Male Breast Cancer
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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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Breast Cancer (general resources)

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Latest Research Publications

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

Downey CL, Simpkins SA, White J, et al.
The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer.
Br J Cancer. 2014; 110(7):1744-7 [PubMed] Article available free on PMC after 01/04/2015 Related Publications
BACKGROUND: A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour-stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas.
METHODS: TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed.Results:Tumours with ≥49% stroma were associated with better survival in female (OS P=0.008, HR=0.2-0.7; RFS P=0.006, HR=0.1-0.6) and male breast cancer (OS P=0.005, HR=0.05-0.6; RFS P=0.01, HR=0.87-5.6), confirmed in multivariate analysis.
CONCLUSIONS: High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR.

Related: Breast Cancer

Kreiter E, Richardson A, Potter J, Yasui Y
Breast cancer: trends in international incidence in men and women.
Br J Cancer. 2014; 110(7):1891-7 [PubMed] Article available free on PMC after 01/04/2015 Related Publications
BACKGROUND: The age-standardised incidence of breast cancer varies geographically, with rates in the highest-risk countries more than five times those in the lowest-risk countries.
METHODS: We investigated the correlation between male (MBC) and female breast cancer (FBC) incidence stratified by female age-group (<50 years, and ≥50 years) and used Poisson regression to examine male incidence rate ratios according to female incidence rates.
RESULTS: Age-adjusted breast cancer incidence rates for males and females share a similar geographic distribution (Spearman's correlation=0.51; P<0.0001). A correlation with male incidence rates was found for the entire female population and for women aged 50 years and over. Breast cancer incidence rates in males aged <50 years were not associated with FBC incidence, whereas those in males aged 50 years were. MBC incidence displays a small 'hook' similar to the Clemmesen's hook for FBC, but at a later age than the female hook.
INTERPRETATION: Further investigation of possible explanations for these patterns is warranted. Although the incidence of breast cancer is much lower in men than in women, it may be possible to identify a cause common to both men and women.

Related: Breast Cancer

Mnif H, Charfi S, Abid N, Sallemi-Boudawara T
Mammary myofibroblastoma with leiomyomatous differentiation: case report and literature review.
Pathologica. 2013; 105(4):142-5 [PubMed] Related Publications
INTRODUCTION: Myofibroblastoma of the breast (MFB) is an unusual benign tumour that belongs to the family of benign spindle cell tumours of the mammary stroma. The detection of smooth muscle cells in MFB is explained by its histogenesis from CD34+ fibroblasts of mammary stroma capable of multidirectional mesenchymal differentiation, including smooth muscle.
AIMS: The purpose of this case is to highlight characteristics of this rare neoplasm. Immunohistochemical features, in MFB with predominant leiomyomatous differentiation, are provided to offer a practical approach to a correct diagnosis.
CASE REPORT: We report a right MFB in a 60-year-old male. The tumour was unusual due to its morphological features, with predominant leiomyomatous differentiation. Immunohistochemical findings, based on the negativity of h-caldesmon, helped in reaching a diagnosis.
CONCLUSION: The detection of leiomyomatous rather than myofibrolastic features in MFB may reflect only the predominant cell types of examined area, and this is not necessarily representative of the remaining tumour which may have a different basic cellular composition. Immunohistochemical expression of h-caldesmon is a reliable marker in distinguishing smooth muscle versus myofibrolastic cellular differentiation in spindle cells lesions of the breast.

Fernandes PH, Saam J, Peterson J, et al.
Comprehensive sequencing of PALB2 in patients with breast cancer suggests PALB2 mutations explain a subset of hereditary breast cancer.
Cancer. 2014; 120(7):963-7 [PubMed] Related Publications
BACKGROUND: This study sought to determine the prevalence of PALB2 mutations in a cohort referred for diagnostic testing for hereditary breast cancer.
METHODS: Sanger sequencing was used to analyze the entire coding region and flanking introns of PALB2 in anonymized DNA samples from 1479 patients. Samples were stratified into a "high-risk" group, 955 samples from individuals predicted to have a high probability of carrying a mutation in BRCA1 or BRCA2 based on their personal and family history, and a "lower-risk" group consisting of 524 samples from patients with breast cancer, but fewer risk factors for being a BRCA1 or BRCA2 mutation carrier. All patients were known to be negative for deleterious sequence mutations and large rearrangements in BRCA1 and BRCA2.
RESULTS: We identified 12 disease-associated PALB2 mutations among the 1479 patients (0.8%). The PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice-site mutation. The mutation prevalence for the high-risk population was 1.05% (95% CI = 0.5-1.92), whereas that for the lower-risk population was 0.38% (95% CI = 0.05-1.37). We identified 59 PALB2 variants of uncertain significance (VUS) among 57 of the 1479 patients (3.9%).
CONCLUSIONS: These results suggest that PALB2 mutations occur at a frequency of ~1% in patients with hereditary breast cancer.

