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).

Sas-Korczynska B, Niemiec J, Harazin-Lechowska A, et al.
The biological markers and results of treatment in male breast cancer patients. The Cracow experience.
Neoplasma. 2014; 61(3):331-9 [PubMed] Related Publications
Male breast cancer is a rare form of carcinoma with an incidence rate of approximately 0.5-1% compared with cases of breast carcinoma as a whole. Male breast cancer reacts effectively to endocrine therapy because of a high frequency of hormone receptor expression.The aim of the present study was the assessment of correlations between stage, grade, expression of steroid receptors, basal/mesenchymal markers and proliferation index, as well as analysis of the impact of the above-mentioned parameters on overall (OS) and disease-free survival (DFS) in the group of 32 male breast cancer patients, treated at the Centre of Oncology in Cracow.We showed the significant positive correlation between MIB-1 LI and tumor stage, and hormone receptors (ER or PgR) immunonegativity, and expression of EGFR, vimentin (p<0.05) and P-cadherin (the last at statistical border). The presence of any of basal or masenchymal markers correlated with a more advanced tumor stage. Moreover tumors without vimentin expression were characterised by lower MIB-1 LI and were more frequently EGFR immunonegative.We found that hormone receptor negativity, vimentin immunopositivity and high MIB-1 LI are significant independent indicators of poor OS and DFS for male breast cancer patients (p<0.05).

Related: MKI67

Corbex M, Bouzbid S, Boffetta P
Features of breast cancer in developing countries, examples from North-Africa.
Eur J Cancer. 2014; 50(10):1808-18 [PubMed] Related Publications
Epidemiological features of breast cancer appear to be different in developing countries compared to Western countries, with notably large proportions of young patients, male patients and aggressive forms of the disease. Using North-Africa (Morocco, Algeria, Tunisia, Libya and Egypt) as an example, we document the magnitude and explore possible explanations for such patterns. Articles and reports published since the seventies were reviewed. Results show that breast cancer incidence in females is 2-4 times lower in North-Africa than in Western countries while incidence in males is similar. Consequently, the relative proportion of male breast cancer is high (≈2% of all breast cancers). Similarly, the incidence of aggressive forms of the disease, like inflammatory or triple negative breast cancer (in females), is not higher in North Africa than in Western countries, but their relative proportion in case series (up to 10% for inflammatory and 15-25% for triple negative) is significantly higher because of low incidence of other forms of the disease. In North Africa, the incidence among women aged 15-49 is lower than in Western countries, but the very low incidence among women aged more than 50, combined to the young age pyramid of North-Africa, makes the relative proportions of young patients substantially higher (50-60% versus 20% in France). Such epidemiological features result mainly from peculiar risk factor profiles, which are typical for many developing countries and include notably rapid changes in reproductive behaviours. These features have important implications for breast cancer control and treatment.

Related: Breast Cancer Breast Cancer Screening Cancer Screening and Early Detection

Till JE, Beck HL, Aanenson JW, et al.
Military participants at U.S. Atmospheric nuclear weapons testing--methodology for estimating dose and uncertainty.
Radiat Res. 2014; 181(5):471-84 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
Methods were developed to calculate individual estimates of exposure and dose with associated uncertainties for a sub-cohort (1,857) of 115,329 military veterans who participated in at least one of seven series of atmospheric nuclear weapons tests or the TRINITY shot carried out by the United States. The tests were conducted at the Pacific Proving Grounds and the Nevada Test Site. Dose estimates to specific organs will be used in an epidemiological study to investigate leukemia and male breast cancer. Previous doses had been estimated for the purpose of compensation and were generally high-sided to favor the veteran's claim for compensation in accordance with public law. Recent efforts by the U.S. Department of Defense (DOD) to digitize the historical records supporting the veterans' compensation assessments make it possible to calculate doses and associated uncertainties. Our approach builds upon available film badge dosimetry and other measurement data recorded at the time of the tests and incorporates detailed scenarios of exposure for each veteran based on personal, unit, and other available historical records. Film badge results were available for approximately 25% of the individuals, and these results assisted greatly in reconstructing doses to unbadged persons and in developing distributions of dose among military units. This article presents the methodology developed to estimate doses for selected cancer cases and a 1% random sample of the total cohort of veterans under study.

Related: USA

Yardley DA, Tripathy D, Brufsky AM, et al.
Long-term survivor characteristics in HER2-positive metastatic breast cancer from registHER.
Br J Cancer. 2014; 110(11):2756-64 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
BACKGROUND: Data characterising long-term survivors (LTS) with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) are limited. This analysis describes LTS using registHER observational study data.
METHODS: A latent class modelling (LCM) approach was used to identify distinct homogenous patient groups (or classes) based on progression-free survival (PFS), overall survival, and complete response. Demographics, clinicopathologic factors, first-line treatment patterns, and clinical outcomes were described for each class. Class-associated factors were evaluated using logistic regression analysis.
RESULTS: LCM identified two survivor groups labelled as LTS (n=244) and short-term survivors (STS; n=757). Baseline characteristics were similar between groups, although LTS were more likely to be white (83.6% vs 77.8%) with oestrogen receptor-positive (ER+) or progesterone receptor-positive (PgR+) disease (59.4% vs 50.9%). Median PFS in LTS was 37.2 (95% confidence interval (CI): 32.9-40.5) vs 7.3 months (95% CI: 6.8-8.0) in STS. Factors associated with long-term survival included ER+ or PgR+ disease, metastasis to node/local sites, first-line trastuzumab use, and first-line taxane use.
CONCLUSIONS: Prognostic variables identified by LCM define a HER2-positive MBC patient profile and therapies that may be associated with more favourable long-term outcomes, enabling treatment selection appropriate to the patient's disease characteristics.

