A review of the diagnosis and management of male breast cancer

Male breast cancer is an uncommon disease although the incidence has increased over the past 25 years. As with many other rare "orphan" diseases, male breast cancer is understudied. The rarity of the disease precludes prospective randomized clinical trials. In addition, few researchers and minimal funding have focused on breast cancer in men, but further work is clearly needed to better understand this disease. It shares many similarities with breast cancer in women; yet some clear differences have emerged. In this article, the latest information on the epidemiology, biology, and treatment of male breast cancer is reviewed.     

A systematic literature review of the management,oncological outcomes and psychosocial implications of male breast cancer

BackgroundAlthough male breast cancer (MBC) is a rare disease, accounting for <1% of all breast cancers, it has significant oncological, survival and psychosocial implications for patients. The aim of this study is to assess the latest literature in the diagnosis, management, oncological outcomes, and psychosocial impact of MBC.MethodsA systematic literature review was conducted using the PRISMA guidelines (Moher et al., 2009) [1] to explore the management of MBC, with particular focus on investigative imaging, surgical management, oncological outcomes, survival, genetic screening and psychosocial effects. Electronic databases were searched for randomised control trials, cohort studies and case series involving more than 10 patients. Imaging and surgical techniques, local and distant disease recurrence, survival, genetic screening and psychosocial implications in the setting of MBC were assessed.ResultsThe search criteria identified 199 articles, of which 59 met the inclusion criteria. This included 39,529 patients, with a mean age of 64.5 years (55–71), and a mean follow-up of 66.3 months (26.2–115). Mastectomy remains the most frequently used surgical technique, with an average of 89.6%. Loco-regional and distant recurrence rate was 10.1% and 21.4% respectively. Disease-free survival (DFS) at 5 and 10 years was 66.8% and 54.5% respectively. Disease-specific survival (DSS) at 5 and 10 years was 87.1% and 67.1% respectively. Overall survival (OS) at 5 and 10 years was 72.7% and 50.7% respectively. Genetic screening was conducted in 38.6% of patients of which 4.8% and 15.8% were found to be BRCA1 and BRCA2 carriers respectively. Psychosocial studies were conducted mainly using questionnaire and interview-based methodology focusing primarily on awareness of breast cancer in men, support available and impact on gender identity.ConclusionsThis review demonstrates that men present with later stage disease with subsequent impact on survival outcomes. There remains a paucity of high-level evidence and prospective studies are required. There is a need for increasing awareness amongst the public and health care professionals in order to improve outcomes and reduce stigma associated with MBC.     

A preclinical and clinical review of aflibercept for the management of cancer

Aflibercept, also known as vascular endothelial growth factor (VEGF)-Trap, is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting not only all forms of VEGF-A, but also VEGF-B and placental growth factor. It inhibits VEGF-induced angiogenesis in preclinical models. In tumor models, aflibercept is associated with the reduction of tumor vasculature and size, and the inhibition of ascites formation. Clinical studies are investigating the use of aflibercept alone and in combination with other antineoplastic therapies for the treatment of various cancers. Phase I and II studies have provided proof of principle, and support the continuing clinical investigation of aflibercept. Results from the phase III study, VITAL, of aflibercept in the second-line setting in patients with advanced non-small cell lung cancer [NCT00532155] demonstrated efficacy in progression-free survival and overall objective response rate, but overall survival was not significantly improved. A full report awaits publication. The Phase III VANILLA trial in metastatic pancreatic cancer [NCT00574275] showed no improvement in overall survival. Most recently, the phase III VELOUR study [NCT00561470] of aflibercept plus FOLFIRI compared with placebo plus FOLFIRI in patients with metastatic colorectal cancer following failure of an oxaliplatin regimen showed significant improvements in overall survival, progression-free survival, and response rate and the complete results have been submitted to a peer-reviewed journal. This review summarizes preclinical and clinical data for aflibercept and discusses future directions and clinical trials for this agent.     