Related: Breast Cancer PALB2

Aşchie M, Bălţătescu GI, Mitroi A
Clinico-pathological and molecular subtypes of male breast carcinoma according to immunohistochemistry.
Rom J Morphol Embryol. 2013; 54(3 Suppl):749-55 [PubMed] Related Publications
INTRODUCTION: Male breast carcinoma is a rare condition, but with a trend of increase frequency. In our study, we investigate the clinico-pathological features and overall survival at 35 male cases of primary invasive breast carcinoma correlated with molecular subtypes defined by immunohistochemical profile.
METHODS: Based on immunohistochemical expression profiles of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2) and Ki67, EGFR and CK5/6, the male breast cancers were classified into the following molecular subtypes: Luminal A, Luminal B, HER2+, triple negative and unclassified.
RESULTS: In our study, we identified 65.7% as Luminal A subtype and 28.6% as Luminal B subtype. The difference was represented by two (5.7%) cases of triple negative subtype, but due to low number of patients, no correlations or prognostic significance could be assessed in these cases. No HER2 or unclassified subtypes were identified.
CONCLUSIONS: Luminal A tumors are the most frequent subtype in MBC, with a better outcome than Luminal B subtype. We recorded high levels of ER and PR expression, which predict a better response to adjuvant hormonal therapy. At the time of diagnosis, most of the patients were aged and with an advance clinical stage, this requiring implementation of screening programs and increase education of population in order to an early detection.

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La Verde N, Collovà E, Lonardi S, et al.
Male breast cancer: clinical features and multimodal treatment in a retrospective survey analysis at Italian centers.
Tumori. 2013 Sep-Oct; 99(5):596-600 [PubMed] Related Publications
AIMS AND BACKGROUND: We report a collection of data about early breast cancer in male patients from 13 Italian institutions.
METHODS AND STUDY DESIGN: We obtained data from patient charts and performed statistical analysis. The primary end points were overall survival and disease-free survival.
RESULTS: A total of 205 men with invasive breast cancer was identified, with a median age of 66 years. Pathological characteristics were heterogeneous for T stage, N stage and HER2 status. Histological subtype was predominantly ductal infiltrating carcinoma. Most of them were hormone receptor positive. Mastectomy was the most common strategy. Postsurgical treatment was not standardized. Patients with large tumors were more likely to be treated with chemotherapy. Disease recurrence was associated with an ER+ and PR+ status.
CONCLUSIONS: We identified a correlation between relapse and hormone receptor expression, as is the case in female breast cancer.

Lee AJ, Cunningham AP, Kuchenbaecker KB, et al.
BOADICEA breast cancer risk prediction model: updates to cancer incidences, tumour pathology and web interface.
Br J Cancer. 2014; 110(2):535-45 [PubMed] Article available free on PMC after 21/01/2015 Related Publications
BACKGROUND: The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is a risk prediction model that is used to compute probabilities of carrying mutations in the high-risk breast and ovarian cancer susceptibility genes BRCA1 and BRCA2, and to estimate the future risks of developing breast or ovarian cancer. In this paper, we describe updates to the BOADICEA model that extend its capabilities, make it easier to use in a clinical setting and yield more accurate predictions.
METHODS: We describe: (1) updates to the statistical model to include cancer incidences from multiple populations; (2) updates to the distributions of tumour pathology characteristics using new data on BRCA1 and BRCA2 mutation carriers and women with breast cancer from the general population; (3) improvements to the computational efficiency of the algorithm so that risk calculations now run substantially faster; and (4) updates to the model's web interface to accommodate these new features and to make it easier to use in a clinical setting.
RESULTS: We present results derived using the updated model, and demonstrate that the changes have a significant impact on risk predictions.
CONCLUSION: All updates have been implemented in a new version of the BOADICEA web interface that is now available for general use:

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Bouchardy C, Rapiti E, Fioretta G, et al.
Impact of family history of breast cancer on tumour characteristics, treatment, risk of second cancer and survival among men with breast cancer.
Swiss Med Wkly. 2013; 143:w13879 [PubMed] Related Publications
BACKGROUND: Male breast cancer patients have a higher risk of developing a second primary cancer, but whether this risk differs according to the family history of breast or ovarian cancers remains to be elucidated. We aimed to determine the effect of a positive family history among men diagnosed with breast cancer on tumour characteristics, treatment, second cancer occurrence and overall survival.
METHODS: We included 46 patients with known information on the family history of breast or ovarian cancer recorded at the Geneva Cancer Registry between 1970 and 2009. We compared patients with and without a family history with chi-square of heterogeneity, risk of second cancer with standardised incidence ratios (SIRs), and overall survival by Kaplan-Meier methods.
RESULTS: Approximately 20% of men with breast cancer had a positive family history. No differences were observed between men with and without familial risk except that patients with increased risk were more likely to receive radiotherapy and hormone therapy when compared with patients without familial risk. This more complete therapy is likely to be explained by the heightened awareness of cancer treatment among breast cancer patients with affected family members. Six men developed a second cancer. SIRs for second cancer were not significantly increased among patients with or without familial risk (1.93, 95% confidence interval [CI] 0.23-6.97 and 1.04, 95% CI 0.28-2.66, respectively). Overall survival was not significantly different between the two groups.
CONCLUSIONS: Prognosis was similar among patients with or without familial risk. Our results are however based on small numbers and larger registry-based cohorts of males with precise data on familial risk are still warranted.

