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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Latest Research Publications

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

Gao YG, Zhang SH, Wang Y
A case of accessory mammary cancer in a male patient and a literature review.
Eur J Gynaecol Oncol. 2014; 35(4):452-5 [PubMed] Related Publications
A 68-year-old Chinese male patient was referred to the present hospital because of a right axillary lump in May 2011. Physical examination showed a rigid movable mass measuring 35 mm in diameter in the right axilla. No mass was palpable in either breast. Mammograms were normal. Physical and imaging examination of the head and neck region, lung, and upper and lower gastrointestinal tract also revealed no evidence of a primary tumor. Ultrasonography and resonance imaging (MRI) revealed no evidence of tumors in the bilateral mammary glands. Fine needle histological biopsy for suspected malignancy was performed, and the patient underwent tumor resection with axillary lymph node dissection on Jun 2011. Moderately differentiated adenocarcinoma in ectopic breast tissue was diagnosed based on the pathologic result, the tumor was immunohistochemically positive for ER, PR, and HER-2.

Wenhui Z, Shuo L, Dabei T, et al.
Androgen receptor expression in male breast cancer predicts inferior outcome and poor response to tamoxifen treatment.
Eur J Endocrinol. 2014; 171(4):527-33 [PubMed] Related Publications
OBJECTIVE: Androgen receptor (AR) plays an important role in male breast cancer (MBC). Additionally, endocrine therapy is the most important treatment in oestrogen receptor (ER)-positive advanced breast cancer. This study was aimed to investigate the role of AR in MBC treatment and prognosis and to analyse the relationship between AR and the effect of tamoxifen treatment in MBC patients.
METHODS: AR protein levels and other tumour characteristics (e.g. expression of ER (ESR1), PR (PGR), AR, HER2 (ERBB2) and Ki-67 (MKI67)) in breast cancer tissue from 102 MBC patients were determined using immunohistochemical analysis. Additionally, the relationship between AR status and clinicopathological features was analysed using the χ(2)-test. Association with survival was initially analysed using the Kaplan-Meier method and the log-rank test, and Cox regression analysis was used to adjust for other prognostic indicators.
RESULTS: High expression of AR was not correlated with T-stage, histological grade, HER2 status and the status of other sex hormone receptors, but was associated with lymph node metastases (P=0.032). AR-positive patients showed significantly shorter 5-year overall survival (OS) rates (P=0.045) and 5-year disease-free survival (DFS) rates (P=0.026) than AR-negative patients. By contrast, for patients who received tamoxifen therapy, AR-negative patients showed a higher clinical benefit rate than AR-positive patients (P=0.025). Additionally, the median TTP and OS were significantly different (P=0.02 for TTP; P=0.029 for OS).
CONCLUSIONS: AR expression correlates strongly with both OS and DFS in patients with MBC. AR-positive patients can predict a poorer clinical outcome than AR-negative patients after adjuvant tamoxifen therapy.

Related: MKI67 AR: androgen receptor

Park YM, Wu Y, Wei W, Yang WT
Primary neuroendocrine carcinoma of the breast: clinical, imaging, and histologic features.
AJR Am J Roentgenol. 2014; 203(2):W221-30 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to evaluate the clinical, imaging, and histopathologic findings of primary neuroendocrine carcinoma of the breast.
MATERIALS AND METHODS: A pathology database was searched for the records of patients with a histopathologic diagnosis of primary neuroendocrine carcinoma of the breast who had undergone mammography, sonography, or MRI between 1984 and 2011. The imaging studies of eligible patients were retrospectively reviewed according to the BI-RADS lexicon, and clinical presentation and histopathologic characteristics were documented. Imaging characteristics were compared with historical controls of invasive mammary carcinoma.
RESULTS: Eighty-seven patients (84 women, three men; mean age, 62.9 years; range, 28-89 years) were included in the study. The mean tumor size was 3.1 cm (range, 0.6-11 cm). Sixty-five of 84 (77.4%) cancers were estrogen and progesterone receptor positive and ERBB2 negative. A palpable mass (55.8%) was a common clinical manifestation. A high-density, round or oval, or lobular mass with nonspiculated margins on mammograms and an irregular (65.4%), hypoechoic (78.4%) mass, with indistinct margins (43.5%), no or enhanced posterior acoustic features (77.9%) on sonograms were common findings. MRI revealed an irregular mass (83.3%), irregular margins (63.6%), and washout kinetics (85.7%). Neuroendocrine carcinoma presented more frequently as masses on mammograms. Calcifications were infrequent compared with their occurrence in invasive mammary cancer.
CONCLUSION: Primary neuroendocrine carcinoma of the breast has mammographic features that differ from those of invasive mammary carcinoma. A round, oval, or lobular mass with nonspiculated margins, positive estrogen and progesterone receptor results, and negative ERBB2 results should raise suspicion of primary neuroendocrine carcinoma.

