Top 100 cited articles in male breast cancer: A bibliometric analysis.

BACKGROUND: Male breast cancer is a considerably rare condition and only accounts for 1% of all breast cancer cases. Due to limited public awareness, the condition is likely to present late, leading to late diagnosis and treatment worsening morbidity and mortality. This article aims to identify the focus and most influential research on male breast cancer. Objective Identify the most influential papers in male breast cancer. METHODS: Search on Web of Science using the search terms 'Male', 'Breast Cancer' and "Male breast cancer" to identify all full manuscripts in English language and were ranked by the total number of citations. The top 100 articles were then further analysed according to subject, author, journal, year and country of publications. RESULTS: The mean number of citations per paper was 96. Most cited paper was by Thorlacius, S et al. evaluating the relationship between BRCA2 and female breast cancer, prostate cancer, pancreatic cancer and ovarian cancer. Cancer is the journal with the most published papers and received most citations in the male breast cancer research field. The USA contributed 49 of the manuscripts in the top 100. The most studied topic was risk factors for male breast cancer, with 20 articles. CONCLUSIONS: The most cited papers identified in this study described the advance in the knowledge of genetics and epidemiology in male breast cancer and has led to improvements in the 4 management of the disease. Most of the highly cited articles in this field were published in high impact journals and had accumulated at least 100 citations to date, reflecting their quality and impact. By collating the most influential publications in this field, this analysis can serve to identify knowledge gaps in male breast cancer research as well as to help identify what makes a paper impactful and citable.

Cytoplasmic DDX3 as prognosticator in male breast cancer.

Male breast cancer (MBC) is a rare disease. Due to its rarity, treatment is still directed by data mainly extrapolated from female breast cancer (FBC) treatment, despite the fact that it has recently become clear that MBC has its own molecular characteristics. DDX3 is a RNA helicase with tumor suppressor and oncogenic potential that was described as a prognosticator in FBC and can be targeted by small molecule inhibitors of DDX3. The aim of this study was to evaluate if DDX3 is a useful prognosticator for MBC patients. Nuclear as well as cytoplasmic DDX3 expression was studied by immunohistochemistry in a Dutch retrospective cohort of 106 MBC patients. Differences in 10-year survival by DDX3 expression were analyzed using log-rank test. The association between clinicopathologic variables, DDX3 expression, and survival was tested in uni- and multivariate Cox-regression analysis. High cytoplasmic DDX3 was associated with high androgen receptor (AR) expression while low nuclear DDX3 was associated with negative lymph node status. Nuclear and cytoplasmic DDX3 were not associated with each other. In a univariate analysis, high cytoplasmic DDX3 (p = 0.045) was significantly associated with better 10-year overall survival. In multivariate analyses, cytoplasmic DDX3 had independent prognostic value (p = 0.017). In conclusion, cytoplasmic DDX3 expression seems to be a useful prognosticator in MBC, as high cytoplasmic DDX3 indicated better 10-year survival.

An audit of over 1000 breast cancer patients from a tertiary care center of Northern India.

BACKGROUND: Breast cancer is the commonest cancer among women. India along with United States and China collectively account for one third of the global burden. The present study reports the clinico-epidemiological data of our patient population. This may help in better understanding of the disease in our population and also form ground for conducting further breast cancer research in India. METHODS: The study was conducted at an apex teaching and medical research institution in India from September 2013 to April 2015 as a retrospective review of prospectively collected data of breast cancer patients. The socio-demographic characteristics, reproductive risk factors, clinical presentation, TNM staging and histopathological characteristics for breast cancer in these patients were recorded. The data was recorded on an Xcel spreadsheet and analyzed using IBM SPSS 21. RESULTS: The study comprised of 1310 breast cancer patients with males comprising 1.1%. The median age of presentation was 47 years, and menarche 14 years. Most of women were married and multiparous. More than half of the women were postmenopausal at presentation. All patients were symptomatic at presentation with median duration of symptom of 5 months and median lump size of 5 cm. Most common stage at presentation was Stage II and most common histopathology was Invasive ductal carcinoma. 61.9% tumors were hormone receptor positive. Triple negative cancers formed one third of all tumors. CONCLUSION: Breast cancer in the Indian scenario is a disease of younger woman who lack the characteristic reproductive and demographic risk factors. This calls for a need to study the clinico-demographic risk factors and characteristics of our own population.