Related: Breast Cancer Ovarian Cancer

Rafique A, Arshad A
Myofibroblastoma: an unusual rapidly growing benign tumour in a male breast.
J Coll Physicians Surg Pak. 2013; 23(10):818-9 [PubMed] Related Publications
Myofibroblastoma is an unusual benign tumour of the breast predominantly seen in men in their sixth to seventh decade. The gross appearance is that of a well circumscribed nodule, characteristically small, seldom exceeding 3 cm. We present a case of an unusually large myofibroblastoma, which mimicked a malignant breast tumour. A 40 years old male, known case of tetralogy of Fallot, was operated in infancy in abroad, presented with a rapid enlargement of right breast over 5 - 6 weeks. Examination revealed a firm 10 cm hemispherical lump occupying the whole of the right breast with normal overlying skin. Since core biopsy was inconclusive, a subcutaneous mastectomy was performed to remove the tumour, which weighed 500 gms. Histopathology and immunocytochemistry revealed a mixed classical and collagenised type of myofibroblastoma. The patient is well with no evidence of recurrence.

Rizzolo P, Silvestri V, Tommasi S, et al.
Male breast cancer: genetics, epigenetics, and ethical aspects.
Ann Oncol. 2013; 24 Suppl 8:viii75-viii82 [PubMed] Related Publications
BACKGROUND AND STUDY DESIGN: Male breast cancer (MBC) is a rare disease compared with female BC and our current understanding regarding breast carcinogenesis in men has been largely extrapolated from the female counterpart. We focus on differences between the ethical issues related to male and female BC patients. A systematic literature search by using PubMed (, was carried out to provide a synopsis of the current research in the field of MBC genetics, epigenetics and ethics. Original articles and reviews published up to September 2012 were selected by using the following search key words to query the PubMed website: 'male breast cancer', 'male breast cancer and genetic susceptibility', 'male breast cancer and epigenetics', 'male breast cancer and methylation', 'male breast cancer and miRNA', 'male breast cancer and ethics'.
RESULTS AND CONCLUSIONS: As in women, three classes of breast cancer genetic susceptibility (high, moderate, and low penetrance) are recognized in men. However, genes involved and their impact do not exactly overlap in female and male BC. Epigenetic alterations are currently scarcely investigated in MBC, however, the different methylation and miRNA expression profiles identified to date in female and male BCs suggest a potential role for epigenetic alterations as diagnostic biomarkers. Overall, much still needs to be learned about MBC and, because of its rarity, the main effort is to develop large consortia for moving forward in understanding MBC and improving the management of MBC patients on a perspective of gender medicine.

Fields EC, DeWitt P, Fisher CM, Rabinovitch R
Management of male breast cancer in the United States: a surveillance, epidemiology and end results analysis.
Int J Radiat Oncol Biol Phys. 2013; 87(4):747-52 [PubMed] Related Publications
PURPOSE: To analyze the stage-specific management of male breast cancer (MBC) with surgery and radiation therapy (RT) and relate them to outcomes and to female breast cancer (FBC).
METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was queried for all primary invasive MBC and FBC diagnosed from 1973 to 2008. Analyzable data included age, race, registry, grade, stage, estrogen and progesterone receptor status, type of surgery, and use of RT. Stage was defined as localized (LocD): confined to the breast; regional (RegD): involving skin, chest wall, and/or regional lymph nodes; and distant: M1. The primary endpoint was cause-specific survival (CSS).
RESULTS: A total of 4276 cases of MBC and 718,587 cases of FBC were identified. Male breast cancer constituted 0.6% of all breast cancer. Comparing MBC with FBC, mastectomy (M) was used in 87.4% versus 38.3%, and breast-conserving surgery in 12.6% versus 52.6% (P<10(-4)). For males with LocD, CSS was not significantly different for the 4.6% treated with lumpectomy/RT versus the 70% treated with M alone (hazard ratio [HR] 1.33; 95% confidence interval [CI] 0.49-3.61; P=.57). Postmastectomy RT was delivered in 33% of males with RegD and was not associated with an improvement in CSS (HR 1.11; 95% CI 0.88-1.41; P=.37). There was a significant increase in the use of postmastectomy RT in MBC over time: 24.3%, 27.2%, and 36.8% for 1973-1987, 1988-1997, and 1998-2008, respectively (P<.0001). Cause-specific survival for MBC has improved: the largest significant change was identified for men diagnosed in 1998-2008 compared with 1973-1987 (HR 0.73; 95% CI 0.60-0.88; P=.0004).
CONCLUSIONS: Surgical management of MBC is dramatically different than for FBC. The majority of males with LocD receive M despite equivalent CSS with lumpectomy/RT. Postmastectomy RT is greatly underutilized in MBC with RegD, although a CSS benefit was not demonstrated. Outcomes for MBC are improving, attributable to improved therapy and its use in this unscreened population.

Related: Breast Cancer USA

De Sanctis V, Fiscina B, Soliman A, et al.
Klinefelter syndrome and cancer: from childhood to adulthood.
Pediatr Endocrinol Rev. 2013; 11(1):44-50 [PubMed] Related Publications
The classic clinical manifestations of Klinefelter syndrome (KS) are expressions of the primary hypogonadism that causes severe alterations of the reproductive and endocrine functions of the testis. It is a syndrome that causes infertility, and in addition leads to multiple disorders that involve a variety of tissues and organs. Important medical conditions associated with KS are categorized as: 1) motor, cognitive, and behavioral dysfunction; 2) tumors; 3) vascular disease and 4) endocrine/ metabolic and autoimmune diseases. The overall incidence of cancer in men with this syndrome is similar to that of the general population, but some malignancies show a significantly higher prevalence in these patients. It is possible that the increased risk of developing certain cancers can be attributed to a direct effect of the chromosomal abnormality (the supernumerary X chromosome), or the combined action of the abnormal chromosomes and hormonal imbalances. Although data in the literature on cancer and KS are abundant, most of them are individual case reports. Only three epidemiological studies with relatively large cohorts provide data with greater reliability, although each has inherent imitations related to study design. This review paper summarizes the current knowledge about cancer risk from childhood to adulthood in patients with KS.

