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.
Macmillan Cancer Support Content is developed by a team of information development nurses and content editors, and reviewed by health professionals. Further info. Information on breast cancer in men, including how it is diagnosed, treatments you might have, possible side effects and how to get further support.
Dana-Farber Cancer Institute Michael, a breast cancer patient, shares his experiences, and Dr. Beth Overmoyer from the Dana-Farber Cancer Institute talks about the stigma associated with male breast cancer.
Malebreastcancer.ca A Website founded in 2008 by 2 daughters whose 61 yr old father was diagnosed with MBC. The associated organisation became a not-for-profit organization in Canada in 2011. The Website includes information and a firum and aims to raise awareness of MBC.
PubMed Central search for free-access publications about Male Breast Cancer MeSH term: Breast Neoplasms, Male US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
This list of publications is regularly updated (Source: PubMed).
Colfry AJ Miscellaneous syndromes and their management: occult breast cancer, breast cancer in pregnancy, male breast cancer, surgery in stage IV disease. Surg Clin North Am. 2013; 93(2):519-31 [PubMed]
Surgical therapy for occult breast cancer has traditionally centered on mastectomy; however, breast conservation with whole breast radiotherapy followed by axillary lymph node dissection has shown equivalent results. Patients with breast cancer in pregnancy can be safely and effectively treated; given a patient's pregnancy trimester and stage of breast cancer, a clinician must be able to guide therapy accordingly. Male breast cancer risk factors show strong association with BRCA2 mutations, as well as Klinefelter syndrome. Several retrospective trials of surgical therapy in stage IV breast cancer have associated a survival advantage with primary site tumor extirpation.
Alacacioglu A, Unal S, Canpolat S, et al. Breast metastasis of anaplastic oligodendroglioma: a case report. Tumori. 2012; 98(6):162e-4e [PubMed]
Extracranial metastasis of primary brain tumors is rarely observed. Of all brain malignancies, glioblastomas, medulloblastomas and astrocytomas metastasize most frequently. Metastasis of oligondendroglioma is rare. We present a case of breast metastasis in a 58-year-old man with an anaplastic oligodendroglioma.
Froehner M, Abolmaali N, Wirth MP Prostate-specific antigen-negative prostate cancer recurrence? Urology. 2013; 81(2):e17-8 [PubMed]
We describe a patient with bone metastases occurring shortly after radical prostatectomy for organ-confined prostate cancer. The medical history and immunohistochemical findings suggested prostate cancer recurrence to the skeleton. Undetectable serum prostate-specific antigen levels, however, raised doubts about this diagnosis. A whole body (18)F-fluorodeoxyglucose positron emission tomography-computed tomography scan was obtained and revealed a right-sided breast cancer as the primary site of metastatic spread.
Jacobs PA, Maloney V, Cooke R, et al. Male breast cancer, age and sex chromosome aneuploidy. Br J Cancer. 2013; 108(4):959-63 [PubMed] Article available free on PMC after 05/03/2014
BACKGROUND: In cultured, dividing transformed T lymphocytes and in dividing bone marrow cells from normal men and those with a haematological malignancy, sex chromosome aneuploidy has been found to increase in prevalence and degree with age. This has rarely been investigated in non-dividing uncultured blood samples. The loss and gain of the X chromosome in dividing transformed lymphocytes in women with age is much more frequent than that of the Y chromosome in males. However, paradoxically X chromosome aneuploidy is rarely seen in the dividing cells of bone marrow of females. METHODS: In blood samples from 565 men with breast cancer and 54 control men from the England and Wales general population, 80 cell nuclei per sample were scored for presence of X and Y chromosomes using fluorescent centromeric probes. RESULTS: Sex chromosome aneuploidy, largely Y chromosome loss, was present in 63% of cases and 57% of controls, with the prevalence and degree of aneuploidy increasingly sharply and highly significantly with age. At ages 65-80 years, 71% of cases and 85% of controls showed aneuploidy and 15% and 25%, respectively, had ≥ 10% of cells aneuploid. Allowing for age, aneuploidy was less prevalent (P=0.03) in cases than controls. CONCLUSION: Sex chromosome aneuploidy in non-dividing nuclei of peripheral blood cells is frequent in adult men, the prevalence and degree increasing sharply with age. The possible relation of sex chromosome aneuploidy to breast cancer risk in men, and to cancer risk generally, needs further investigation, ideally in cohort studies.