Factors associated with physical activity of breast cancer patients participating in exercise intervention.

PURPOSE: Physical activity has been known to improve survival and quality of life of patients with breast cancer. To find factors associated with physical activity, we analyzed the dataset of the multicenter controlled trial of exercise intervention. METHODS: Three hundred fifty-six participants were assigned to two groups: "Smart After-Care" (smartphone application and pedometer were provided) or exercise education only. Physical activity was measured by International Physical Activity Questionnaire-Short Form (IPAQ-SF) at baseline and after 12 weeks. The association between physical activity and other clinical characteristics was analyzed. RESULTS: At baseline, physical activity amount was 2315.5 ± 3513.2 MET min/week: 33.0% inactive, 49.6% minimally active, and 17.4% health-enhancing physical activity (HEPA) active. Factors associated with HEPA include cancer stage and grip strength. A significantly lower proportion was HEPA active among those with advanced stage than among those with stage 0. After intervention, physical activity was increased to 3466.2 ± 4712.5 MET min/week: 15.3% inactive, 50.4% minimally active, and 34.2% HEPA active. Physical activity was increased in 63.4% of the participants. Factors associated with physical activity increase include cancer stage, diarrhea, and type of exercise intervention. Participants with advanced stage have a 3.3 times higher chance of increasing physical activity. Participants who received "Smart After-Care" have a 64% higher chance of increasing physical activity. CONCLUSION: Before the intervention, participants with advanced stage are less likely to be HEPA active. Exercise intervention was more beneficial for those with advanced stage or physical symptoms. "Smart After-Care" was more effective than education only in increasing physical activity.

Dachshund 1 is Differentially Expressed Between Male and Female Breast Cancer: A Matched Case-Control Study of Clinical Characteristics and Prognosis.

INTRODUCTION: Male breast cancer (MBC) is rare and little is known about its biological behavior. In this study we described clinical characteristics and prognosis of MBC and evaluated roles of different factors between MBC and female breast cancer (FBC). PATIENTS AND METHODS: We retrospectively reviewed 42 MBC patients matched with 84 consecutive FBC patients with similar year, age, tumor, node, metastases (TNM) stage, and estrogen receptor (ER) expression from 2003 to 2016. Their clinical characteristics, treatments, and prognosis were analyzed, and immunohistochemistry for androgen receptor (AR), dachshund 1 (DACH1), sine oculis 1 (SIX1), eyes absent 1, B-cell lymphoma-2, and p53 were performed on paraffin sections. RESULTS: MBC constituted 0.56% (42 of 7561) of consecutive breast cancer and had a median age of 55 years. The 14 paraffin samples from men and 28 from women expressed all the assessed proteins, and DACH1 was significantly higher in women (P = .043). Body mass index (P = .023) and DACH1 (P = .034) were correlated with MBC prognosis, whereas the expression of AR (P = .049), SIX1 (P = .048), surgery (P < .001), and chemotherapy (P = .001) were important for FBC in addition to already known factors: tumor size and location, TNM stage (lymph nodes and organ metastasis), radiotherapy, and ER and human epidermalgrowth factor receptor-2 (HER2) expression. No distinct difference in recurrence was observed between MBC and FBC (P = .667). CONCLUSION: In this study we found that DACH1 was expressed less in MBC and HER2 was expressed more in FBC. They were respectively correlated with MBC and FBC prognosis. Although no significant differences were observed between MBC and FBC prognosis, DACH1, SIX1, and AR expression requires greater attention to develop treatment strategies for MBC and FBC.

Provider perspectives on barriers and facilitators to adjuvant endocrine therapy-related symptom management.