Related: Haematological Malignancies & Realted Disorders Germ Cell Tumors Germ Cell Tumours in Children and Young Adults Germ Cell Tumors (Pediatric)

Moten A, Obirieze A, Wilson LL
Characterizing lobular carcinoma of the male breast using the SEER database.
J Surg Res. 2013; 185(2):e71-6 [PubMed] Related Publications
BACKGROUND: Lobular carcinoma of the male breast is rare. We sought to investigate the clinical characteristics, treatment, and outcomes of men and women with lobular breast cancer, using a population-based database.
METHODS: We reviewed the Surveillance, Epidemiology, and End Results database 1988-2008 and identified patients with a lobular breast cancer diagnosis (invasive lobular carcinoma [ILC] and lobular carcinoma in situ [LCIS]) using the "International Classification of Diseases for Oncology, Third Edition" codes. Bivariate analyses compared the male and female patients on demographics, clinical characteristics, and treatment modalities. Multivariate logistic regression analysis determined the risk-adjusted likelihood of receiving treatment. Survival analysis was done and hazard ratios were obtained using Cox proportional models.
RESULTS: Overall, 133,339 patients were identified, including 133,168 women (99.9%) and 171 men (0.1%). Most had ILC (82.08%). The median age was 66 ± 20 y for the men and 61 ± 21 y for the women. The men with ILC were more likely to have poorly differentiated tumors (26.45% versus 15.61%; P < 0.001) and stage IV disease (9.03% versus 4.18%; P = 0.005) than were the women. The cancer-specific 5-year survival rates for ILC were 82.9% for the men and 91.9% for the women. Adjusted survival was better for patients with ILC receiving surgery plus radiotherapy than patients receiving neither (hazard ratio 0.52, 95% confidence interval 0.49-0.56). Women with ILC had a 55% increased odds of receiving surgery plus radiotherapy compared with men (odds ratio 1.55, 95% confidence interval 1.08-2.22).
CONCLUSIONS: ILC presents at a higher grade and stage in men. The difference in disease characteristics and survival rates suggests that the treatment of men with lobular breast cancer should be adjusted to improve their outcomes.

Rugo HS, Brufsky AM, Ulcickas Yood M, et al.
Racial disparities in treatment patterns and clinical outcomes in patients with HER2-positive metastatic breast cancer.
Breast Cancer Res Treat. 2013; 141(3):461-70 [PubMed] Article available free on PMC after 21/01/2015 Related Publications
Data characterizing demographics, treatment patterns, and clinical outcomes in black patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) are limited. registHER is a large, observational cohort study of patients (n = 1,001) with HER2-positive MBC diagnosed ≤6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up of 27 months). Demographics, treatment patterns, and clinical outcomes were described for black (n = 126) and white patients (n = 793). Progression-free survival (PFS) following first-line therapy and overall survival (OS) were examined. Multivariate analyses adjusted for baseline and treatment factors. Black patients were more likely than white patients to be obese (body mass index ≥30), to have diabetes, and to have a history of cardiovascular disease; they were also less likely to have estrogen receptor or progesterone receptor positive disease. In patients treated with trastuzumab, the incidence of cardiac safety events (grade ≥3) was higher in black patients (10.9 %) than in white patients (7.9 %). Unadjusted median OS and PFS (months) were significantly lower in black patients than in white patients (OS: black: 27.1, 95 % confidence interval [CI] 21.3-32.1; white: 37.3, 95 % CI 34.6-41.1; PFS: black: 7.0, 95 % CI 5.7-8.2; white: 10.2, 95 % CI 9.3-11.2). The adjusted OS hazard ratio (HR) for black patients compared with white patients was 1.29 (95 % CI 1.00-1.65); adjusted PFS HR was 1.29 (95 % CI 1.05-1.59). This real-world evaluation of a large cohort of patients with HER2-positive MBC shows poorer prognostic factors and independently worse clinical outcomes in black versus white patients. Further research is needed to identify potential biologic differences that could have predictive impact for black patients or that could explain these differences.

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Limaiem F, Bouslama S, Haddad I, et al.
Hydatid cyst presenting as a breast lump in a male patient.
Pathologica. 2013; 105(3):101-3 [PubMed] Related Publications
The breast is a rare primary site of hydatid disease and accounts for only 0.27% of cases. Mammary hydatidosis generally occurs in females and has never been described in male patients. In this paper, the authors report a new case of isolated hydatid cyst of the breast in a 35-year-old previously healthy man, who presented with a left breast painless lump of one year duration. Physical examination showed a non-tender and immobile mass in the upper lateral quadrant of the left breast, with normal overlying skin and nipple. There was no palpable lymph node in the left axilla and the contralateral breast was normal. Ultrasonography showed a 2.7 x 1.5 cm cystic lesion in the left breast. The patient underwent total excision of the mass, and histopathological examination confirmed the diagnosis of hydatid cyst. The authors conclude that although hydatid cyst of the breast is rare, it should be considered in the differential diagnosis of breast lumps especially in endemic areas.