A systematic review of the prevalence and attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and cancers in the United States

OBJECTIVES: To describe prevalence and estimated attribution of human papillomavirus (HPV) types in U.S. cervical, vaginal, and vulvar precancers and cancers. METHODS: U.S. studies reporting HPV typing for cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), and vaginal intraepithelial neoplasia (VaIN) and/or invasive cancers of those sites were gathered from the PubMed database (http://www.ncbi.nlm.nih.gov/sites/entrez/). Selected studies had PCR testing data for > or =10 cases for a disease endpoint. Analytic methods augmented prior reviews of cervical disease with an updated and expanded analysis (including vulvar and vaginal disease), new selection criteria for specimens, and adjustment for histologic type, where possible, among pooled cancer cases. In addition, for analyses of estimated attribution of HPV types, we incorporated accounting methods for lesions infected with multiple HPV types. RESULTS: Data from 22 U.S. studies meeting review eligibility criteria were tabulated. Following adjustment for the presence of multiple HPV types in a single specimen, the top two HPV types contributing to disease were CIN 1 (HPV 16/66; 15.3%), CIN 2/3 (HPV 16/31; 61.9%), cervical cancer (HPV 16/18; 79.2%), VIN 1 (HPV 6/11; 41.7%), VIN 3 (HPV 16/18; 84.0%), vulvar cancer (HPV 16/33; 55.5%), VaIN 3 (HPV 16/18; 65.1%), and vaginal cancer (HPV 16/18; 72.7%). CONCLUSIONS: The HPV type distribution and proportion of cases testing positive for any HPV type were observed to vary among U.S. cervical, vulvar, and vaginal neoplasias and by grade of disease. Adjustment for the presence of multitype HPV infections can have an important effect on the estimated attribution of HPV types to disease, particularly for types other than HPV 16.     

Correlation of DNA ploidy, histopathology, stage and clinical outcome in gastric carcinoma.

The determination of nuclear DNA ploidy from paraffin-embedded specimens was performed by flow cytophotometry on 277 surgically resected primary gastric carcinomas to assess the relationship of various pathological findings and DNA content with survival. The preparation of samples was performed by a modification of Hedley's technique and the staining method of Vindelov. Eighty-nine (32%) carcinomas were DNA diploid, 69 (25%) were DNA tetraploid, and 119 (43%) were DNA aneuploid. DNA non-diploid patterns were significantly associated with macroscopic ulcerative appearance, location of the tumour in the proximal stomach, histological grade, and advanced stage of tumour. Patients with DNA non-diploid cancers, and specifically DNA aneuploid cancers, exhibited significantly poorer survival than patients with DNA diploid tumours. These data support the prognostic value of tumour DNA content in patients with resected gastric carcinoma.     

Understanding and management of male breast cancer: a critical review

Breast cancer is a rare disease in men representing nearly 1% of the total breast cancer cases worldwide. While treatments developed for women with breast cancer are often applied to treat men with breast cancer, however, lack of awareness of this disease leads to its detection at a later stage in men. This review discusses male breast cancer and draws comparisons with female breast cancer and discusses current treatments available to treat this disease. It is believed that this review shall provide concise and relevant information increasing the awareness of issues revolving around male breast cancer (MBC).     

Radiation enteritis in children. A retrospective review, clinicopathologic correlation, and dietary management.

The clinicopathologic features of radiation enteritis are reviewed in 44 children receiving whole abdominal radiation therapy between 1961-1972 at the Institut Gustave-Roussy. Five of 14 long-term survivors (36%) developed severe delayed radiation injury with small bowel obstruction, occurring within 2 months after completion of irradiation. All had previously had acute radiation reaction during therapy. Histologic appearance in the small bowel at the time of delayed radiation injury revealed severe villus blunting, lymphatic dilatation, and moderately dense inflammatory infiltrate. All patients with delayed radiation injury showed marked clinical improvement coincident with a fractionated low-residue, low-fat diet, free of gluten and free of milk and milk products. The abnormal small bowel roentgenographs and small bowel biopsies reverted to a normal appearance in association with the diet. No exacerbation of radiation enteritis has been seen following dietary therapy.     

Gross genomic aberrations in precancers: clinical implications of a long-term follow-up study in oral erythroplakias.

PURPOSE: Gross genomic aberrations are increasingly seen as a cause rather than a consequence of carcinogenesis. Carcinomas may be prevented by systemically acting agents when used in high-risk individuals. If gross genomic aberrations could be shown to be predictive markers in precancers, they could serve as a tool for identifying high-risk individuals to be included in chemopreventive trials. PATIENTS AND METHODS: To investigate the predictive power of gross genomic aberrations in several types of oral premalignancies, we analyzed 57 biopsies from oral erythroplakias of 37 patients, both histologically and for DNA content. DNA content was measured by high-resolution image cytometry, and distribution histograms of DNA content were generated and interpreted according to established protocols. The primary end point was cancer-free survival. RESULTS: Fifty-seven dysplastic oral red lesions from 37 patients were investigated. Forty-one lesions from 25 patients were classified with aberrant DNA content (DNA aneuploidy), of which 23 patients (92%) later developed an oral carcinoma (after a median observation time of 53 months; range, 29 to 79 months). Of 12 patients having altogether 16 lesions with normal DNA content, none developed a carcinoma (median observation time, 98 months; range, 23 to 163 months; P <.001). In multivariate analysis, DNA content was a significant prognostic factor (P <.001), whereas histologic grade, sex, use of tobacco, size and location of lesions, and the presence multiple of lesions were not. CONCLUSION: Gross genomic aberrations are highly predictive for the subsequent occurrence of carcinomas from a wide range of oral premalignancies.     

Hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management

Acute hyperleukocytic leukemias (AHL) are associated with a very high early mortality rate mostly due to respiratory failure or intracranial bleeding. The pathophysiological process leading to these complications is called leukostasis but the biological mechanisms underlying its development and progression remain unclear. Although traditionally related to "over-crowding" of leukemic blasts in the capillaries of the microcirculation, leukostasis is likely to result from direct endothelial cell damage. This damage is probably mediated by soluble cytokines released during the interaction between leukemic cells and vascular endothelium and by the subsequent migration of leukemic blasts in the perivascular space. Leukemic cell's ability to respond to chemotactic cytokines and their expression of specific adhesion molecules are probably more important in determining whether leukostasis will develop than the number of circulating blasts. This could explain why leukostasis does not develop in all patients with AHL. The identification of the adhesion molecules, cytokines and receptors mediating endothelial cell damage in AHL should become a priority if therapeutic improvements are desired. Leukapheresis is widely used but it is unclear whether it provides additional benefit to a simpler and less invasive intervention with allopurinol, hydroxyurea and intravenous fluids. Cranial irradiation is not generally recommended. Induction chemotherapy should be started without delay. It is hoped that specific pharmacological inhibitors of the interaction between leukemic cells and vascular endothelium will result in an improved outcome for this very high-risk population.     

Increasing incidence and changing histopathology of primary lung cancer in Japan. A review of 282 autopsied cases

A total of 282 autopsied cases of primary carcinoma of the lung were reviewed from 1950 to 1983 to determine the incidence of histologic types, sex and age distribution, and to compare the trends between Japan and the United States. There were 75 cases in Group A (1950-1964), 89 in Group B (1965-1974) and 118 in Group C (1975-1983). The overall incidence, 282 cases per 8546 autopsies, was 3.3%; the male-to-female sex ratio was 2.4:1, and the mean age was 62 +/- 11 years. Increases in incidence in men, women, and the total from Group A to C were all statistically significant (P less than 0.05). A predominance of adenocarcinoma over squamous cell carcinoma in all cases was apparent in all the groups, but the data showed a trend toward a reduction in the proportion of adenocarcinoma and increases in the proportion of squamous cell carcinoma and small cell carcinoma. In contrast, an increasing incidence of adenocarcinoma was reported in the USA.     

A case of a male gastric choriocarcinoma with massive mesenteric tumor and review of the literature on male choriocarcinoma

A 32-year-old man was admitted to our hospital, complaining of an abdominal mass. An operation disclosed a large tumor, the size of a child's head, in the mesenterium of the transverse colon, with a multiple liver metastasis. A tumor resection was performed and, histologically, the tumor was diagnosed as being a choriocarcinoma. Gynecomastia was not observed. The patient died 2 months after this operation in spite of chemotherapy. An autopsy disclosed metastatic choriocarcinomas in the lungs, the liver, the peritoneum, the stomach, the adrenal glands and in the lymph nodes. The testis was found to be normal by a serial histological examination. Primary advanced adenocarcinoma, which is histologically similar to a choriocarcinoma, was found in the stomach. This case was finally diagnosed as being a gastric adenocarcinoma which showed choriocarcinomatous differentiation at various metastatic sites.     

A study on the clinical profile and management of inverted Papilloma

Inverted Papilloma is a unique neoplasm characterized by its tendency to destroy bone, tendency to recur after incomplete removal and association with malignancy. The uncertainty of its clinical features and projected behaviour has resulted in an ill-defined approach to its management. This is a prospective study of 30 patients of Inverted Papilloma admitted at Regional Institute of Medical Sciences, Imphal between August 2001 to July 2003. In this study, meticulous attention is given to the clinical presentation and management in a series of 30 patients with inverted papilloma. A majority of patients were between 50–70 years (40%) with a mean age of 52.3 years. M: F Ratio=3.3:1. Commonest presenting symptoms were unilateral nasal obstruction (93.3%), nasal discharge (40%) and epistaxis (36.6%). 90% of the patients had signs of involvement of the nasal cavity with one or more sinuses and 46% showed bony erosion on C.T. Scan studies. Surgery was the treatment of choice in 90% of the cases.     

