taking into account the sexual side effects of tamoxifen as the agent for inhibiting estrogen action. Twenty-eight Romanian men-17 right-handed and 11 left-handed-undergoing treatment with tamoxifen for male breast cancer participated in this study. These men were assessed both prior to and during tamoxifen treatment using the International Index of Erectile Function, a standardized instrument used for the evaluation of various aspects of sexual functioning, including erectile function (EF), orgasmic function (OF), sexual desire (SD), and overall functioning (OF). A main effect for handedness was found on EF, OF, SD, and OS scales, with right-handed men showing higher functioning than left-handed men. Regarding interaction effects, the left-handed group of men showed greater decreased sexual functioning during tamoxifen (on three subscales: OF, SD, OS) compared to right-handed men. Further research should be conducted in order to support and refine this potential lateralized process of sexual neuromodulation within the brain.

He M, Liu H, Jiang Y
A Case Report of Male Occult Breast Cancer First Manifesting as Axillary Lymph Node Metastasis With Part of Metastatic Mucinous Carcinoma.
Medicine (Baltimore). 2015; 94(25):e1038 [PubMed] Free Access to Full Article Related Publications
Occult breast cancer (OBC) is a type of breast cancer without any symptoms in the breast (no primary cancer lesion is found in either breast on a physical examination or imaging examination such as ultrasound and mammography). The incidence of OBC is rare in females, whereas in males, there are few cases of breast cancer, and the rate of OBC is very low. This is the first time report a case of male OBC first manifested as axillary metastasis, of which the pathological results showed moderately differentiated adenocarcinoma with part of metastatic mucinous carcinoma.A 40-year-old male patient presenting palpable masses in his left axillary on physical and imaging examination revealed unremarkable despite of multiple swollen lymph nodes in the left axillary, and the resected sample showed metastatic adenocarcinoma with part of metastatic mucinous carcinoma. Based on immunohistochemical analysis, positive of estrogen receptor (ER), progesterone receptor (PR), and human epidermal receptor 2 (Her-2), it was identified as an OBC.This is the fourth case report of male OBC in the literature; 1 case was reported in China in 2008, and it was metastatic infiltrating ductal carcinoma, and 2 cases were reported in Korea in 2012, one of which was reported as metastatic carcinoma and the other was metastatic adenocarcinoma; however, our case was a moderately differentiated adenocarcinoma with part of mucinous carcinoma. Our case of male OBC could metastasize to supraclavicular region and lung in addition to axillary lymph nodes, and the prognosis was relatively poor compared to the 3 cases reported before.The aim of this case report is to introduce the imaging, pathological features, and management of a rare male OBC.

Li G, Zhong X, Yao J, et al.
Secretory breast carcinoma in a 41-year-old man with long-term follow-up: a special report.
Future Oncol. 2015; 11(12):1767-73 [PubMed] Related Publications
Secretory breast carcinoma (SBC) is a rare tumor that is particularly rare in male adults. To our knowledge, only 28 previous male cases of secretory breast carcinoma have been reported. The present a case of secretory breast carcinoma has the longest symptom duration of (40 years) in a male individual until now. Typically, the clinical features and treatment of male SBC are similar with female SBC. The ETV6-NTRK3 fusion gene is a specific genetic alteration in SBC. When compared to other types of male breast cancer, patients with male secretory breast cancer are much younger, and have a lower rate of estrogen/progesterone hormone receptor positivity. Modified radical mastectomy has been favored as a therapeutic approach in all female SBC, male SBC and other types of male breast cancer. [corrected].

Yen PP, Sinha N, Barnes PJ, et al.
Benign and Malignant Male Breast Diseases: Radiologic and Pathologic Correlation.
Can Assoc Radiol J. 2015; 66(3):198-207 [PubMed] Related Publications
Male breast disease comprises a wide spectrum of benign and malignant processes. We present the spectrum of diseases encountered at our institution over the past 7 years (2007-2013) and correlate their radiological and histopathological appearances. Gynaecomastia is the most frequently encountered disease due to its association with a variety of causes. Male breast malignancies, though rare, must be considered. The most frequently encountered pathological characteristic is invasive and the predominant histologic subtypes are infiltrating ductal carcinomas.