Serra R, Buffone G, Perri P, et al.
Male breast cancer manifesting as cephalic vein thrombosis.
Ann Vasc Surg. 2013; 27(8):1188.e9-11 [PubMed] Related Publications
Male breast cancer is an uncommon disease with a low annual prevalence in Western countries. Venous thromboembolism may be associated during malignancy of the breast. We report a 70-year-old man who presented with superficial vein thrombosis of right upper limb that predicted the diagnosis of breast invasive ductal carcinoma. Key issues surrounding the diagnosis, treatment, and relationship between breast cancer and venous disorders are discussed. Breast cancer and venous thromboembolism are 2 conditions that are often correlated more than expected, and attention to the combination of these clinical presentations is required.

Di Lauro L, Vici P, Del Medico P, et al.
Letrozole combined with gonadotropin-releasing hormone analog for metastatic male breast cancer.
Breast Cancer Res Treat. 2013; 141(1):119-23 [PubMed] Related Publications
The role of aromatase inhibitors combined with gonadotropin-releasing hormone analog in metastatic male breast cancer patients remains unknown. In this retrospective study we evaluated the activity of letrozole combined with a gonadotropin-releasing hormone analog as a first- or second-line therapy for metastatic male breast cancer patients. 19 men entered the study. We did not observe any grade 3 or 4 adverse events. 2 patients (10.5 %) had complete response, 7 patients (36.8 %) experienced a partial response, 7 patients (36.8 %) had stable disease lasting ≥ 6 months, and 3 patients (15.8 %) had progressive disease. Overall, the disease control rate was 84.2 %. Median progression-free survival was 12.5 months (95 % CI 8.2-16.9), median overall survival was 35.8 months (95 % CI 24.4-49.2), 1- and 2-year survival rates were 89.5 and 67 %, respectively. Interestingly, 3 out of 4 patients treated with the combination following disease progression while on aromatase inhibitor monotherapy confirmed or improved the best overall response observed in the first-line setting. The combination of letrozole and gonadotropin-releasing hormone analog is effective and safe in hormone-receptor positive, metastatic male breast cancer patients.

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Madhukar M, Chetlen A
Multimodality imaging of benign and malignant male breast disease.
Clin Radiol. 2013; 68(12):e698-706 [PubMed] Related Publications
With the increasing use of advanced imaging techniques, male breast lesions are being visualized using techniques other than mammography and ultrasound. This review illustrates benign and malignant male breast disease on both conventional imaging as well as advanced imaging methods including computed tomography, magnetic resonance imaging, and positron-emission tomography in order to familiarize the radiologist with typical imaging appearances and review the proper clinical management.

Stoodley PW, Richards DA, Boyd A, et al.
Left ventricular systolic function in HER2/neu negative breast cancer patients treated with anthracycline chemotherapy: a comparative analysis of left ventricular ejection fraction and myocardial strain imaging over 12 months.
Eur J Cancer. 2013; 49(16):3396-403 [PubMed] Related Publications
AIM: Anthracycline agents are undermined by their cardiotoxicity. As life expectancy following treatment is greatly improved, techniques that ensure early detection and timely management of cardiotoxicity are essential. The aim of the present study was to evaluate left ventricular (LV) systolic function with LV ejection fraction (LVEF) and two-dimensional myocardial strain up to 12 months after anthracycline chemotherapy, specifically in HER2/neu negative breast cancer patients.
METHODS: Seventy-eight consecutive anthracycline naïve breast cancer patients were studied before and immediately after anthracycline chemotherapy. Fifty HER2/neu negative patients were studied over 12 months with serial echocardiograms at four time points. All patients were treated with standard regimens containing anthracyclines.
RESULTS: Global systolic strain was significantly reduced immediately after, and 6 months after anthracyclines (-19.0 ± 2.3% to -17.5 ± 2.3% (P<0.001) and -18.2 ± 2.2% (P=0.01) respectively). A non-uniform reduction in strain was observed each time with relative sparing of the LV apex. LVEF remained largely unchanged at both time points. Global strain normalised by 12 months in the majority of patients. Persistently reduced strain was observed in 16% (n=8); these patients had a greater reduction in strain at 6 months (≤ -17.2%), and had received higher cumulative anthracycline doses.
CONCLUSION: Myocardial strain imaging is more sensitive than LVEF for the early detection and intermediate term monitoring of LV systolic function following anthracycline chemotherapy in HER2/neu negative breast cancer patients, and may aid in the development of improved monitoring protocols.