Cancer chemoprevention. A review of ongoing clinical studies

The mass of experimental data on various possibilities of inhibiting the carcinogenic process is growing rapidly. However, the biological complexity of carcinogenesis and the intrinsic limitations of the animal models make it often very difficult to identify the real potentially effective agents among the hundreds currently being proposed. In fact, more than 600 potentially chemopreventive agents have been identified and approximately 30 of them are presently being tested in humans. The great heterogeneity of these compounds (they belong to over 20 different classes of chemicals) might be a positive feature as it indicates that a variety of approaches is possible and that the options for selecting effective compounds will be numerous. In recent years, what could be called 'clinical chemoprevention' (that is controlled studies to evaluate in human subjects the efficacy of potentially chemopreventive agents) has developed considerably: according to American estimates 4 chemopreventive agents were tested clinically in 1981, 10 in 1985 and 18 in 1988. The number of reported preclinical investigations was 10 in 1985 and 75 in 1988. This rapid expansion has obviously led to some confusion in terminology and in the evaluation of primary results; at present there is still a need for further investigations to better define clinical chemoprevention and to differentiate it from chemotherapy.     

A clinical review of the investigation and management of carcinoma of unknown primary in a single cancer network

AimsCarcinoma of unknown primary (CUP) is a common encounter in oncological practice and represents 2.0–6.0% of all invasive malignancies. Evidence to support particular therapeutic strategies in this patient population is scarce, and empirical therapies are frequently derived from research on patients where the primary tumour site is known.Materials and methodsThis retrospective study reviewed the management of all patients recorded to have a diagnosis of CUP in a single cancer centre over a period of 12 months. Health records were reviewed documenting the CUP subtype, the investigations carried out both in the referring cancer unit and subsequently at the cancer centre and the recommended treatment (type and regimen), together with survival. The outcomes were examined in respect to a number of prognostic factors. Statistical tests were considered significant at P < 0.05.ResultsOne hundred and sixty-six patients were recorded to have a diagnosis of CUP, representing 3.7% of all referrals to the cancer centre. The median age of patients was 68 years (range 32–94 years), and 52.0% were women. The three most common CUP subgroups were CUP-liver/multiple sites (25.0%), CUP-bone (21.0%) and CUP-brain (16.0%). The remaining subgroups occurred at frequencies of less than 10% each. Histological confirmation was only obtained in 55.0% of cases. Even within a single subtype, 41 patients with CUP-liver/multiple sites underwent a total of 19 different investigations before any treatment being given. Forty-seven (28.0%) patients received radiotherapy, 30 (18.0%) received chemotherapy and 58 (35.0%) received supportive care alone. Nine different 5-fluorouracil-containing regimens were used in 11 patients treated with chemotherapy for CUP-liver. The overall median survival for all patients was 4.0 months. Survival was better in patients with a good performance status (0–1) and absent liver metastases (median survival 15.0 months; 95% confidence interval 8.0–22.1) and those who received chemotherapy (median survival 13.0 months; 95% confidence interval 7.4–18.6). Multivariate analysis confirmed female gender (P = 0.006), a good performance status (0/1) (P < 0.0001) and absent liver metastases (P = 0.002) as favourable prognostic indicators.ConclusionsThe appropriate management of patients with CUP is unclear and this study revealed a high degree of variation in clinical practice. This area is in urgent need of clinical research to ensure that the treatment of CUP is evidence based. Until such time, clinical recommendations are suggested for the investigation and treatment of such patients. Therapeutic progress will be facilitated by designating a clinical lead for CUP in each clinical network.     

The changing histopathology of lung cancer: a review of 1682 cases.

We have reviewed the histopathology of lung cancer patients seen over the past 13 years at RPMI. Assessment of this data indicates that adenocarcinoma is becoming progressively more prevalent as related to the other forms of lung cancer. Factors which in part may account for this increased prevalence are: 1) changes in criteria for reading histopathology of lung cancer, particularly since 1967; 2) the increased incidence of lung cancer among the female population who have a propensity for adenocarcinoma; and 3) occupational and environmental factors. In 1974 adenocarcinoma for the first time became the most prevalent type of lung cancer at RPMI. Whatever the reason, if our data are truly representative of a national trend, adenocarcinoma will soon become the most prevalent type of lung cancer in the United States. This fact may result in an increasing death rate since the present 18-month survival rate for adenocarcinoma is substantially less than for squamous cell carcinoma, which has in the past been the prevalent form of the disease. As the smoking habits of women more closely approximate those of men, we expect that the incidence and mortality of lung cancer will prove to be quite similar in both sexes.     