Weitzel JN, Clague J, Martir-Negron A, et al. Prevalence and type of BRCA mutations in Hispanics undergoing genetic cancer risk assessment in the southwestern United States: a report from the Clinical Cancer Genetics Community Research Network. J Clin Oncol. 2013; 31(2):210-6 [PubMed] Article available free on PMC after 10/01/2014
PURPOSE: To determine the prevalence and type of BRCA1 and BRCA2 (BRCA) mutations among Hispanics in the Southwestern United States and their potential impact on genetic cancer risk assessment (GCRA). PATIENTS AND METHODS: Hispanics (n = 746) with a personal or family history of breast and/or ovarian cancer were enrolled in an institutional review board-approved registry and received GCRA and BRCA testing within a consortium of 14 clinics. Population-based Hispanic breast cancer cases (n = 492) enrolled in the Northern California Breast Cancer Family Registry, negative by sequencing for BRCA mutations, were analyzed for the presence of the BRCA1 ex9-12del large rearrangement. RESULTS: Deleterious BRCA mutations were detected in 189 (25%) of 746 familial clinic patients (124 BRCA1, 65 BRCA2); 21 (11%) of 189 were large rearrangement mutations, of which 62% (13 of 21) were BRCA1 ex9-12del. Nine recurrent mutations accounted for 53% of the total. Among these, BRCA1 ex9-12del seems to be a Mexican founder mutation and represents 10% to 12% of all BRCA1 mutations in clinic- and population-based cohorts in the United States. CONCLUSION: BRCA mutations were prevalent in the largest study of Hispanic breast and/or ovarian cancer families in the United States to date, and a significant proportion were large rearrangement mutations. The high frequency of large rearrangement mutations warrants screening in every case. We document the first Mexican founder mutation (BRCA1 ex9-12del), which, along with other recurrent mutations, suggests the potential for a cost-effective panel approach to ancestry-informed GCRA.
Pinto R, Pilato B, Ottini L, et al. Different methylation and microRNA expression pattern in male and female familial breast cancer. J Cell Physiol. 2013; 228(6):1264-9 [PubMed]
Epigenetic regulation, has been very scarcely explored in familial breast cancer (BC). In the present study RASSF1A and RAR beta promoter methylation and miR17, miR21, miR 124, and let-7a expression were investigated to highlight possible differences of epigenetic regulation between male and female familial BC, also in comparison with sporadic BC. These epigenetic alterations were studied in 56 familial BC patients (27 males and 29 females) and in 16 female sporadic cases. RASSF1A resulted more frequently methylated in men than women (76% vs. 28%, respectively, P = 0.0001), while miR17 and let-7a expression frequency was higher in women than in men (miR17: 66% in women vs. 41% in men, P < 0.05; let-7a: 45% in women vs. 15% in men, P = 0.015). RASSF1A methylation affected 27.6% of familial BC while 83% of familial cases showed high expression of the gene (P = 0.025); on the contrary, only 17% of familial BC presented RAR beta methylation and 55% of familial cases overexpressed this gene (P = 0.005). Moreover, miR17, miR21, and let-7a resulted significantly overexpressed in familial compared to sporadic BC. RASSF1A overexpression (86% vs. 65%, P = 0.13) and RAR beta overexpression (57% vs. 32%, P = 0.11) were higher in BRCA1/2 carriers even if not statistical significance was reached. BRCA mutation carriers also demonstrated significant overexpression of: miR17 (93% vs. 35%, P = 0.0001), let-7a (64% vs. 16%, P = 0.002), and of miR21 (100% vs. 65%, P = 0.008). In conclusion, the present data suggest the involvement of RASSF1A in familial male BC, while miR17 and let-7a seem to be implied in familial female BC.
Tural D, Selçukbiricik F, Aydoğan F, et al. Male breast cancers behave differently in elderly patients. Jpn J Clin Oncol. 2013; 43(1):22-7 [PubMed]
OBJECTIVE: The aim of this study was to evaluate tumor characteristics, management and survival in elderly male breast cancer patients in comparison with younger men. METHODS: We reviewed medical records of 99 male breast cancer patients between 1972 and 2011. The median age of the patients was 64.5 years. Patient characteristics including clinicopathologic factors, treatment modalities, survival and prognostic factors were evaluated. Patients were subdivided into two groups according to their age (young, <65 years; old, ≥ 65 years) and compared based on these factors. RESULTS: Elderly male breast cancer patients had larger tumors in more advanced stages at the time of diagnosis compared with younger patients. In spite of the larger tumors at presentation, older patients had tumors with more favorable biological characteristics, such as higher ratio of estrogen and progesterone receptor expression. Ten-year cancer-specific survival for older patients was 49.2% compared with 55.8% in younger men (P = 0.8). Prognostic factors influencing overall survival in univariate analysis were: the presence of metastatic axillary lymph nodes (P = 0.0001), T stage (P = 0.001) and age ≥ 65 years. Multivariate analysis indicated T stage (P = 0.008) and N stage (P = 0.038) as the significant negative prognostic factors for overall survival. Although surgery, radiotherapy and hormone therapy were equally utilized in old and young patients, old patients were less likely to receive adjuvant chemotherapy. CONCLUSIONS: Our study demonstrated the differences in the clinical and biological characteristics of male breast cancer according to the age of the patients.
Holliday DL, Moss MA, Pollock S, et al. The practicalities of using tissue slices as preclinical organotypic breast cancer models. J Clin Pathol. 2013; 66(3):253-5 [PubMed]
Models considering breast cancer complexity cannot be easily or accurately replicated in routine cell line or animal models. We aimed to evaluate the practicality of organotypic tissue slice culture in breast cancer. Following ethical approval, 250 µm thick sections from surplus breast tumours (n=10) were prepared using a vibrating blade microtome. Triplicate tissue slices were placed in 6-well plates and cultured for up to 7 days ± tamoxifen (1 nM) or doxorubicin (1 µM). Tissue slices were fixed and embedded before sectioning for morphological evaluation and immunohistochemistry. H&E showed good preservation of tissue morphology. Collagen production was evident. Biomarkers of proliferation and apoptosis could be evaluated using immunohistochemistry and used as surrogates to quantify drug effects. In summary, breast cancer tissue slices can be cultured in vitro as organotypic models. Nevertheless, although simple in concept, the delicacy of the model with regard to handling makes subsequent analytical processes challenging.