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Chen X, Liu X, Zhang L, et al.
Poorer survival of male breast cancer compared with female breast cancer patients may be due to biological differences.
Jpn J Clin Oncol. 2013; 43(10):954-63 [PubMed] Related Publications
OBJECTIVE: The objective of the study was to compare disease-free survival and overall survival in a group of matched males and females with breast cancer, and to analyze possible treatment- and gender-related differences.
METHODS: We retrospectively analyzed the data of 150 operable male breast cancer patients treated in our hospital from December 1980 to June 2012. Each male breast cancer patient recorded in the database was matched with two female breast cancer patients of equal stage. Prognosis in terms of disease-free survival and overall survival was evaluated.
RESULTS: The mean age at diagnosis was 58.6 ± 9.7 years for males and 57.2 ± 10.3 years for females. The median follow-up was 69 months for males and 81 months for females. Significant differences were identified for tumor location, hormone receptor status, molecular subtypes and hormone therapy between the two groups. Monofactorial analysis demonstrated that tumor size, lymph node state, American Joint Committee on Cancer stage, molecular subtypes and adjuvant chemotherapy treatment were prognostic factors in male breast cancer patients. The 5- and 10-year disease-free survival rates were 65.6 and 40.1% for males, and 74.9 and 51.5% for females, respectively. The 5- and 10-year overall survival rates were 72.9 and 53.9% for males, and 83.2 and 68.5% for females, respectively. There was significantly difference in disease-free survival and overall survival between the two matched groups (P = 0.002).
CONCLUSIONS: Male breast cancer patients had inferior outcome despite of equal stage in comparison with matched female breast cancer patients, which demonstrates that biological differences may contribute to the worse prognosis.

Related: Breast Cancer

Teffera T, Yerakle F, Schneider J
Young male patient with advanced breast cancer: a case report.
Ethiop Med J. 2012; 50(4):375-7 [PubMed] Related Publications
Breast cancer in male is a rare disease, accounting for less than 1% all breast cancer cases. The incidence of male breast carcinoma increases with advancing patient age. This is the case report of a young man with a breast mass, which turned out to be malignant.

Ni YB, Mujtaba S, Shao MM, et al.
Columnar cell-like changes in the male breast.
J Clin Pathol. 2014; 67(1):45-8 [PubMed] Related Publications
AIMS: Columnar cell lesions are known as a link between normal breast and low grade neoplastic lesions in female, but have not been established in the male breast. This study evaluated the presence of ducts showing columnar cell-like features in the male breast.
METHODS: Seventy-one consecutive surgical resections from men (6 invasive breast carcinoma of grade 3, 1 atypical ductal hyperplasia and 64 other lesions) were reviewed to identify foci of dilated ducts with columnar epithelial cells, and their morphological features including apical snouts, intraluminal secretions and calcifications were assessed. The expression of CK5/6 and estrogen receptor (ER) was evaluated immunohistochemically. Clinicopathological features including patients' age, histological diagnosis and gynaecomastoid hyperplasia were documented.
RESULTS: Ducts showing columnar cell-like features were identified in 39 cases, morphologically as distended ducts with round or undulating outline. There was an outer layer of myoepithelial cells and an inner layer of columnar luminal cells showing apical snouts, but without intraluminal secretions or calcifications. Immunohistochemically, these columnar epithelial cells were negative for CK5/6 in 38/39 cases and all were ER heterogeneously positive. These changes were associated with older age, but their incidence did not differ whether they were associated with invasive breast carcinoma, atypical ductal hyperplasia and other lesions.
CONCLUSIONS: In the male breast, there is an entity sharing morphological features and immunohistochemical profile of columnar cell lesions.

Fogh S, Kachnic LA, Goldberg SI, et al.
Localized therapy for male breast cancer: functional advantages with comparable outcomes using breast conservation.
Clin Breast Cancer. 2013; 13(5):344-9 [PubMed] Related Publications
BACKGROUND: Male breast cancer (MBC) accounts for approximately 1% of all breast cancers. Given the rarity of this disease, treatment of MBC generally follows the same principles as treatment of female breast cancer. However, the traditional surgical approach for MBC is modified radical mastectomy (MRM) or total simple mastectomy (TSM) instead of breast conservation surgery (BCS). The purpose of this study was to examine the feasibility of BCS as an alternative to mastectomy for MBC with respect to musculoskeletal functionality and treatment outcome.
PATIENTS AND METHODS: A retrospective analysis was undertaken of all male patients with breast cancer who presented to Massachusetts General Hospital or Boston Medical Center for localized therapy from 1990 to 2003. Musculoskeletal functionality (tissue fibrosis, arm edema, and range of motion) and treatment outcome (local-regional control, disease-free survival, and overall survival) were evaluated. Functional/cosmetic outcomes were assessed by multidisciplinary review of patient follow-up visits and were scored as either "good-excellent" or "fair-poor" to account for subjectivity between different clinicians.
RESULTS: Forty-two patients in total were identified to undergo localized treatment. Thirty patients (71%) received MRM, 4 (10%) had TSM, and 8 (19%) underwent BCS. Actuarial overall 1-year fair-poor documented tissue fibrosis, arm edema, and decreased range of motion rates were 13%, 23%, and 27% for patients receiving MRM; 25%, 0%, and 50% for patients who underwent TSM; and 13%, 0%, and 0% for those undergoing BCS, respectively. Overall survival and disease-free survival were not statistically different between the groups.
CONCLUSIONS: These data suggest that breast conservation therapy may be considered a reasonable local treatment option for male patients presenting with breast cancer because it may offer functional advantages over mastectomy with comparable rates of local control and disease-free survival and overall survival.