Ding J, Jiang L, Gan Y, Wu W
A rare case of secretory breast carcinoma in a male adult with axillary lymph node metastasis.
Int J Clin Exp Pathol. 2015; 8(3):3322-7 [PubMed] Free Access to Full Article Related Publications
Secretory breast carcinoma is a rare tumor originally described in children but occurring equally in adult population, especially in women. This unusual subtype has a generally favorable prognosis, although several cases have been described in adults with increased aggressiveness and a risk of metastases even death. So far, merely ten cases of secretory breast carcinoma with metastatic axillary lymph node in male were reported. Here, we describe the eleventh case, a 24-years-old male who presented with a painless mass in the right breast was diagnosed to be "secretary breast carcinoma", and subsequently underwent modified radical mastectomy and adjuvant chemotherapy.

Humphries MP, Jordan VC, Speirs V
Obesity and male breast cancer: provocative parallels?
BMC Med. 2015; 13:134 [PubMed] Free Access to Full Article Related Publications
While rare compared to female breast cancer the incidence of male breast cancer (MBC) has increased in the last few decades. Without comprehensive epidemiological studies, the explanation for the increased incidence of MBC can only be speculated. Nevertheless, one of the most worrying global public health issues is the exponential rise in the number of overweight and obese people, especially in the developed world. Although obesity is not considered an established risk factor for MBC, studies have shown increased incidence among obese individuals. With this observation in mind, this article highlights the correlation between the increased incidence of MBC and the current trends in obesity as a growing problem in the 21(st) century, including how this may impact treatment. With MBC becoming more prominent we put forward the notion that, not only is obesity a risk factor for MBC, but that increasing obesity trends are a contributing factor to its increased incidence.

Hartkopf AD, Taran FA, Walter CB, et al.
Detection and prevalence of disseminated tumor cells from the bone marrow of early stage male breast cancer patients.
Breast Cancer Res Treat. 2015; 152(1):51-5 [PubMed] Related Publications
Male breast cancer (mBC) is a rare entity. As detection of disseminated tumor cells (DTCs) in the bone marrow of females with early stage breast cancer is a promising prognostic marker, we aimed to determine the prevalence and prognostic value of DTCs in mBC. Bone marrow aspirates were collected from male patients undergoing primary surgery for early stage breast cancer (T1-4, N0-2, M0) at Tuebingen University, Germany, between January 2001 and April 2015. DTCs were identified by immunocytochemistry (pancytokeratin antibody A45/B-B3) and cytomorphology. 24 patients with mBC were included into the analysis. DTCs were detected in four of these (17 %). There was no significant association between the DTC status and any other clinicopathological parameter. Also, no significant impact of the DTC status on DFS or OS could be observed. DTCs are detectable in patients with early stage mBC. The detection rate is comparable to that in women. No associations between DTCs and clinicopathological features or prognosis were observed, which is most likely due to the small sample size. The detection of DTCs in male patients with early stage breast cancer emphasizes the transmission of future clinical applications for DTCs from women to men.

Di Lauro L, Pizzuti L, Barba M, et al.
Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: results from a pooled analysis.
J Hematol Oncol. 2015; 8:53 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Male breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. We conducted this study to provide more concrete ground on the use of gonadotropin-releasing hormone analogues in this setting.
METHODS: We herein present results from a pooled analysis including 60 metastatic male breast cancer patients treated with either an aromatase inhibitor or cyproterone acetate as a monotherapy (23 patients) or combined with a gonadotropin-releasing hormone analogue (37 patients).
RESULTS: Overall response rate was 43.5% in patients treated with monotherapy and 51.3% with combination therapy (p = 0.6). Survival outcomes favored combination therapy in terms of median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year progression-free survival rate (43.2% versus 21.7%; p = 0.05), median overall survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate (64.9% versus 43.5%; p = 0.05).
CONCLUSIONS: In metastatic male breast cancer patients, the combined use of gonadotropin-releasing hormone analogues and aromatase inhibitors or antiandrogens seems to be associated with greater efficacy, particularly in terms of survival outcomes, compared with monotherapy. Collectively, these results encourage considering these agents in the metastatic setting.