Toesca A, Spitaleri G, De Pas T, et al. Sarcoma of the breast: outcome and reconstructive options. Clin Breast Cancer. 2012; 12(6):438-44 [PubMed]
INTRODUCTION: Surgery is the mainstay of treatment for all breast sarcomas. The role of adjuvant chemotherapy and radiation therapy has not been clearly defined. The aim of this single-center retrospective study was to analyze prognostic factors, outcome, and recent advances. MATERIALS AND METHODS: Data from 203 patients with all breast sarcomas treated in a single center were collected from 1996 to 2010. Phyllodes tumors and metastatic disease at presentation were excluded from the population. Thirty-six women and 1 man were included in the analysis. Local recurrence, metastatic disease, survival, and reconstructive outcome were evaluated. RESULTS: Thirty-four patients out of 37 (91.9%) had an angiosarcoma and 3 had a stromal sarcoma (8.1%). Twenty-one patients (56.8%) had previously undergone breast radiation therapy for breast carcinoma or lymphoma. Twenty-six patients (70.3%) underwent mastectomy, 14 of whom (53.8%) with breast reconstruction. Thirty-six patients (97.3%) had free margins, 1 (2.7%) had a microscopically focally involved margin after surgery. Five patients received adjuvant chemotherapy and 6 received adjuvant radiation therapy. Median follow-up was 58 months (range, 4-146 months). Twelve sarcoma-related deaths were observed with a 5-year cumulative incidence of 43.4%. Twenty-four sarcoma-related events were observed with a 5-year cumulative incidence of 70.8%. The same figure was 49.7% in patients affected by primary sarcoma and 85.7% in patients with secondary sarcoma (P = .06). CONCLUSION: Secondary sarcomas were associated with a higher risk of events. Patients undergoing breast conservative surgery or reconstruction after mastectomy did not show a worse prognosis compared with patients undergoing mastectomy.
Shin SR, Lee MS, Park SH, et al. A case of breast cancer in a male patient with cryptogenic cirrhosis. Korean J Gastroenterol. 2012; 60(3):182-5 [PubMed]
Breast cancer is a rare disease in men. We report a case of 53-year-old obese male, with known cryptogenic cirrhosis and hepatocellular carcinoma, presenting a tender mass on left breast. He was diagnosed with invasive intraductal carcinoma, which was consistent with a sporadic lesion. On the basis of previous literatures, obesity can be regarded as a cause for breast cancer even in men. However, there has been inconsistent data about link between liver cirrhosis and male breast cancer, which can be due to heterogenity in the etiology of cirrhosis. Through this case, it can be postulated that the risk for male breast cancer may vary according to the etiology of cirrhosis.
Orr N, Lemnrau A, Cooke R, et al. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk. Nat Genet. 2012; 44(11):1182-4 [PubMed]
We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 × 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10(-15); OR = 1.50).
Sánchez-Muñoz A, Román-Jobacho A, Pérez-Villa L, et al. Male breast cancer: immunohistochemical subtypes and clinical outcome characterization. Oncology. 2012; 83(4):228-33 [PubMed]
AIM: The aim of this study was to assess the molecular subtype profiles of male breast cancer (MBC) and subsequent clinical outcome using a validated 6-marker immunohistochemical panel. METHODS: A total of 43 cases of MBC were examined retrospectively using a semiquantitative immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (Her2), epidermal growth factor receptor and cytokeratin 5/6. Patients were classified into the following categories: luminal A, luminal B, Her2-positive or basal-like subtypes. RESULTS: The median age of patients was 63 years (r: 32-89). The predominant histology was invasive ductal carcinoma (91%). Only 1 patient had advanced breast cancer at diagnosis. Ninety-three percent were ER-positive and 84% were PR-positive. Two patients had tumors that were ER- and PR-negative. The distribution of tumor molecular subtypes was 19 (44%) luminal A, 22 (51%) luminal B and 2 (5%) basal-like. The Her2-positive tumor subtype was not identified. The clinicopathological characteristics did not differ significantly between tumor subtypes A and B. There were no significant differences in 6-year disease-free survival (74 vs. 82%, p = 0.77) or overall survival (74 vs. 82%, p = 0.69) between luminal A and luminal B subtypes, respectively. CONCLUSION: The most common subtypes in our cohort of MBC were luminal B followed by luminal A, and no differences were found between both tumor subtypes in terms of clinicopathologic characteristics and patient outcome.