Related: Breast Cancer

Patten DK, Sharifi LK, Fazel M
New approaches in the management of male breast cancer.
Clin Breast Cancer. 2013; 13(5):309-14 [PubMed] Related Publications
Male breast cancer (MBC) is a rare condition that accounts for 0.1% of all male cancers. Our current evidence base for treatment is derived from female breast cancer (FBC) patients. Risk factors for MBC include age, genetic predisposition, race, sex hormone exposure, and environmental factors. Most patients present later and with more advanced disease than comparable FBC patients. Tumors are likely to be estrogen receptor and progesterone receptor positive, with the most common histologic type being invasive ductal carcinoma. Triple assessment remains the criterion standard for diagnosis. Primary MBC is mostly managed initially by simple mastectomy, with the option of breast conserving surgery, which carries an increased risk of recurrence. Sentinel node biopsy is recommended as the initial procedure for staging the axilla. Reconstructive surgery focuses on achieving primary skin closure, and radiotherapy largely follows treatment protocols validated in FBC. We recommend chemotherapy for men with more advanced disease, in particular, those with estrogen receptor negative histology. MBC responds well to endocrine therapy, although it is associated with significant adverse effects. Third-generation aromatase inhibitors are promising but raise concerns due to their failure to prevent estrogen synthesis in the testes. Fulvestrant remains unproven as a therapy, and data on trastuzumab is equivocal with HER2 receptor expression and functionality unclear in MBC. In metastatic disease, drug-based hormonal manipulation remains a first-line therapy, followed by systemic chemotherapy for hormone-refractory disease. Prognosis for MBC has improved over the past 30 years, with survival affected by disease staging, histologic classification, and comorbidity.

Related: Monoclonal Antibodies

Ishida M, Mori T, Umeda T, et al.
Pleomorphic lobular carcinoma in a male breast: a case report with review of the literature.
Int J Clin Exp Pathol. 2013; 6(7):1441-4 [PubMed] Article available free on PMC after 21/01/2015 Related Publications
Invasive lobular carcinoma (ILC) is a distinct type of breast carcinoma and represents 5-15% of invasive breast carcinomas in female. However, the occurrence of ILC is exceptional in male breast, and the incidence is 1.5-1.9% of male breast carcinomas. Herein, we report a case of pleomorphic lobular carcinoma in a male breast. A 76-year-old Japanese male with a history of treatment with a progestational agent for prostate cancer presented with a right breast tumor. Magnetic resonance imaging showed gynecomastia of bilateral breasts and an irregular-shaped nodule in his right breast. Histopathological study revealed infiltrative neoplastic growth of discohesive tumor cells arranged in single-filed linear cords or trabeculae. These neoplastic cells had variable-sized large nuclei containing occasional nucleoli. Immunohistochemically, these tumor cells lacked E-cadherin expression. Accordingly, an ultimate diagnosis of pleomorphic lobular carcinoma was made. This is the third documented case of pleomorphic lobular carcinoma of male breast. Our analyses of the clinicopathological features of this type of tumor revealed that patients were middle-aged or elderly men, and all cases were free from lymph node metastases or recurrence. Gynecomastia and a history of hormonal agent intake were present only in the current case. The most commonly proposed risk factor for the development of male breast cancer is elevated level of estrogen, and a possible link between the development of male breast cancer and estrogen therapy for prostate cancer has been suggested. The clinicopathological features of ILC of male breast remains unclear; therefore, additional studies are needed to clarify them.

Related: Prostate Cancer

Tan TJ, Leong LC, Sim LS, Sim LS
Clinics in diagnostic imaging (147). Male breast carcinoma.
Singapore Med J. 2013; 54(6):347-52 [PubMed] Related Publications
A 51-year-old man with no significant medical history was referred to our institution for further management of a palpable, painless right breast lump that had been gradually increasing in size for a period of six months. Physical examination revealed a firm right breast lump and bloody right nipple discharge, but no skin involvement or axillary lymphadenopathy was observed. Subsequent mammography and breast ultrasonography demonstrated a discrete, heterogeneous and vascular right breast mass with spiculated and angulated margins. The breast mass was found to be an invasive ductal carcinoma on ultrasonography-guided core needle biopsy. This case illustrates that a combination of detailed clinical history, careful physical examination and radiological assessment using mammography and breast ultrasonography may be used to identify cases suspicious for male breast carcinoma that warrant biopsy.

Rashid MU, Muhammad N, Faisal S, et al.
Constitutional CHEK2 mutations are infrequent in early-onset and familial breast/ovarian cancer patients from Pakistan.
BMC Cancer. 2013; 13:312 [PubMed] Article available free on PMC after 21/01/2015 Related Publications
BACKGROUND: Less than 20% of Pakistani women with early-onset or familial breast/ovarian cancer harbor germ line mutations in the high-penetrance genes BRCA1, BRCA2 and TP53. Thus, mutations in other genes confer genetic susceptibility to breast cancer, of which CHEK2 is a plausible candidate. CHEK2 encodes a checkpoint kinase, involved in response to DNA damage.
METHODS: In the present study we assessed the prevalence of CHEK2 germ line mutations in 145 BRCA1/2-negative early-onset and familial breast/ovarian cancer patients from Pakistan (Group 1). Mutation analysis of the complete CHEK2 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments.
RESULTS: Two potentially deleterious missense mutations, c.275C>G (p.P92R) and c.1216C>T, (p.R406C), were identified (1.4%). The c.275C>G mutation is novel and has not been described in other populations. It was detected in a 30-year-old breast cancer patient with a family history of breast and multiple other cancers. The c.1216C>T mutation was found in a 34-year-old ovarian cancer patient from a family with two breast cancer cases. Both mutations were not detected in 229 recently recruited BRCA1/2-negative high risk patients (Group 2).
CONCLUSION: Our findings suggest that CHEK2 mutations may not contribute significantly to breast/ovarian cancer risk in Pakistani women.