PURPOSE: Adjuvant endocrine therapy (AET) utilization is linked to improved clinical outcomes among breast cancer survivors (BCS); yet, AET adherence rates remain suboptimal. Little is known about provider perspectives regarding barriers and facilitators to AET-related symptom management (SM). In this study, we examined provider perspectives on the barriers and facilitators to AET-related SM among BCS and opportunities for improvement. METHODS: We conducted three focus groups (FGs) with a multidisciplinary group of healthcare providers (n = 13) experienced in caring for BCS undergoing AET. We utilized semi-structured discussion guides to elicit provider perspectives on AET-related SM. FGs were audiotaped, transcribed, and analyzed using qualitative software to identify key themes. RESULTS: Providers described patient-, provider-, and system-level barriers and facilitators to AET-related SM. At the patient-level, barriers included competing demands, limited time/resources, and possible misattribution of some symptoms to AET, while family/social relationships and insurance emerged as important facilitators. Discomfort with SM, limited time, and challenges distinguishing AET-related symptoms from other conditions were key provider-level barriers. Provider-level facilitators included routine symptom documentation and strong provider relationships. Care fragmentation and complexity of the cancer care delivery system were described as system-level barriers; however, survivor clinics were endorsed by providers. CONCLUSIONS: Provider perspectives on AET-related SM can shed light on SM barriers and facilitators spanning multiple levels of the cancer care delivery system. Strategies for improving AET-related SM in BCS include increasing patients' knowledge and engagement in SM, equipping providers with efficient SM strategies, and improving coordination of symptom-related services through survivorship programs.

CE: Late and Long-Term Sequelae of Breast Cancer Treatment.

: More than 12% of women will be diagnosed with breast cancer at some point in their lives, and 78% of them can be expected to survive for at least 15 years. More than 2.8 million breast cancer survivors currently reside in the United States. After breast cancer treatment, as many as 90% of survivors report physical problems that can reduce functional ability, produce or exacerbate emotional problems, negatively affect body image, and diminish quality of life. Many survivors will seek care for late and long-term effects of treatment, which will not necessarily be recognized as such by health care providers and appropriately treated. In this article, the authors discuss the underlying causes of late and long-term sequelae of breast cancer treatment and describe effective assessment and management strategies. They focus specifically on the most common and potentially debilitating upper body effects of breast cancer surgery and external radiation therapy: lymphedema, axillary web syndrome, postmastectomy pain syndrome, rotator cuff syndrome, adhesive capsulitis, arthralgias, cervical radiculopathy, and brachial plexopathy.

Prolactin and breast cancer: The need to avoid undertreatment of serious psychiatric illnesses in breast cancer patients: A review.

Hyperprolactinemia, defined as a sustained elevation of prolactin (PRL) levels greater than 530 mIU/L in women and greater than 424 mIU/L in men, has been implicated for a long time in breast cancer etiology and prognosis. Elevated PRL values (approximately 2-3 times higher than the reference values) are a common adverse effect of antipsychotic medications, especially with first-generation drugs, and most antipsychotics carry a standard warning regarding PRL elevations on their US product labels. These associations foster undertreatment of serious psychiatric illnesses in both otherwise healthy patients and cancer patients. This review assesses both the preclinical and clinical evidence that has led to the hypothesis of PRL's role in breast cancer risk or breast cancer progression. It is concluded that taken together, the published data are unconvincing and insufficient to deprive cancer patients in general and breast cancer patients specifically of potentially effective antipsychotic or antidepressant medications for serious psychiatric indications. We thus call on revised medication guidelines to avoid the existing undertreatment of serious psychiatric illnesses among cancer patients based on an unproven contraindication to psychiatric medications. Cancer 2016;122:184-188. © 2015 American Cancer Society.

Aromatase inhibitors for metastatic male breast cancer: molecular, endocrine, and clinical considerations.