Related: Breast Cancer

Grenader T, Yerushalmi R, Tokar M, et al.
The 21-gene recurrence score assay (Oncotype DX™) in estrogen receptor-positive male breast cancer: experience in an Israeli cohort.
Oncology. 2014; 87(1):1-6 [PubMed] Related Publications
OBJECTIVE: The 21-gene recurrence score (RS) assay has been widely adopted for use in early estrogen receptor (ER)-positive breast cancer to assess the risk for distant recurrence and the potential benefit of adjuvant chemotherapy. The primary aim of this study was to assess RS distribution in Israeli male breast cancer (MBC) patients.
METHODS: The study population included 65 newly diagnosed Israeli MBC patients. Clinical and pathologic data were collected at the time of referral. Pathologic examinations were conducted at the pathology departments of the referring centers. The RS assay (Oncotype DX™) was performed on paraffin-embedded tumor samples at Genomic Health laboratories.
RESULTS: The mean age of the patients was 65.1 years (range 38-88 years). Low-risk (RS<18), intermediate-risk (RS 18-30) and high-risk (RS≥31) scores were noted in 29 patients (44.6%), 27 patients (41.5%) and 9 patients (13.9%), respectively. The distribution of RS in male patients was similar to the distribution in 2,455 female patients from Israel referred during the same time period.
CONCLUSION: Our data suggest that the distribution of Oncotype DX RS in ER-positive MBC patients is similar to that of female breast cancer patients.

Lu CS, Huang SH, Ho CL, et al.
Primary neuroendocrine carcinoma of the breast.
J BUON. 2014 Apr-Jun; 19(2):419-29 [PubMed] Related Publications
PURPOSE: Primary neuroendocrine carcinoma of the breast (NECB) is a rare distinct type of breast carcinoma. There are only some case reports on this topic published in the past. There is still little known on the optimal treatment outcomes, while a wide variety of treatments is proposed by several authors. In this study we searched the literature on NECB in PubMed to clarify its prognosis and possible optimal therapeutic strategies.
METHODS: Eighty-six cases of primary NEC, included our case, were collected from PubMed between 1980 and 2013. Initial stage, estrogen receptor (ER)/progesterone receptor (PR)/ human epidermal growth factor receptor 2 (HER-2), surgical procedures, adjuvant treatment and overall survive (OS) were analyzed using the Statistical Package for the Social Sciences ( SPSS, v 16.0 ).
RESULTS: All 86 patients enrolled were eligible. Their mean age at diagnosis was 53.9 years (range 25-83) and 1 case was in a male. Overall survival (OS) at 48 months was 83.5%. Patients with enlarged tumor size (10 patients with tumor size >5.0 cm) or advanced stage (stage III 15 patients, stage IV 2 patients) had poor OS (48-month OS: 51.4 vs 97.1% with tumors >5cm vs ≤2cm, respectively and 0.0%, 68.1%, 72.9% and 95.8% in stage IV, III, II and I, respectively). Patients with positive ER, PR or HER-2 had significantly better OS than did those without (ER, p<0.001; PR, p<0.001; HER-2, p=0.082). Besides, all 60 patients with initial primary surgery and without lymph node dissection (LND) showed better OS than those with initial primary surgery without LND, the difference however being not significant (p=0.133).
CONCLUSION: Definite diagnosis and clinical stage are prerequisites in the initial approach in NECB. When detected early the disease may have a good prognosis with combined modality treatment such as chemotherapy, surgery, and radiation therapy. An appropriate therapeutic strategy for this group is also important. Our analysis showed that for patients with early localized disease only primary surgery is recommended and LND is optional. In patients with positive steroid receptors postoperative hormonotherapy is suggested.

