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BACKGROUND: The overall survival of patients with localised osteosarcoma has dramatically improved with the introduction of multidrug chemotherapeutic regimens into the treatment paradigm. However, despite optimal treatment, all-cause mortality remains higher among osteosarcoma survivors than in the general population. The development of second malignant neoplasms contributes to this higher mortality rate. CASE SERIES: We present three cases of patients definitively treated for osteosarcoma who subsequently developed a second malignant neoplasm. The first case describes a 17-year-old female with osteosarcoma of her right femur treated with surgical resection and perioperative chemotherapy. Ten years later, she was diagnosed with metastatic HER2-positive breast cancer. Genetic testing identified a germline TP53 mutation, confirming the presence of Li-Fraumeni syndrome. The second case details an 18-year-old male with osteosarcoma of his right humerus treated with definitive resection and perioperative chemotherapy. He was diagnosed with appendiceal adenocarcinoma after presenting with acute abdominal pain 17 years later. The third case reviewed is of a 36-year-old male with osteosarcoma of his right femur treated with definitive resection and adjuvant chemotherapy. A diagnosis of leiomyosarcoma was made 7 years later following surveillance imaging. DISCUSSION: The risk of second malignant neoplasms in osteosarcoma may relate to previous oncological treatment, an inherited cancer predisposition syndrome or a spontaneous new neoplasm. Although screening for a second malignancy is not routinely recommended for osteosarcoma survivors, a high degree of clinical suspicion should be maintained during surveillance.
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Adenocarcinoma/diagnóstico , Neoplasias Ósseas/diagnóstico , Osteossarcoma/diagnóstico , Adolescente , Adulto , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante , Feminino , Fêmur/patologia , Humanos , Leiomiossarcoma/diagnóstico , Síndrome de Li-Fraumeni/diagnóstico , Masculino , Segunda Neoplasia Primária/patologiaRESUMO
BACKGROUND: Cancer in pregnancy is relatively rare, but the incidence is increasing. Several studies show that cytotoxic agents are safe to use in pregnancy from the second trimester onwards. AIMS: This study assesses the maternal and foetal outcomes of cancers diagnosed during pregnancy. In particular, it focuses on a subset of women who elected to defer systemic chemotherapy until after delivery. This study examines if all cancers need to be treated during pregnancy or if, in certain cases, treatment can be safely deferred until after full-term delivery. METHODS: This is a retrospective observational study of women diagnosed with cancer during pregnancy in an Irish cancer centre over a 27-year period. All women diagnosed with cancer during pregnancy who were referred to the medical oncology department for consideration of chemotherapy were included in this study. Medical and pharmacy records were extensively reviewed. RESULTS: Twenty-five women were diagnosed with cancer in pregnancy and referred to medical oncology for consideration of systemic chemotherapy. Sixteen women (64%) commenced chemotherapy during pregnancy, seven women (28%) did not receive chemotherapy while pregnant, but commenced treatment immediately after delivery, and two (8%) did not receive any systemic chemotherapy at all. Of the seven women who commenced chemotherapy after delivery, six (85.7%) were diagnosed before 30/40 gestation. There were three cases of Hodgkin's lymphoma, two breast cancers and one ovarian cancer. After a median follow-up of 12 years, all six mothers remain disease-free. CONCLUSIONS: This study identified a select cohort of patients that did not receive chemotherapy during pregnancy. There were no adverse outcomes to mothers due to delayed treatment.
Assuntos
Tratamento Farmacológico/métodos , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Adulto , Feminino , Humanos , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Resultado da Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
Patients with inflammatory bowel disease (IBD) have an increased risk of developing malignancy. The use of immunosuppressive therapies and tumour necrosis factor (TNF) inhibitors in these patients may provide a further risk for the development of malignancy. We report the clinical and pathological findings of a high grade osteosarcoma in a patient with Crohns disease receiving TNF inhibitor therapy. In this case, a 32-year old female presented with a painful right knee after receiving maintenance adalimumab for Crohns disease for a period of six years. There is a substantial hypothetical link between TNF inhibitor regimens such as adalimumab and an increased risk of malignancy. TNF inhibitor therapy should be ceased and chemotherapy and surgery is an effective combined modality approach in these patients. The role of TNF inhibitors in patients after cancer diagnosis is uncertain and further research is required to assess efficacy and safety.
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BACKGROUND: Chemotherapy in the multimodality treatment of osteosarcoma has improved survival. Reported outcomes on adult patients are limited. Poor necrosis rates post neoadjuvant chemotherapy (NAC) is considered an adverse prognostic factor and attempts have been made to improve survival in this group. PATIENTS AND METHODS: Adult and young adult patients diagnosed with osteosarcoma between January 1986 and August 2012 were retrospectively reviewed. Patients identified were stratified according to stage (localised or metastatic) and age (≤40 and >40 years). Event free survival (EFS) and overall survival (OS) outcomes were determined. In patients with localised disease ≤40 years, survival was assessed according to necrosis rates post NAC (<90 and ≥90%). NAC consisted of two cycles of methotrexate alternating with doxorubicin/cisplatin (MAP) followed by definitive surgery. Those with ≥90% tumour necrosis continued on MAP. Patients with <90% necrosis received ifosfamide and etoposide (IE) post operatively. RESULTS: A total of 108 patients were reviewed and 97 were included. Median age was 23 years (range 16-75) and 70% of patients were male. Five year EFS and OS across all groups was 57% and 63% respectively. Of the patients with localised disease (N = 81), 5-year overall survival (OS), with a median follow up of 7 years (2-26) was 70% (p < 0.0001). Patients aged 16-40 (N = 68) with localised osteosarcoma had a significantly improved 5-year OS (74%) compared to those >40 years (N = 13) (42%) (p = 0.004). Of the 68 patients with localised osteosarcoma ≤40 years, 62 were evaluated according to necrosis rates post MAP. In 33 patients who achieved ≥90% necrosis and continued MAP, 5-year OS was 82%. In 29 patients who had <90% tumour necrosis and received adjuvant IE, 5-year OS was 68% (p = 0.15). Multivariate analysis confirmed age and stage as prognostic factors but not poor necrosis rates in our treated population. CONCLUSIONS: Long-term survival outcomes in a predominantly adult Irish population are similar to large reported trials. Age and stage at diagnosis are prognostic. Postoperative ifosfamide/etoposide alone in patients with poor necrosis rates is a feasible regimen, but its role in the adjuvant setting remains uncertain.