Delpech Y, Wu Y, Hess KR, et al. Ki67 expression in the primary tumor predicts for clinical benefit and time to progression on first-line endocrine therapy in estrogen receptor-positive metastatic breast cancer. Breast Cancer Res Treat. 2012; 135(2):619-27 [PubMed]
We examined whether baseline Ki67 expression in estrogen receptor-positive (ER+) primary breast cancer correlates with clinical benefit and time to progression on first-line endocrine therapy and survival in metastatic disease. Ki67 values and outcome information were retrieved from a prospectively maintained clinical database and validated against the medical records; 241 patients with metastatic breast cancer were included--who had ER+ primary cancer with known Ki67 expression level--and received first-line endocrine therapy for metastatic disease. Patients were assigned to low (<10 %), intermediate (10-25 %), or high (>25 %) Ki67 expression groups. Kaplan-Meier survival curves were plotted and multivariate analysis was performed to assess association between clinical and immunohistochemical variables and outcome. The clinical benefit rates were 81, 65, and 55 % in the low (n = 32), intermediate (n = 103), and high (n = 106) Ki67 expression groups (P = 0.001). The median times to progression on first-line endocrine therapy were 20.3 (95 % CI, 17.5-38.5), 10.8 (95 % CI, 8.9-18.8), and 8 (95 % CI, 6.1-11.1) months, respectively (P = 0.0002). The median survival times after diagnosis of metastatic disease were also longer for the low/intermediate compared to the high Ki67 group, 52 versus 30 months (P < 0.0001). In multivariate analysis, high Ki67 expression in the primary tumor remained an independent adverse prognostic factor in metastatic disease (P = 0.001). Low Ki67 expression in the primary tumor is associated with higher clinical benefit and longer time to progression on first-line endocrine therapy and longer survival after metastatic recurrence.
Koukouras D, Spyropoulos C, Zygomalas A, Tzoracoleftherakis E Sentinel node biopsy in male breast carcinoma: is the "female" approach justified? Eur J Gynaecol Oncol. 2012; 33(3):255-6 [PubMed]
PURPOSE: Mastectomy with axillary lymph node dissection (ALND) represents the gold standard in the treatment of male breast carcinoma. Recently, data have emerged supporting that sentinel lymph node biopsy (SNB) may be feasible in selected patients. The aim of this study was to analyze the safety and prognostic reliability of SNB in male patients with breast carcinoma and clinically negative axilla. METHODS: During a 10-year period (2000-2010), 11 men with mean age 66.1 years (range 34-84) diagnosed with breast carcinoma were retrospectively included to our study. All patients underwent SNB. Regardless of the SNB results, completion axillary clearance was conducted in all cases. RESULTS: SNB detection rate was 100%, while the mean number of sentinel nodes removed was 1.5 +/- 0.7 (range 1-2). Frozen section analysis revealed a negative sentinel node in four out of 11 patients (36.4%). Independently of these results, all patients underwent completion ALND. The overall false-negative rate, defined as the percentage of all node-positive tumors in which the SNB was negative, was 0%. CONCLUSION: The current study indicates that SNB may be feasible in selected male individuals with breast carcinoma. The technique may reduce the morbidity related to dissection of the axilla; prospective multicenter trials are needed in order to define the exact criteria for wider application of this technique.
Müller AC, Gani C, Rehm HM, et al. Are there biologic differences between male and female breast cancer explaining inferior outcome of men despite equal stage and treatment?! Strahlenther Onkol. 2012; 188(9):782-7 [PubMed]
BACKGROUND: Reasons for inferior outcome of male compared to female breast cancer are still under debate. Therefore, we retrospectively analyzed male breast cancer cases to figure out possible treatment- and gender-related differences. PATIENTS AND METHODS: A total of 40 men (median age 62 years) were curatively treated with mastectomy and postoperative radiotherapy from 1982-2007. They presented predominantly in stages II and IIIb. Postoperative radiotherapy was applied with doses of 1.8-2.5 Gy to a median of 50 Gy including regional lymphatics in 22 patients. Adjuvant systemic treatment consisted of chemotherapy (22.5%) and antihormonal treatment (55%). For reasons of comparison, we estimated outcome of a virtual female matched cohort for no/equal to men/optimal adjuvant treatment with the Adjuvant!Online(®) 8.0 algorithm. RESULTS: After a median follow-up of 47 months, the estimated 5-year local control rate was 97%, disease-free and distant metastasis-free survival rates reached 79% and 82%, respectively. With update of survival data by tumor registry, mean overall survival reached 120 months with 5- and 10-year overall survival rates of 66% and 43%, respectively. Predominant prognostic factor was T-stage for overall survival (T1/2 vs. T4: > 80% vs. 30%). The generated virtual matched cohorts of women with equal characteristics reached superior 10-year-overall survival for no/equal to men/optimal adjuvant treatment with 55/59/68%. CONCLUSION: Compared to historical and virtual matched cohorts of women, male breast cancer patients had inferior outcome despite of equal stage and treatment which indicates that biological differences (of tumor or population) may contribute to worse prognosis.
Shannon KM, Chittenden A Genetic testing by cancer site: breast. Cancer J. 2012 Jul-Aug; 18(4):310-9 [PubMed]
Women in the United States have a 12% lifetime risk of developing breast cancer. Although only about 5% to 10% of all cases of breast cancer are attributable to a highly penetrant cancer predisposition gene, individuals who carry a mutation in one of these genes have a significantly higher risk of developing breast cancer, as well as other cancers, over their lifetime compared with the general population. The ability to distinguish those individuals at high risk allows health care providers to intervene with appropriate counseling and education, surveillance, and prevention-with the overall goal of improved survival for these individuals. This article focuses on the identification of patients at high risk for breast cancer and provides an overview of the clinical features, cancer risks, causative genes, and medical management for the most clearly described hereditary breast cancer syndromes. Newer genes that have also been implicated in familial breast cancer are also briefly reviewed.