Related: Breast Cancer

Helvie MA, Chang JT, Hendrick RE, Banerjee M
Reduction in late-stage breast cancer incidence in the mammography era: Implications for overdiagnosis of invasive cancer.
Cancer. 2014; 120(17):2649-56 [PubMed] Related Publications
BACKGROUND: Mammographic screening is expected to decrease the incidence of late-stage breast cancer. In the current study, the authors determined the decrease in late-stage cancer incidence and the changes in invasive cancer incidence that occurred in the mammographic era after adjusting for prescreening temporal trends.
METHODS: Breast cancer incidence and stage data were obtained from the Surveillance, Epidemiology, and End Results program. The premammography period (1977-1979) was compared with the mammographic screening period (2007-2009) for women aged ≥ 40 years. The authors estimated prescreening temporal trends using 5 measures of annual percentage change (APC). Stage-specific incidence values from 1977 through 1979 (baseline) were adjusted using APC values of 0.5%, 1.0%, 1.3%, and 2.0% and then compared with observed stage-specific incidence in 2007 through 2009.
RESULTS: Prescreening APC temporal trend estimates ranged from 0.8% to 2.3%. The joinpoint estimate of 1.3% for women aged ≥ 40 years approximated the 4-decade long APC trend of 1.2% noted in the Connecticut Tumor Registry. At an APC of 1.3%, late-stage breast cancer incidence decreased by 37% (56 cases per 100,000 women) with a reciprocal increase in early-stage rates noted from 1977 through 1979 to 2007 through 2009. Resulting late-stage cancer incidence decreased from 21% at an APC of 0.5% to 48% at an APC of 2.0%. Total invasive breast cancer incidence decreased by 9% (27 cases per 100,000 women) at an APC of 1.3%.
CONCLUSIONS: There is evidence that a substantial reduction in late-stage breast cancer has occurred in the mammography era when appropriate adjustments are made for prescreening temporal trends. At background APC estimates of ≥ 1%, the total invasive breast cancer incidence also decreased.

Related: Breast Cancer Cancer Screening and Early Detection USA

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

Hong W, Dong E
The past, present and future of breast cancer research in China.
Cancer Lett. 2014; 351(1):1-5 [PubMed] Related Publications
The incidence of breast cancer has increased rapidly in recent years and has now become the most common cancer in women in major cities of China. Here, we reviewed the history and progress of breast cancer research in China, including achievements that Chinese scientists have made in basic, translational and clinical research. Moreover, we evaluated the contributions of National Natural Science Foundation of China (NSFC) in the field of breast cancer research. The number of grants funded by the NSFC for breast cancer has tripled from 87 to 274 in the past 5years, and this resulted in a dramatic increase in breast cancer publications. Despite this great progress, policy makers are continuously taking efforts to guarantee the transparency of grant competition and the effective use of NSFC finding.

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

Brown PJ, Milch JM, Hivnor CM
Pigmented basal cell carcinoma of the nipple: a case report and review of the literature.
Cutis. 2013; 92(5):253-7 [PubMed] Related Publications
Although basal cell carcinoma (BCC) of the nipple-areola complex (NAC) is rare, it is important for dermatologists to be aware of this potential malignancy, as it is thought to behave more aggressively than BCC arising in other anatomic locations and also can mimic a number of more serious conditions. A review of the literature failed to generate a consensus regarding staging or treatment of BCC of the NAC; current therapies range from simple excision of the lesion to mastectomy with sentinel lymph node biopsy. We report the case of a 23-year-old man who presented with a pigmented BCC of the nipple to highlight several important aspects of the diagnosis; we also review 49 cases of BCC of the NAC from the literature and give our recommendations for treatment approach.

Related: Basal Cell Carcinoma Skin 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

Bradley KL, Tyldesley S, Speers CH, et al.
Contemporary systemic therapy for male breast cancer.
Clin Breast Cancer. 2014; 14(1):31-9 [PubMed] Related Publications
BACKGROUND: The use, effectiveness, and tolerability of tamoxifen, aromatase inhibitors, and trastuzumab in early and advanced male breast cancer were examined at a population level.
PATIENTS AND METHODS: A total of 158 consecutively referred men with invasive breast cancer diagnosed between 2000 and 2010 were identified. Stage and prognostic factors were compared with a random sample of contemporary female patients. Survival outcomes were compared with a separate female cohort matched 2:1 by prognostic and treatment factors.
RESULTS: Men were older (median 69.5 years) than women (median 60 years) and presented with more advanced stage disease. Estrogen receptor was positive in 96% (n = 152) of cases. Tamoxifen was more commonly used than aromatase inhibitors in the curative and metastatic settings. Adherence to adjuvant tamoxifen therapy was generally adequate with estimated actuarial rates of persistence at 1 year and 3.5 years of 89% and 70%, respectively. For the 146 men treated with curative intent, 5-year overall survival, breast cancer-specific survival and progression-free survival were 72%, 86%, and 62%, respectively. Outcomes were similar to matched female patients in univariate and multivariate analyses.
CONCLUSIONS: In this large population-based study, outcomes appear similar between male and risk-matched female patients with breast cancer. Side effect profiles, tolerance, adherence, and outcomes after tamoxifen, aromatase inhibitors, and trastuzumab in men appear comparable with those described in the literature for women.