Related: Breast Cancer

Brinton LA, Cook MB, McCormack V, et al.
Anthropometric and hormonal risk factors for male breast cancer: male breast cancer pooling project results.
J Natl Cancer Inst. 2014; 106(3):djt465 [PubMed] Article available free on PMC after 01/03/2015 Related Publications
BACKGROUND: The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors.
METHODS: In the Male Breast Cancer Pooling Project, a consortium of 11 case-control and 10 cohort investigations involving 2405 case patients (n = 1190 from case-control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design-specific (case-control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided.
RESULTS: Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86).
CONCLUSIONS: Consistent findings across case-control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.

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

Hotko YS
Male breast cancer: clinical presentation, diagnosis, treatment.
Exp Oncol. 2013; 35(4):303-10 [PubMed] Related Publications
Despite male breast cancer is rare in occurrence, it is a serious problem. In 2012, 130 men in Ukraine got breast cancer that constituted 0.74% from all patients with mentioned pathology detected in the course of year. Every year in Ukraine approximately 100 men die from breast cancer. Still many aspects of male breast cancer remain unstudied. It occurs since information about mentioned disease is mainly based on retrospective analysis of small groups. Treatment of men, who got breast cancer, is based on knowledge, which has been obtained in treatment of women with this pathology. This article is based on the results of analysis of 168 cases of breast cancer in men, who have been examined and treated in the period from 1956 to 2012. In paper the peculiarities of clinical manifestations of male breast cancer have been determined, the optimal volume of diagnostic procedures in men with suspicion of breast cancer has been established, the mammographic signs have been detected and the possible histological variants of disease have been determined, clinical course peculiarities of male breast cancer have been defined, the most essential factors of prognosis of the disease have been fixed. Furthermore, in article optimal volume of surgical treatment of male breast cancer has been substantiated, the role and place of radiotherapy in treatment of this pathology has been determined. It has been proved that adjuvant polychemotherapy should be applied to the patients with male breast cancer independently from stage of process. Also optimal schemes of this kind of treatment have been determined. The efficacy of hormonal therapy with antiestrogen in patients with positive receptors of steroid hormones and at presence of unfavorable prognostic factors of disease has been demonstrated. The inefficiency of orchiectomy as one of the widespread kinds of hormonal therapy of male breast cancer has been defined.

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.

Related: TP53

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:

Related: Breast Cancer

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.

Related: Breast Cancer Trastuzumab (Herceptin)

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.

Gooren LJ, van Trotsenburg MA, Giltay EJ, van Diest PJ
Breast cancer development in transsexual subjects receiving cross-sex hormone treatment.
J Sex Med. 2013; 10(12):3129-34 [PubMed] Related Publications
INTRODUCTION: Transsexual people receive cross-sex hormones as part of their treatment, potentially inducing hormone-sensitive malignancies.
AIM: To examine the occurrence of breast cancer in a large cohort of Dutch male and female transsexual persons, also evaluating whether the epidemiology accords with the natal sex or the new sex.
MAIN OUTCOME MEASURE: Number of people with breast cancer between 1975 and 2011.
METHODS: We researched the occurrence of breast cancer among transsexual persons 18-80 years with an exposure to cross-sex hormones between 5 to >30 years. Our study included 2,307 male-to-female (MtF) transsexual persons undergoing androgen deprivation and estrogen administration (52,370 person-years of exposure), and 795 female-to-male (FtM) subjects receiving testosterone (15,974 total years of exposure).
RESULTS: Among MtF individuals one case was encountered, as well as a probable but not proven second case. The estimated rate of 4.1 per 100,000 person-years (95% confidence interval [CI]: 0.8-13.0) was lower than expected if these two cases are regarded as female breast cancer, but within expectations if viewed as male breast cancer. In FtM subjects, who were younger and had shorter exposure to cross-sex hormones compared with the MtF group, one breast cancer case occurred. This translated into a rate of 5.9 per 100,000 person-years (95% CI: 0.5-27.4), again lower than expected for female breast cancer but within expected norms for male breast cancer.
CONCLUSIONS: The number of people studied and duration of hormone exposure are limited but it would appear that cross-sex hormone administration does not increase the risk of breast cancer development, in either MtF or FtM transsexual individuals. Breast carcinoma incidences in both groups are comparable to male breast cancers. Cross-sex hormone treatment of transsexual subjects does not seem to be associated with an increased risk of malignant breast development.

Related: Breast Cancer

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.

Related: Cyclophosphamide Epirubicin Fluorouracil Methotrexate Docetaxel

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.

Related: Breast Cancer

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

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