Related: Breast Cancer Ovarian Cancer

Kryvenko ON, Chitale DA, Yoon J, et al.
Precursor lesions of mucinous carcinoma of the breast: analysis of 130 cases.
Am J Surg Pathol. 2013; 37(7):1076-84 [PubMed] Related Publications
Mucinous mammary carcinoma (MC) is a tumor type with relatively favorable prognosis. Unlike the circumstances surrounding conventional invasive duct carcinoma, data are limited regarding precursor lesions for MC. This study characterizes patterns of mucinous ductal carcinoma in situ (DCIS) as a precursor lesion for MC. All slides from 130 cases of MC encountered between 2000 and 2011 at Henry Ford Hospital, Detroit, MI were reviewed to subclassify MC, identify DCIS, and explore transition patterns from DCIS to MC. Calponin, p63, chromogranin, synaptophysin, CD56, and MIB-1 immunostaining analyses were performed in 65 cases. Among 106 cases of pure (71 type A, 35 type B) and 24 cases of mixed MC, DCIS appeared in 88 (68%) specimens, with all but 4 showing luminal mucin accumulation. Dominant patterns of mucinous DCIS were cribriform/solid (66), cribriform and papillary (7), papillary (5), micropapillary (3), and flat (3). Fifty-seven (68%) cases of mucinous DCIS demonstrated transitions from DCIS to MC. Luminal mucinous distention, focal flattening and attenuation of the epithelium, and disruption of the duct wall resulting in a mucocele-like extravasation of malignant epithelia with escaping mucin was a transition pattern seen with all architectures of DCIS and in all types of MC. This was the only pattern of transition to type A MC. The epithelial outpouching, formation of a cleft with accumulation of mucin around the epithelium, and transition into mucin pools with floating tumor cell clusters was the second transition pattern that went from cribriform/solid DCIS to type B and mixed MC. DCIS preceding aggressive phenotypes of MC (type B and mixed) more often had a cribriform/solid architecture, higher nuclear grade, and higher Ki-67-labeling index (all P<0.05). In summary, mucinous DCIS is a precursor to MC with distinctive features that link patterns of DCIS with aggressive MC phenotypes. The 2 observed transitions between mucinous DCIS and MC suggest that pathogenesis of different types of MC is different correlating with less or more aggressive behavior of the latter.

Related: MKI67

Lacle MM, Kornegoor R, Moelans CB, et al.
Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification.
Mod Pathol. 2013; 26(11):1461-7 [PubMed] Related Publications
Gene copy number changes have an important role in carcinogenesis and could serve as potential biomarkers for prognosis and targets for therapy. Copy number changes mapping to chromosome 16 have been reported to be the most frequent alteration observed in female breast cancer and a loss on 16q has been shown to be associated with low grade and better prognosis. In the present study, we aimed to characterize copy number changes on 16q in a group of 135 male breast cancers using a novel multiplex ligation-dependent probe amplification kit. One hundred and twelve out of 135 (83%) male breast cancer showed copy number changes of at least one gene on chromosome 16, with frequent loss of 16q (71/135; 53%), either partial (66/135; 49%) or whole arm loss (5/135; 4%). Losses on 16q were thereby less often seen in male breast cancer than previously described in female breast cancer. Loss on 16q was significantly correlated with favorable clinicopathological features such as negative lymph node status, small tumor size, and low grade. Copy number gain of almost all genes on the short arm was also significantly correlated with lymph node negative status. A combination of 16q loss and 16p gain correlated even stronger with negative lymph node status (n=112; P=0.012), which was also underlined by unsupervised clustering. In conclusion, copy number loss on 16q is less frequent in male breast cancer than in female breast cancer, providing further evidence that male breast cancer and female breast cancer are genetically different. Gain on 16p and loss of 16q identify a group of male breast cancer with low propensity to develop lymph node metastases.

Related: Chromosome 16

Zagouri F, Sergentanis TN, Koutoulidis V, et al.
Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series.
Br J Cancer. 2013; 108(11):2259-63 [PubMed] Article available free on PMC after 21/01/2015 Related Publications
BACKGROUND: Data regarding the safety and effectiveness of aromatase inhibitors (AIs) as monotherapy or combined with gonadotropin-releasing hormone (GnRH) analogue in male breast cancer are scarce.
METHODS: In this retrospective chart review, cases of male breast cancer patients treated with AIs with or without a GnRH analogue were evaluated.
RESULTS: Twenty-three men were included into this case series. Aromatase inhibitors in combination with or without a GnRH analogue were given as first-line therapy in 60.9% and as second-line therapy in 39.1% of patients, respectively. All patients had visceral metastases, whereas in five of them bone lesions coexisted. In all cases AIs were tolerated well, and no case of grade 3 and 4 adverse events was reported. A partial response was observed in 26.1% of patients and stable disease in 56.5%. Median overall survival (OS) was 39 months and median progression-free survival (PFS) was 13 months. Regarding OS and PFS, no significant effects of GnRH analogue co-administration or type of AI were noted.
CONCLUSION: Our study shows that AIs with or without GnRH analogues may represent an effective and safe treatment option for hormone-receptor positive, pretreated, metastatic, male breast cancer patients.

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