Teo JY, Tan PH, Yong WS Male breast cancer in Singapore: 15 years of experience at a single tertiary institution. Ann Acad Med Singapore. 2012; 41(6):247-51 [PubMed]
INTRODUCTION: Male breast cancer is a rare disease entity, with little data from the Southeast Asian perspective. Hence, this study aims to review the data from our local experience in order to better delineate the disease characteristics in our population. MATERIALS AND METHODS: Male patients with histologically proven breast cancer were identified from a prospectively collected database. The clinical, histopathological and survival data were reviewed retrospectively and analysed. RESULTS: Twenty-one patients were identified. The median age at diagnosis was 68 years. Eighteen patients underwent simple mastectomy with curative intent, with the remaining patients having metastatic disease at presentation. Almost half of the patients presented with stage III or IV disease. At the time of analysis, median overall survival was 50 months and median disease-free survival was 47.5 months. None of the patients had any documented family history or risk factors for male breast cancer. CONCLUSION: The disease appears to be a sporadic and rare occurrence in the local male population. A high index of suspicion should be maintained in males presented with a unilateral breast lump so that appropriate treatment can be instituted.
Vinh-Hung V, Everaert H, Lamote J, et al. Diagnostic and prognostic correlates of preoperative FDG PET for breast cancer. Eur J Nucl Med Mol Imaging. 2012; 39(10):1618-27 [PubMed]
PURPOSE: To explore the preoperative utility of FDG PET for the diagnosis and prognosis in a retrospective breast cancer case series. METHODS: In this retrospective study, 104 patients who had undergone a preoperative FDG PET scan for primary breast cancer at the UZ Brussel during the period 2002-2008 were identified. Selection criteria were: histological confirmation, FDG PET performed prior to therapy, and breast surgery integrated into the primary therapy plan. Patterns of increased metabolism were recorded according to the involved locations: breast, ipsilateral axillary region, internal mammary chain, or distant organs. The end-point for the survival analysis using Cox proportional hazards was disease-free survival. The contribution of prognostic factors was evaluated using the Akaike information criterion and the Nagelkerke index. RESULTS: PET positivity was associated with age, gender, tumour location, tumour size >2 cm, lymphovascular invasion, oestrogen and progesterone receptor status. Among 63 patients with a negative axillary PET status, 56 (88.9 %) had three or fewer involved nodes, whereas among 41 patients with a positive axillary PET status, 25 (61.0 %) had more than three positive nodes (P < 0.0001). In the survival analysis of preoperative characteristics, PET axillary node positivity was the foremost statistically significant factor associated with decreased disease-free survival (hazard ratio 2.81, 95% CI 1.17-6.74). CONCLUSION: Preoperative PET axillary node positivity identified patients with a higher burden of nodal involvement, which might be important for treatment decisions in breast cancer patients.
Kornegoor R, Verschuur-Maes AH, Buerger H, et al. Fibrotic focus and hypoxia in male breast cancer. Mod Pathol. 2012; 25(10):1397-404 [PubMed]
Fibrotic focus is a scar-like lesion near the center of a carcinoma and has been associated with high-grade, lymph node metastases and poor survival in female breast cancers. Hypoxia is suggested to be the crucial link between fibrotic focus and aggressive tumor phenotype and is also itself a poor prognostic marker. We here set out to study fibrotic focus and hypoxia in male breast cancer for the first time. In a group of 134 male breast cancer patients, the presence and size of a fibrotic focus and the expression of three hypoxia-related immunohistochemical stainings, hypoxia-inducible factor-1α, carbonic anhydrase IX and Glut-1 were studied in correlation with clinicopathological features and prognosis. Fibrotic focus was seen in 25% of the male breast cancer cases and was correlated with hypoxia-inducible factor-1α overexpression (P=0.023), high grade (P=0.005), high mitotic activity (P=0.005) and lymph node metastases (P=0.037). Hypoxia-inducible factor-1α-positive tumors were more often high grade (P=0.003) and HER2 amplified (P=0.005). Glut-1 expression was also more common in grade 3 tumors (P=0.038), but no association between carbonic anhydrase IX and any clinicopathological feature was found. Fibrotic focus >8 mm and hypoxia-inducible factor-1α overexpression were correlated with decreased patients' outcome (P=0.035 and 0.008, respectively). Hypoxia-inducible factor-1α overexpression was an independent and the most powerful predictor of survival in multivariate analysis (P=0.029; hazard ratio 2.5). In conclusion, the presence of a fibrotic focus is associated with hypoxia-inducible factor-1α overexpression, and both are associated with aggressive tumor phenotype and poor survival in male breast cancer. These markers seem to have similar clinical importance as previously reported in female breast cancer.