Male breast cancer is a rare condition. Aromatase inhibitors are widely used for treating metastatic male breast cancer patients. In this setting, their use is not substantiated by prospective clinical trials, but is rather driven by similarities supposedly existing with breast cancer in postmenopausal women. This oversimplified approach was questioned by studies addressing the molecular and endocrine roots of the disease. In this manuscript, we discuss relevant aspects of the current use of aromatase inhibitors in metastatic male breast cancer in light of the most updated evidence on the molecular landscape of the disease and the specific changes in the hormonal background occurring with aging. We further point to strategies for blocking multiple hormonal pathway nodes with the goal of improving their therapeutic potential. We searched PubMed from its inception until March 2014 for relevant literature on the use of aromatase inhibitors in metastatic male breast cancer. Selected terms were combined and used both as medical headings and text words. The reference list of the suitable manuscripts was inspected for further publications. Aromatase inhibitors represent the mainstay of treatment in the metastatic setting. Yet, efforts aimed at sharpening the therapeutic potential of aromatase inhibitors still pose a challenge due to the paucity of data. The choice of dual hormonal (or sequential) therapy combining aromatase inhibitors with a GnRH analogue may represent a valid alterative, particularly if informed by cancer- and patient-related features including molecular, endocrine, and clinic characteristics.

The landscape of candidate driver genes differs between male and female breast cancer.

The rapidly growing collection of diverse genome-scale data from multiple tumor types sheds light on various aspects of the underlying tumor biology. With the objective to identify genes of importance for breast tumorigenesis in men and to enable comparisons with genes important for breast cancer development in women, we applied the computational framework COpy Number and EXpression In Cancer (CONEXIC) to detect candidate driver genes among all altered passenger genes. Unique to this approach is that each driver gene is associated with several gene modules that are believed to be altered by the driver. Thirty candidate drivers were found in the male breast cancers and 67 in the female breast cancers. We identified many known drivers of breast cancer and other types of cancer, in the female dataset (e.g. GATA3, CCNE1, GRB7, CDK4). In contrast, only three known cancer genes were found among male breast cancers; MAP2K4, LHP, and ZNF217. Many of the candidate drivers identified are known to be involved in processes associated with tumorigenesis, including proliferation, invasion and differentiation. One of the modules identified in male breast cancer was regulated by THY1, a gene involved in invasion and related to epithelial-mesenchymal transition. Furthermore, men with THY1 positive breast cancers had significantly inferior survival. THY1 may thus be a promising novel prognostic marker for male breast cancer. Another module identified among male breast cancers, regulated by SPAG5, was closely associated with proliferation. Our data indicate that male and female breast cancers display highly different landscapes of candidate driver genes, as only a few genes were found in common between the two. Consequently, the pathobiology of male breast cancer may differ from that of female breast cancer and can be associated with differences in prognosis; men diagnosed with breast cancer may consequently require different management and treatment strategies than women.

Secretory breast carcinoma: unique, triple-negative carcinoma with a favorable prognosis and characteristic molecular expression.

Secretory carcinoma is a rare but distinct subtype of breast carcinoma, with characteristic histomorphology and generally favorable prognosis. Although it was originally described as a juvenile breast carcinoma, occurring in young children, most cases have been reported in adults of both sexes. As the name implies, the characteristic histomorphology is the presence of a large amount of intracellular and extracellular, eosinophilic secretion material that stains positive for periodic acid-Schiff. Most tumors stain positive for S100 and negative for estrogen receptor, progesterone receptor, and ERBB2 (formerly HER2/neu) (ie, triple negative). In addition, some secretory carcinomas demonstrate a basal-like immunoprofile. Recent studies have shown the characteristic molecular feature: a balanced translocation t(12;15), resulting in an ETS variant 6-neurotrophic tyrosine kinase receptor type 3 (ETV6-NTRK3) fusion gene encoding a chimeric tyrosine kinase. Although rare events of axillary lymph node or distant metastases have been documented, the prognosis is generally excellent. The methods of surgical treatment and the role of adjuvant therapy, particularly for young patients, remain controversial.

Similarities and differences in the characteristics and primary treatment of breast cancer in men and women - a population based study (Sweden).