Brinton LA, Key TJ, Kolonel LN, et al.
Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk.
J Clin Oncol. 2015; 33(18):2041-50 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones.
PATIENTS AND METHODS: Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes.
RESULTS: Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men.
CONCLUSION: Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers.

Abreu MH, Gomes M, Menezes F, et al.
CYP2D6*4 polymorphism: A new marker of response to hormonotherapy in male breast cancer?
Breast. 2015; 24(4):481-6 [PubMed] Related Publications
BACKGROUND: Tamoxifen remains the standard hormonotherapy for Male breast cancer patients (MBC). Previous studies, in women, tried to evaluate the impact of CYP2D6 polymorphisms in tamoxifen efficacy with conflicting results. Herein we analyze the relation between CYP2D6*4 polymorphism and survival in MBC patients.
PATIENTS AND METHODS: Fifty-three patients, proposed to tamoxifen in adjuvant setting, were enrolled. Clinical information was collected from records and histological revision with additional immunochemistry analysis was done to better characterize the tumors. Comprehensive CYP2D6*4 genotyping from blood or tumor tissue was performed and translated into two predicted metabolic activity groups.
RESULTS: Patients included in the two CYP2D6*4 groups did not differ concerning to age, histological characteristics, and primary treatments performed. Median age at diagnosis was 63 years-old and patients were submitted at least to mastectomy and adjuvant hormonotherapy. Recurrence was observed in 7 patients (13.2%) and 13 patients (25.5%) died with a 5-year disease-free survival of 86.2%. The poorer metabolizer group had a high risk for recurrence (p = 0.034) and this outcome effect remains in different subgroups: in tumors larger than 2 cm (p < 0.001), nodal status, N0 vs N+ (p = 0.04) and in advanced stage, stage III (p < 0.001). Poorer metabolizer patients had also a worse overall survival when tumors were larger than 2 cm (p = 0.03).
CONCLUSIONS: In our series, there was an association between CYP2D6*4 polymorphism and a probability of recurrence, with a consistent effect in risk groups defined by classic prognostic factors. Multicentric studies with larger samples are needed to validate these results.

Leporati P, Fonte R, de Martinis L, et al.
A male patient with acromegaly and breast cancer: treating acromegaly to control tumor progression.
BMC Cancer. 2015; 15:397 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Acromegaly is a rare disease associated with an increased risk of developing cancer.
CASE PRESENTATION: We report the case of a 72-year-old man who was diagnosed with acromegaly (IGF-1 770 ng/ml) and breast cancer. Four years before he suffered from a colon-rectal cancer. Pituitary surgery and octreotide-LAR treatment failed to control acromegaly. Normalization of IGF-1 (97 ng/ml) was obtained with pegvisomant therapy. Four years after breast cancer surgery, 2 pulmonary metastases were detected at chest CT. The patient was started on anastrozole, but, contrary to medical advice, he stopped pegvisomant treatment (IGF-I 453 ng/ml). Four months later, chest CT revealed an increase in size of the metastatic lesion of the left lung. The patient was shifted from anastrozole to tamoxifen and was restarted on pegvisomant, with normalization of serum IGF-1 levels (90 ng/ml). Four months later, a reduction in size of the metastatic lesion of the left lung was detected by CT. Subsequent CT scans throughout a 24-month follow-up showed a further reduction in size and then a stabilization of the metastasis.
CONCLUSIONS: This is the first report of a male patient with acromegaly and breast cancer. The clinical course of breast cancer was closely related to the metabolic control of acromegaly. The rapid progression of metastatic lesion was temporally related to stopping pegvisomant treatment and paralleled a rise in serum IGF-1 levels. Normalization of IGF-1 after re-starting pegvisomant impressively reduced the progression of metastatic breast lesions. Control of acromegaly is mandatory in acromegalic patients with cancer.