Related: Breast Cancer Trastuzumab (Herceptin)

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.

Chen PH, Slanetz PJ
Incremental clinical value of ultrasound in men with mammographically confirmed gynecomastia.
Eur J Radiol. 2014; 83(1):123-9 [PubMed] Related Publications
PURPOSE: To determine whether ultrasound is of any value in male patients presenting with focal symptoms who have classic features of gynecomastia but no concerning findings on mammography.
MATERIALS AND METHODS: Over a 3-year period, all male patients who underwent mammographic evaluation were identified in this retrospective study. Patients with a mammographic diagnosis of gynecomastia and subsequent breast ultrasound at a large tertiary academic medical center comprised the study cohort. Men whose ultrasound diagnosis differed from the initial mammographic evaluation were analyzed for both additional benign findings as well as findings that warranted biopsy.
RESULTS: A total of 353 mammograms were obtained from 327 unique patients (ages 18-95, mean 51 years). Of all mammographic examinations, gynecomastia was the sole finding in 73% (259). In those 259 studies, 85% were further evaluated with ultrasound, in which 6 (2.7%) showed additional benign findings, and 4 (1.8%) showed suspicious findings for which biopsy was recommended. No malignancies were detected in those patients. Furthermore, no malignancies were detected in patients whose mammogram revealed only normal fatty parenchyma or only gynecomastia. In all cases of cancer, mammography revealed visible masses.
CONCLUSION: Judicious use of breast ultrasound in men improves outcome. Our data suggest that targeted ultrasound is of limited value in symptomatic male patients where mammography is negative or reveals only gynecomastia and leads to unnecessary benign biopsies in these patients. When mammography reveals concerning findings, ultrasound adds positively to clinical management.

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

Schildhaus HU, Schroeder L, Merkelbach-Bruse S, et al.
Therapeutic strategies in male breast cancer: clinical implications of chromosome 17 gene alterations and molecular subtypes.
Breast. 2013; 22(6):1066-71 [PubMed] Related Publications
Male breast cancer (MBC) is a rare disease. To date, therapy is mainly based on studies and clinical experiences with breast cancer in women. Only little is known about molecular typing of MBC, particularly with regard to potential biological predictors for adjuvant therapy. In female breast cancer tumors with chromosome 17 centromere (CEP17) duplication, HER2 and/or Topoisomerase II alpha (Topo II-α) gene alterations have been suggested to be associated with poor prognosis and increased sensitivity to anthracycline-containing regimens. In a well characterized cohort of 96 primary invasive MBC, we studied CEP17, HER2 and Topo II-α alterations by fluorescence in-situ hybridization (FISH), and expression of hormone receptors (HR), HER2 and Ki67 by immunohistochemistry to define molecular subtypes. Tumor characteristics and follow-up data were available and correlated with molecular findings. HER2 amplification and Topo II-α amplification/deletion were exceptionally rare in MBC (6.3% and 3.1%, respectively). CEP17 polysomy were found in 9.4% of tumors. HER2, Topo II-α and CEP17 gene alterations were not correlated to patients outcome. 96.9% of our cases were HR positive. Triple negative tumors were found in only 3.1% of the cases. In nodal negative tumors luminal A subtypes were significantly associated with better overall survival. Our results provide evidence for a predominant male breast cancer phenotype, characterized by HR expression and a lack of HER2/Topo II-α alterations and CEP17 duplicates. Therefore, the impact of anthracycline sensitivity linked to HER2/Topo II-α alterations as found in female breast cancer has low clinical significance for this specific male breast cancer phenotype.

Related: Chromosome 17 FISH MKI67

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.

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