Bardhan P, Bui MM, Minton S, et al. HER2-positive male breast cancer with thyroid cancer: an institutional report and review of literature. Ann Clin Lab Sci. 2012; 42(2):135-9 [PubMed]
We report a rare finding of two male breast cancer patients with HER2-positive breast cancer who also developed thyroid cancer. We reviewed 45 male breast cancer patients treated in our institution from 2003 to 2008. Only five male breast cancer patients were HER2-positive. In reviewing the published data, we found no cases of thyroid cancer and concurrent breast cancer in men. However, breast cancer and thyroid cancer have shown close association in women. This finding therefore provokes speculation as to whether we should investigate whether women with HER2-positive breast cancer are at a higher risk for thyroid cancer. Although this observation seems to be clinically prevalent, publications are sparse in clinical research areas linking thyroid cancer to breast cancer.
Abdel-Aal AK, Underwood ES, Saddekni S Use of cryoablation and osteoplasty reinforced with Kirschner wires in the treatment of femoral metastasis. Cardiovasc Intervent Radiol. 2012; 35(5):1211-5 [PubMed]
PURPOSE: We report the case of a 43-year-old man with metastatic breast carcinoma to the proximal right femur resulting in severe painful pathological fracture. The patient experienced severe pain despite large doses of analgesia, resulting in impaired functionality and quality of life. The patient had significant comorbidities, making him a high surgical risk. MATERIALS AND METHODS: The patient was treated with cryoablation and osteoplasty, followed by a novel technique consisting of osteoplasty reinforced with bone marrow Kirschner wires (K-wires) which will be described in details in this report. RESULTS: The patient reported significant pain relief after the procedure, and gained right lower extremity functionality, as compared to total immobility before the procedure. CONCLUSION: Our technique offers an alternative feasible treatment for patients at high surgical risk with pathological fractures in weight-bearing bones, in which osteoplasty alone has a high risk of cement leakage, inadequate fracture reduction, and early refracture. To our knowledge, our technique has not been previously described.
Gutsche M, Kuschner WG Hemoptysis due to breath-hold diving following chemotherapy and lung irradiation. Clin Med Res. 2012; 10(3):137-9 [PubMed] Article available free on PMC after 10/01/2014
Breath-hold diving, also known as free-diving, describes the practice of intentional immersion under water without an external supply of oxygen. Pulmonary hemorrhage with hemoptysis has been reported as a complication of immersion and breath-hold diving in young healthy athletes. We report the case of a 60-year-old man with a history of radiation and chemotherapy for breast carcinoma, who developed the abrupt onset of hemoptysis in the setting of swimming and breath-hold diving. A computed tomography (CT) scan of the chest demonstrated an area of ground glass opacification, suggestive of pulmonary hemorrhage, superimposed on a background of reticular opacities within the prior radiation field. A follow-up CT scan of the chest, obtained 2 months after presentation, demonstrated resolution of the ground glass opacification, but persistence of fibrotic features attributable to prior radiation therapy. We postulate that prior irradiation of the chest resulted in lung injury and fibrosis which, in turn, rendered the affected region of the lung susceptible to "stress failure," due to an increase in the transcapillary pressure gradient arising from immersion and breath-hold diving. Patients with a history of lung injury resulting from chest irradiation should be cautioned about pulmonary hemorrhage and hemoptysis as a potential complication of swimming and breath-hold diving.
Ottini L, Silvestri V, Rizzolo P, et al. Clinical and pathologic characteristics of BRCA-positive and BRCA-negative male breast cancer patients: results from a collaborative multicenter study in Italy. Breast Cancer Res Treat. 2012; 134(1):411-8 [PubMed]
Recently, the number of studies on male breast cancer (MBC) has been increasing. However, as MBC is a rare disease there are difficulties to undertake studies to identify specific MBC subgroups. At present, it is still largely unknown whether BRCA-related breast cancer (BC) in men may display specific characteristics as it is for BRCA-related BC in women. To investigate the clinical-pathologic features of MBC in association with BRCA mutations we established a collaborative Italian Multicenter Study on MBC with the aim to recruit a large series of MBCs. A total of 382 MBCs, including 50 BRCA carriers, were collected from ten Italian Investigation Centres covering the whole country. In MBC patients, BRCA2 mutations were associated with family history of breast/ovarian cancer (p<0.0001), personal history of other cancers (p=0.044) and contralateral BC (p=0.001). BRCA2-associated MBCs presented with high tumor grade (p=0.001), PR-(p=0.026) and HER2+ (p=0.001) status. In a multivariate logistic model BRCA2 mutations showed positive association with personal history of other cancers (OR 11.42, 95% CI 1.79-73.08) and high tumor grade (OR 4.93, 95% CI 1.02-23.88) and inverse association with PR+ status (OR 0.19, 95% CI 0.04-0.92). Based on immunohistochemical (IHC) profile, four molecular subtypes of MBC were identified. Luminal A was the most common subtype (67.7%), luminal B was observed in 26.5% of the cases and HER2 positive and triple negative were represented by 2.1% and 3.7% of tumors, respectively. Intriguingly, we found that both luminal B and HER2 positive subtypes were associated with high tumor grade (p=0.003 and 0.006, respectively) and with BRCA2 mutations (p=0.016 and 0.001, respectively). In conclusion, our findings indicate that BRCA2-related MBCs represent a subgroup of tumors with a peculiar phenotype characterized by aggressive behavior. The identification of a BRCA2-associated phenotype might define a subset of MBC patients eligible for personalized clinical management.