Masci G, Caruso M, Caruso F, et al.
Clinicopathological and Immunohistochemical Characteristics in Male Breast Cancer: A Retrospective Case Series.
Oncologist. 2015; 20(6):586-92 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Due to its rarity, male breast cancer (mBC) remains an inadequately characterized disease, and current evidence for treatment derives from female breast cancer (FBC).
METHODS: We retrospectively analyzed the clinicopathological characteristics, treatment patterns, and outcomes of mBCs treated from 2000 to 2013.
RESULTS: From a total of 97 patients with mBC, 6 (6.2%) with ductal in situ carcinoma were excluded, and 91 patients with invasive carcinoma were analyzed. Median age was 65 years (range: 25-87 years). Estrogen receptors were positive in 88 patients (96.7%), and progesterone receptors were positive in 84 patients (92.3%). HER-2 was overexpressed in 13 of 85 patients (16%). Median follow-up was 51.5 months (range: 0.5-219.3 months). Five-year progression-free survival (PFS) was 50%, whereas overall survival (OS) was 68.1%. Patients with grades 1 and 2 presented 5-year PFS of 71% versus 22.5% for patients with grade 3 disease; 5-year OS was 85.7% for patients with grades 1 and 2 versus 53.3% of patients with grade 3. Ki-67 score >20% and adjuvant chemotherapy were also statistically significant for OS on univariate analyses. Twenty-six of 87 patients (29.8%) experienced recurrent disease and 16 of 91 patients (17.6%) developed a second neoplasia.
CONCLUSION: Male breast cancer shows different biological patterns compared with FBC, with higher positive hormone-receptor status and lower HER-2 overexpression. Grade 3 and Ki-67 >20% were associated with shorter OS.
IMPLICATIONS FOR PRACTICE: There is little evidence that prognostic features established in female breast cancer, such as grading and Ki-67 labeling index, could be applied to male breast cancer as well. This study found that grade 3 was associated with shorter overall survival and a trend for Ki-67 >20%; this could help in choosing the best treatment option in the adjuvant setting. Many questions remain regarding the impact of HER-2 positivity on survival and treatment with adjuvant anti-HER-2 therapy. Regarding metastatic male breast cancer, the results suggest that common regimens of chemo-, endocrine and immunotherapy used in female breast cancer are safe and effective for men. Male breast cancer patients show a higher incidence of second primary tumors, especially prostate and colon cancers and should therefore be carefully monitored.

Mitri ZI, Jackson M, Garby C, et al.
BRCAPRO 6.0 Model Validation in Male Patients Presenting for BRCA Testing.
Oncologist. 2015; 20(6):593-7 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: BRCAPRO is a risk assessment model to estimate the risk of carrying a BRCA mutation. BRCA mutation carriers are at higher risk of developing breast, ovarian, pancreatic, and prostate cancer. BRCAPRO was developed for women and found to be superior to other risk assessment models. The present study evaluated the validity of BRCAPRO at predicting the risk of male patients carrying a BRCA mutation.
PATIENTS AND METHODS: A total of 146 men who presented for genetic counseling and testing from February1997 to September 2011, and their test results were included in the present study. BRCAPRO risk assessment for all patients was calculated using the BRCAPRO clinical CancerGene assessment software.
RESULTS: The mean age at presentation was 57 years. Of the 146 patients, 48 had breast cancer, 18 had pancreatic cancer, 39 had prostate cancer, 27 had other primary cancers, and 37 had no cancer. Fifty patients (34%) tested positive for a BRCA mutation (22 BRCA1, 27 BRCA2, and 1 BRCA1 and BRCA2). The mean BRCAPRO score for all patients was 24.96%. The BRCAPRO score was significantly higher for patients who tested positive for a BRCA mutation (46.19% vs. 13.9%, p < .01). The area under the receiver operating characteristics curve was 0.83 for all patients for the BRCAPRO score to predict the risk of carrying a BRCA mutation. At a cutoff point of 30.02%, the sensitivity, specificity, positive predictive value, and negative predictive value were 0.74, 0.81, 0.67, and 0.86, respectively.
CONCLUSION: BRCAPRO appears to be a valid risk assessment tool for determining the risk of carrying a BRCA mutation in men.
IMPLICATIONS FOR PRACTICE: Men carrying genetic mutations in the BRCA gene have a greater risk than the general population of developing certain types of cancer, including breast, pancreatic, and prostate cancer. BRCAPRO is a risk assessment model that predicts the risk of carrying a BRCA mutation. The present study aimed at validating BRCAPRO for use with men seen for genetic counseling, whether affected by cancer or not. The data available for 146 patients revealed that BRCAPRO was effective at identifying patients at risk of BRCA mutation. These findings could help in identifying a subset of high-risk patients who should proceed to genetic testing.