PURPOSE: Male breast cancer (MBC) is an uncommon disease. In the absence of randomized studies, current guidelines are mainly based on data on the management of female breast cancer (FBC). In light of concerns regarding the quality and extent of management in men, the aim of the present study was to investigate whether there are differences in tumor characteristics, treatment and outcome in male compared with FBC patients. METHODS: Cohorts of male and female breast cancer were retrospectively analyzed. All male patients diagnosed with invasive breast cancer between 1993 and 2007 were identified from the Regional Breast Cancer Register of the Uppsala-Örebro Region in Sweden. To increase the power of the study and obtain comparable cohorts we sampled four FBC patients (n = 396) for each MBC patient (n = 99) with similar age at diagnosis and time of diagnosis. RESULTS: No differences were seen in stage at diagnosis between MBC and FBC. Men underwent mastectomy more often than women (92% vs. 44%, p < 0.001). Radiotherapy was delivered less often to MBC than FBC (44% vs. 56%, p = 0.034), but radiotherapy given after mastectomy (44% vs. 39%, p = 0.47) did not differ between the groups. No differences were found regarding adjuvant chemotherapy (16% vs. 21%; p = 0.31) or adjuvant endocrine therapy (59% vs. 52%, p = 0.24). Both overall survival (41% vs. 55%, p = 0.001) and relative survival (74% vs. 88%, p = 0.015) were inferior in MBC compared to FBC. CONCLUSION: Concerns regarding less extensive treatment in MBC patients were not supported by this study. Although no differences in the stage of the disease or treatment intensity could be demonstrated, outcome was inferior in the male group.

Spectrum of disease in the male breast.

OBJECTIVE: The purpose of this article is to review the anatomy of the male breast and to describe the imaging findings of a variety of diseases that affect the male breast to better understand and recognize the imaging findings and underlying pathophysiology of diseases and conditions affecting this emerging subset of patients. CONCLUSION: Understanding the anatomy of the male breast is central to developing a differential diagnosis and delivering optimal care in male patients presenting with breast complaints. Diseases in the male breast can affect the skin and subcutaneous tissues, stroma and glandular elements, and neurovascular and lymphatic structures. Although the most commonly encountered disease entity is gynecomastia, men can develop many other benign and neoplastic diseases, including primary breast cancer. By incorporating clinical presentation with imaging findings on mammography and ultrasound, the breast imager can more effectively establish the correct diagnosis in males.

Breast cancer in men.

Less than 1% of all breast cancers occur in men, and although the disease is rare, the incidence appears to be increasing. Because men usually do not suspect breast cancer when they feel a lump in the breast, diagnosis frequently is delayed. Although screening for breast cancer is not recommended for men, radiographic imaging plays an important role in distinguishing benign conditions from malignant disease, and mammography usually is recommended as the first radiographic assessment. Ultrasonography is useful in differentiating between noncancerous cysts and solid malignant tumors, especially if coexisting gynecomastia masks a cancerous lesion on mammography. Sonography also is useful to guide breast biopsy.

Câncer de mama em homem: relato de caso e revisão da literatura / Male breast cancer: a case report and review of the literature

O câncer de mama em homens é uma patologia relativamente incomum. Atinge um homem para cada 1.000 mulheres, representa menos de 1 por cento de todos os cânceres em homens e é responsável por 0,1 por cento da mortalidade por câncer no sexo masculino. Como nas mulheres, o subtipo mais comum é o ductal infiltrativo. No presente trabalho é relatado o caso de um paciente masculino, 67 anos, com nódulo em mama direita com diagnóstico de carcinoma ductal sólido. Apesar de ser incomum, alguns estudos vêm demonstrando um aumento na incidência desses tumores. O exame físico talvez seja a principal ferramenta para o diagnóstico desse tumor. Contudo, a confirmação histopatológica é necessária para avaliação definitiva. Devido à raridade da doença, muitas das atuais modalidades de tratamento são baseadas na experiência com câncer de mama feminino. Este caso evidencia a relevância da conscientização da população sobre essa patologia e ao profissional da saúde em considerar este diagnóstico possível.

Male breast cancer is a fairly uncommon disorder. Affecting only one for a thousand women, it represents less than 1 percent of all male cancers and accounts for 0.1 percent of the male cancer mortality. Just like in women, the most common subtype is the infiltrative ductal. Here we report the case of a 67-year-old male patient with a nodule in the right breast with a diagnosis of solid ductal carcinoma. Although uncommon, a few studies show an increase in the incidence of this tumor. However, histopathologic confirmation is necessary for a definite evaluation. Due to the rarity of the disease, many of the current treatment modalities are based on the experience with female cancer. This case highlights the relevance of raising the awareness of the disease among the general population and health professionals in considering this a potential diagnosis.