Kornegoor R, Moelans CB, Verschuur-Maes AH, et al. Oncogene amplification in male breast cancer: analysis by multiplex ligation-dependent probe amplification. Breast Cancer Res Treat. 2012; 135(1):49-58 [PubMed] Article available free on PMC after 10/01/2014
Gene amplification is an important mechanism for oncogene activation, a crucial step in carcinogenesis. Compared to female breast cancer, little is known on the genetic makeup of male breast cancer, because large series are lacking. Copy number changes of 21 breast cancer related genes were studied in 110 male breast cancers using multiplex ligation-dependent probe amplification. A ratio of >1.3 was regarded indicative for gene copy number gain and a ratio >2.0 for gene amplification. Data were correlated with clinicopathological features, prognosis and 17 genes were compared with a group of female breast cancers. Gene copy number gain of CCND1, TRAF4, CDC6 and MTDH was seen in >40 % of the male breast cancer cases, with also frequent amplification. The number of genes with copy number gain and several single genes were associated with high grade, but only CCND1 amplification was an independent predictor of adverse survival in Cox regression (p = 0.015; hazard ratio 3.0). In unsupervised hierarchical clustering a distinctive group of male breast cancer with poor prognosis (p = 0.009; hazard ratio 3.4) was identified, characterized by frequent CCND1, MTDH, CDC6, ADAM9, TRAF4 and MYC copy number gain. Compared to female breast cancers, EGFR (p = 0.005) and CCND1 (p = 0.041) copy number gain was more often seen in male breast cancer, while copy number gain of EMSY (p = 0.004) and CPD (p = 0.001) and amplification in general was less frequent. In conclusion, several female breast cancer genes also seem to be important in male breast carcinogenesis. However, there are also clear differences in copy number changes between male and female breast cancers, pointing toward differences in carcinogenesis between male and female breast cancer and emphasizing the importance of identifying biomarkers and therapeutic agents based on research in male breast cancer. In addition CCND1 amplification seems to be an independent prognosticator in male breast cancer.
de Ieso PB, Potter AE, Le H, et al. Male breast cancer: a 30-year experience in South Australia. Asia Pac J Clin Oncol. 2012; 8(2):187-93 [PubMed]
AIMS: Male breast cancer (MBC) is an uncommon disease with a paucity of information in the literature. The treatment of MBC has traditionally been extrapolated from experience with female breast cancer. This study reports on the treatment and outcomes of this disease in South Australia over a 30-year period. METHODS: From 1977 to 2007 63 patients with a median age of 62 years (range 33-85 years) were identified and treated for MBC. Data obtained, included initial stage, pathological features, treatment and outcomes. RESULTS: With a median follow up of 4.9 years (range 2 months to 19 years) the 5-year overall survival (OS) rate was 85% with median survival of 5.5 years. In all, 18 (29%) were diagnosed with recurrent disease, while 45 (72%) remained disease free. The median time to recurrence was 2.5 years. One patient failed locally, three (4%) had locoregional recurrence and distant recurrence was noted in 14 patients (22%). Disease stage at presentation was a significant predictor of 5-year OS and recurrence (P = 0.012 and P = 0.0001). Tumor diameter was also a significant predictor of 5-year OS and recurrence (P = 0.006 and P = 0.021). CONCLUSION: This retrospective series has a 5-year OS that compares favorably with other published series of MBC. The positive findings may help change the misperception that MBC is an inherently aggressive disease process with a poor clinical outcome. Further studies are needed to carefully and thoroughly investigate this rare but treatable disease.
Eryilmaz MA, Igci A, Muslumanoglu M, et al. Male breast cancer: a retrospective study of 15 years. J BUON. 2012 Jan-Mar; 17(1):51-6 [PubMed]
PURPOSE: To retrospectively evaluate the 15-year experience with breast cancer in males at a single institution. METHODS: The data from 25 male patients who had undergone surgery for breast cancer at a single center were retrospectively analysed. Their medical records were studied for clinical characteristics, therapeutic modalities used and factors associated with disease free (DFS) and overall survival (OS), like local recurrence/distant metastasis. RESULTS: The median patient age was 67 years (range 38-83). The most frequent presenting symptom was a palpable lump. Eighteen (72%) patients underwent modified radical mastectomy (MRM), while sentinel lymph node biopsy (SLNB) was performed in 14 (56%) cases. Of 25 patients, 21 (84%) underwent axillary lymph node dissection (ALND) and 15 (71.4%) of them had pathological axillary lymph node involvement. Two of 25 (8%) patients with bone and liver metastases underwent toilet mastectomy due to breast ulceration. Estrogen receptor (ER) was positive in 15 (60%) patients, while progesterone receptor (PR) and C-erbB2 (HER-2) were positive in 10 (40%) and 2 (8%) patients, respectively. Ten patients (40%) had both ER(+) and PR(+). The median follow-up period was 19 months (range 3-102). Local recurrence developed in one (4%) patient and distant metastasis in 4 (16%). Five-year OS and DFS were 53 and 49%, respectively. In univariate and multivariate analysis, pathological tumor size (<2 vs. >2 cm), pathological lymph node involvement and preoperative skin involvement over the breast were not associated with breast recurrence. Only in univariate analysis local recurrence/distant metastasis were associated with poor OS. CONCLUSION: Large cooperative studies are needed using strict clinical and laboratory criteria to advance the understanding of this disease and to identify the most effective treatment approaches.