Sineshaw HM, Freedman RA, Ward EM, et al.
Black/White Disparities in Receipt of Treatment and Survival Among Men With Early-Stage Breast Cancer.
J Clin Oncol. 2015; 33(21):2337-44 [PubMed] Related Publications
PURPOSE: To examine the extent of black/white disparities in receipt of treatment and survival for early-stage breast cancer in men age 18 to 64 and ≥ 65 years.
PATIENTS AND METHODS: We identified 725 non-Hispanic black (black) and 5,247 non-Hispanic white (white) men diagnosed with early-stage breast cancer from 2004 to 2011 in the National Cancer Data Base. We used multivariable logistic regression and calculated standardized risk ratios to predict receipt of treatment and a proportional hazards model to estimate overall hazard ratios (HRs) in black versus white men age 18 to 64 and ≥ 65 years, separately.
RESULTS: Receipt of treatment was remarkably similar between blacks and whites in both age groups. Black and white older men had lower receipt of chemotherapy (39.2% and 42.0%, respectively) compared with younger patients (76.7% and 79.3%, respectively). Younger black men had a 76% higher risk of death than younger white men after adjustment for clinical factors only (HR, 1.76; 95% CI, 1.11 to 2.78), but this difference significantly diminished after subsequent adjustment for insurance and income (HR, 1.37; 95% CI, 0.83 to 2.24). In those age ≥ 65 years, the excess risk of death in blacks versus whites was nonsignificant and not affected by adjustment for covariates.
CONCLUSION: The excess risk of death in black versus white men diagnosed with early-stage breast cancer was largely confined to those age 18 to 64 years and became nonsignificant after adjustment for differences in insurance and income. These findings suggest the importance of improving access to care in reducing racial disparities in male breast cancer mortality.

Lacle MM, Moelans CB, Kornegoor R, et al.
Chromosome 17 copy number changes in male breast cancer.
Cell Oncol (Dordr). 2015; 38(3):237-45 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Overall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of chromosome 17 alterations in small MBC cohorts.
METHODS: Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to detect and characterize copy number changes on chromosome 17 in a cohort of 139 MBC. The results obtained were compared to those in FBC, and were correlated with clinicopathological features and patient outcome data.
RESULTS: We observed a lower frequency of chromosome 17 copy number changes with less complex rearrangement patterns in MBC compared to FBC. Chromosome 17 changes in MBC included gains of 17q and losses of 17p. Whole chromosome 17 polyploidies were not encountered. Two recurrent chromosome 17 amplicons were detected: on 17q12 (encompassing the NEUROD2, HER2, GRB7 and IKZF3 gens) and on 17q23.1 (encompassing the MIR21 and RPS6KB1 genes). Whole arm copy number gains of 17q were associated with decreased 5 year survival rates (p = 0.010). Amplification of HER2 was associated with a high tumor grade, but did not predict patient survival. Although copy number gains of HER2 and NEUROD2 were associated with a high tumor grade, a high mitotic count and a decreased 5 year survival rate (p = 0.015), only tumor size and NEUROD2 copy number gains emerged as independent prognostic factors.
CONCLUSIONS: In MBC chromosome 17 shows less complex rearrangements and fewer copy number changes compared to FBC. Frequent gains of 17q, encompassing two distinct amplicons, and losses of 17p were observed, but no whole chromosome 17 polyploidies. Only NEUROD2 gains seem to have an independent prognostic impact. These results suggest different roles of chromosome 17 aberrations in male versus female breast carcinogenesis.

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