Male breast cancer: a review of clinical management

Aims Male breast cancer incidence is 1% of all breast cancers and is increasing. We aim to present an overview of male breast cancer with particular emphasis on clinical management. Methods Studies were identified by an online search of literature in the MEDLINE database till June 2006 followed by an extensive review of bibliographies. Results Increased risk factors include genetic predisposition as in BRCA2 families; testicular dysfunction due to chromosomal abnormality such as Klinefelter’s syndrome or environmental factors such as chronic heat exposure and radiation. Clinical assessment with biopsy is the hallmark of diagnosis. Earlier presentations are becoming commoner but there are wide geographical differences. Surgical treatment involves simple or modified radical mastectomy along with surgical assessment of the axilla, either via sentinel node biopsy in clinically node-negative disease or axillary sampling/clearance in node-positive disease. Reconstructions for restoring body image have been recently reported. Indications for adjuvant therapies are similar to that in women. For metastatic disease, tamoxifen is still the mainstay for oestrogen receptor positive disease. For oestrogen receptor negative disease, doxorubicin based chemotherapy regimens are used. In addition, the oft neglected psychological aspects of men having a “cancer of women” are increasingly being recognised. Conclusions There is, thus, need for further increasing awareness among men to reduce stigma associated with presentation of symptoms related to breast. This should be in addition to stressing to clinicians the ways of earlier detection and tailor-made “gender oriented” treatment of breast cancer in men.     

The clinical management of hepatocellular carcinoma in the United States,Europe, and Asia: A comprehensive and evidence‐based comparison and review

Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, represents 1 of the leading causes of cancer deaths in the world with an estimated 21,670 deaths in the United States in 2013. In contrast to other malignancies, there is an array of treatment options for HCC involving several specialties in the multidisciplinary care of the patient. Consequently, vast heterogeneity in management tendencies has been observed. The objective of this report was to review and compare guidelines on the management of HCC from the United States (National Comprehensive Cancer Network), Europe (European Association for the Study of the Liver‐European Organization for Research and Treatment of Cancer), and Asia (consensus statement from the 2009 Asian Oncology Summit). By and large, all 3 guidelines are similar, with some variance in surveillance and treatment allocation recommendations because of regional differences in disease and other variables (diagnosis, staging systems) secondary to the lack of a concrete, high level of evidence. In contrast to other cancers, the geographic differences in tumor biology and resources make it impractical to have a globally universal guideline for all patients with HCC. Recommendations from the 3 groups are influenced by geographic differences in the prevalence and biology of the disease (ie, areas of increased hepatitis B prevalence) and available resources (organ availability for transplantation, finances, and accessibility to treatment). It is important for both physicians and policy makers to include these considerations when treating patients with HCC as well when structuring policies and guidelines. Cancer 2014;120:2824–2838. © 2014 American Cancer Society.     

A central review of histopathology reports after breast cancer neoadjuvant chemotherapy in the neo-tango trial

Background:

Neo-tAnGo, a National Cancer Research Network (NCRN) multicentre randomised neoadjuvant chemotherapy trial in early breast cancer, enroled 831 patients in the United Kingdom. We report a central review of post-chemotherapy histopathology reports on the surgical specimens, to assess the presence and degree of response.

Methods:

A central independent two-reader review (EP and HME) of histopathology reports from post-treatment surgical specimens was performed. The quality and completeness of pathology reporting across all centres was assessed. The reviews included pathological response to chemotherapy (pathological complete response (pCR); minimal residual disease (MRD); and lesser degrees of response), laterality, the number of axillary metastases and axillary nodes, and the type of surgery. A consensus was reached after discussion.

Results:

In all, 825 surgical reports from 816 patients were available for review. Out of 4125 data items there were 347 discrepant results (8.4% of classifications), which involved 281 patients. These involved grading of breast response (169 but only 9 involving pCR vs MRD); laterality (6); presence of axillary metastasis (35); lymph node counts (108); and type of axillary surgery (29). Excluding cases with pCR, only 45% of reports included any comment regarding response in the breast and 30% in the axillary lymph nodes.

Conclusion:

We found considerable variability in the completeness of reporting of surgical specimens within this national neoadjuvant breast cancer trial. This highlights the need for consensus guidelines among trial groups on histopathology reporting, and the participation of histopathologists throughout the development and analysis of neoadjuvant trials.