Al-Naggar RA, Al-Naggar DH Perceptions and opinions about male breast cancer and male breast self-examination: a qualitative study. Asian Pac J Cancer Prev. 2012; 13(1):243-6 [PubMed]
OBJECTIVE: While the relatively common nature of female breast cancer has resulted in a high level of general awareness, male breast cancer is still comparatively unknown to the general public and to healthcare professionals. The objective of this study is to explore the perceptions and opinions about male breast cancer and male breast self-examination among male university students. METHODOLOGY: In-depth interviews were conducted among 36 male university students from the Management and Science University, Malaysia, selected by simple random sampling. The themes of the interview were: knowledge of male breast cancer and male breast self-examination, sources of knowledge and attitudes towards male BSE. The data obtained were classified into various categories and analyzed manually. RESULTS: The majority of participants mentioned that there is a low possibility for males to get breast cancer. They also believed that the cause of breast cancer among men is due to the carcinogens from cigarettes. The majority of participants mentioned that they know about breast self-examination from the mass media and that the presence of a lump in the breast is the main symptom of breast cancer in men. The majority of participants mentioned that they encourage their family members to practice breast self-examination but considered that BSE is not important for men because they have a low probability of getting breast cancer. CONCLUSIONS: Misconceptions regarding male breast cancer and breast self-examination among men still exist among male university students. Therefore special attention should be given to educate men about male breast cancer and male BSE.
Zygogianni AG, Kyrgias G, Gennatas C, et al. Male breast carcinoma: epidemiology, risk factors and current therapeutic approaches. Asian Pac J Cancer Prev. 2012; 13(1):15-9 [PubMed]
Male breast cancer is a very rare disease with an incidence of about 0.5-1% comparing with the one of female breast cancer but relatively little is known about its cause. Treatment strategies for breast cancer in males are derived from studies performed among females. The probable reasons behind the frequent, late diagnoses presented at stages III or IV might be the lack of awareness. The rarity of the disease precludes large prospective randomized clinical trials. This study reviews male breast cancer and its risk factors, recommendations for diagnosis and the management of patients with male breast cancer.
Martín M, Makhson A, Gligorov J, et al. Phase II study of bevacizumab in combination with trastuzumab and capecitabine as first-line treatment for HER-2-positive locally recurrent or metastatic breast cancer. Oncologist. 2012; 17(4):469-75 [PubMed] Article available free on PMC after 10/01/2014
We report the first results from a phase II, open-label study designed to evaluate the efficacy and safety of bevacizumab in combination with trastuzumab and capecitabine as first-line therapy for human epidermal growth factor receptor (HER)-2-positive locally recurrent (LR) or metastatic breast cancer (MBC). Patients were aged ≥18 years with confirmed breast adenocarcinoma, measurable LR/MBC and documented HER-2-positive disease. Patients received bevacizumab (15 mg/kg on day 1) plus trastuzumab (8 mg/kg on day 1 of cycle 1, 6 mg/kg on day 1 of each subsequent cycle) plus capecitabine (1,000 mg/m2 twice daily, days 1-14) every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. Eighty-eight patients were enrolled; 40 (46%) are still on study treatment. The median follow-up was 8.8 months (range, 0.9-17.1 months). The overall response rate, the primary endpoint, was 73% (95% confidence interval [CI], 62%-82%), comprising 7% complete and 66% partial responses. The median progression-free survival interval was 14.4 months (95% CI, 10.4 months to not reached [NR]), with 35 events. The median time to progression was 14.5 months (95% CI, 10.5 months to NR), with 33 events. Treatment was well tolerated; main side effects were grade 3 hand-foot syndrome (22%), grade ≥3 diarrhea (9%), and grade ≥3 hypertension (7%). Overall, 44% of patients experienced grade ≥3 treatment-related adverse events and 13 patients discontinued capecitabine because of toxicity, but continued with bevacizumab and trastuzumab. Heart failure was seen in two patients. The combination of bevacizumab, trastuzumab, and capecitabine was clinically active as first-line therapy for patients with HER-2-positive MBC, with an acceptable safety profile and no unexpected toxicities.
Kulkarni MP, Gosavi AV, Ramteerthakar NA, et al. Intracystic papillary carcinoma of the breast: report of two cases. Breast Dis. 2011; 33(3):121-4 [PubMed]
Intracystic papillary carcinoma (IPC) of the breast has traditionally been considered to be a variant of ductal carcinoma in-situ (DCIS). It is an uncommon tumor accounting for less than 3% of all breast cancers and predominantly affects elderly women. IPC is extremely rare in men and only few cases have been reported in the literature. The tumor has excellent prognosis regardless of whether it is in-situ or invasive. Hence an accurate diagnosis plays a crucial role in the management of patients with IPC. We report two cases of IPC, one in a 68-year-old woman and the other one in a 70-year-old man. The diagnosis was suspected on fine needle aspiration cytology (FNAC) and was confirmed by histopathology.
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