Breast cancer in a male with ankylosing spondylitis treated with TNFalpha antagonists.

A 72-year-old male with a 4-year history of TNFalpha antagonist therapy (infliximab and etanercept) for ankylosing spondylitis was diagnosed with breast cancer. He had a family history of breast cancer. The low incidence and considerable severity of breast cancer in males, genetic risk factors, and potential role for TNFalpha antagonist therapy are discussed.

Breast cancer risk in patients with breast pain in Accra, Ghana.

OBJECTIVE: To determine the risk of breast cancer in patients presenting with breast pain in Accra, Ghana. DESIGN: Retrospective clinical study. SETTING: A self-referral breast clinic in Accra, Ghana. SUBJECTS: Patients with breast pain as a presenting complaint, between January 2001 and December 2005. INTERVENTIONS: Patients were investigated by triple assessment. RESULTS: There were 447 patients with pain, 322 as the only symptom and 125 in addition to other symptoms like breast lump and nipple discharge. Patients with pain only were found to have no detectable abnormality 203 (63%) and fibroadenosis 78 (24.2%) as the most common diagnoses. Breast cancer was found in four (1.24%) of them, all of whom had abnormality on clinical breast examination. In patients with pain as well as other symptoms the common diagnoses were fibroadenosis 25 (20%), breast cancer 20 (16%) and normal 18 (14.4%). CONCLUSION: The risk of breast cancer is significantly higher in patients presenting with breast pain in addition to other symptoms, compared to patients with breast pain as the only symptom (16% and 1.24% respectively P < 0.0001). Patients with breast pain should always have breast examination and not simply reassured. Women should be encouraged to do breast self examination.

Male breast malignancy in Jos University Teaching Hospital.

BACKGROUND: Male breast malignancies are rare. Cancer of the male breast accounts for about 1% of all breast cancers. Poor level of awareness often results in late presentation and delayed diagnosis in our environment. PATIENTS AND METHODS: A retrospective study of all cases of male breast cancer (MBC) managed in Jos University Teaching Hospital over a 17-year period (January 1987-December 2003.) RESULTS: A total of 302 cases of breast malignancies were managed over the study period. Twenty-six (8.6%) of these were males giving a male:female ratio of 1:10.6. The ages of the 26 MBC cases ranged from 12 years to 85 years, with a mean of 57.9 years and median age of 67 years. The right breast was affected in 15 and the left in 11. Mean duration of symptoms before presentation was 6 months with a range of 3 months to 4 years. All the patients had history of breast lumps, 21 (80.8%) of which were painless. Skin ulceration and axillary node enlargement were present in 19(73.1%) and 24(92.3%) respectively. Five (19.2%) were stage II; 15(57.7%) stage III and 6(23.1%) stage IV. There were 23 (88.5%) carcinomas, 2 (7.7%) fibrosarcomas and a case of Hodgkin's lymphoma. Invasive ductal carcinoma was the most common histological type in 20 (76.9%) of all breast malignancy and 20 (87.0%) of all breast carcinomas. Modified radical mastectomy (mastectomy with axillary clearance with or without division of the pectoralis minor muscle) was done in 10(38.5%) patients. Two of these were fibrosarcomas. Simple mastectomy was done in 13 (50%) as toilet procedures for advanced disease. The only case of Hodgkin's lymphoma had chemotherapy. Bilateral orchidectomy (BO), Tamoxifen, chemotherapy and radiotherapy were offered in 7(26.9%), 13(50%), 17(65.4%) and 7(26.9%) patients respectively. Wound infection was the most common complication in 14(53.8%) patients. There was no case of hospital mortality. CONCLUSION: MBC accounts for 8.6% of all breast cancers in our centre. It affects elderly males. Late presentation with advanced disease and ulceration is a common feature in our environment.