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BACKGROUND: Primary bone lymphoma (PBL) is a rare condition and accounts for less than 2% of adult lymphomas and 3% of all primary bone malignancies. Because of the rarity of this disease, there is a lack of prospective randomised clinical trials and hence optimal treatment is uncertain. AIM: We report on our experience of treating PBL over 20 years. METHODS: Using our hospital database, we identified all patients with PBL, their treatment, and long-term follow-up. RESULTS: From January 1989 to July 2007, we identified 12 patients with PBL. Long extremity bones were the most common presenting sites. Multifocal disease was present in three cases. Treatment modalities included surgery, chemotherapy, and radiotherapy. Median follow-up was 8 years (range 0.5-18.5 years), and overall survival was 100%. CONCLUSIONS: Combined modality therapy, i.e. chemotherapy followed by radiotherapy, is the preferred treatment option unless adverse neurology or an unstable fracture presents first.
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Neoplasias Ósseas/epidemiologia , Linfoma/epidemiologia , Adulto , Idoso , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Irlanda/epidemiologia , Linfoma/patologia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.
Assuntos
Neoplasias da Mama Masculina/genética , Genes BRCA1 , Genes BRCA2 , Aconselhamento Genético , Testes Genéticos , Estresse Psicológico , Adulto , Idoso , Análise Mutacional de DNA , Saúde da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Linhagem , Valor Preditivo dos Testes , PrognósticoAssuntos
Antineoplásicos/efeitos adversos , Isquemia Encefálica/induzido quimicamente , Cisplatino/efeitos adversos , Trombose/induzido quimicamente , Doença Aguda , Adulto , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/uso terapêutico , Terapia Combinada , Feminino , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapiaAssuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Humanos , Neoplasias Pulmonares/cirurgiaRESUMO
AIM: To describe the radiological findings in primary liver lymphoma, which is a rare entity, presenting usually as a localized liver mass. MATERIALS AND METHODS: We reviewed retrospectively the imaging findings at presentation, of patients in whom a diagnosis of primary liver lymphoma was finally made histologically. The study period covered a 10-year period between January 1990 and December 1999. There were seven patients, all men, with a mean age of 49.6 years. Each patient presented with hepatobiliary disease without peripheral adenopathy. Imaging prior to diagnosis included ultrasonography (seven patients), computed tomography (seven patients) and magnetic resonance imaging (MRI) (two patients). Appearances during and after aggressive chemotherapy were reviewed. RESULTS: Imaging appearances were of either single or multiple liver lesions simulating liver metastases. On ultrasound all foci of primary hepatic lymphoma (PHL) were hypoechoic relative to normal liver. Computed tomography (CT) showed hypoattenuating lesions in all cases, and two cases showed rim enhancement following contrast administration. The MRI appearances were variable, and no pathognomonic feature of PHL was identified, so that histology was required in all patients to establish the diagnosis. CONCLUSIONS: This paper demonstrates the spectrum of findings encountered on various imaging modalities in PHL. We conclude that although PHL is a rare condition, it should always be considered in the differential diagnosis of liver metastases when no primary tumour is apparent.
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Neoplasias Hepáticas/diagnóstico , Linfoma não Hodgkin/diagnóstico , Adulto , Idoso , Meios de Contraste , Diagnóstico Diferencial , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Linfoma não Hodgkin/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , UltrassonografiaRESUMO
Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201-995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1-5. Although elevated plasma somatostatin levels may be detected in 14-15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [(111)In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Receptores de Somatostatina/metabolismo , Somatostatina/uso terapêutico , Humanos , Neoplasias Pulmonares/metabolismo , Cintilografia , Compostos Radiofarmacêuticos/uso terapêutico , Somatostatina/análogos & derivadosAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Humanos , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Período Pós-OperatórioRESUMO
Non-small cell lung cancer accounts for 75% to 80% of the approximately 180,000 new cases of lung cancer that will develop in the Unites States this year. At the time of diagnosis, only 30% to 40% of patients are candidates for curative resection. Even for these patients, the 5-year survival rate ranges from 30% to 70%, indicating that many of these "early stage" patients have micrometastatic disease at the time of initial diagnosis. The remaining approximately 60% of newly diagnosed patients have either locally advanced unresectable disease or stage IV metastatic disease, and the majority of these patients will die of progressive disease before the first anniversary of their diagnosis. Overall, the 5-year survival rate for all newly diagnosed patients with non-small cell lung cancer has improved over the past two decades from 5% to 10% in the United States.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Taxoides , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Docetaxel , Humanos , Paclitaxel/análogos & derivados , Paclitaxel/uso terapêutico , Topotecan/uso terapêutico , Vimblastina/análogos & derivados , Vimblastina/uso terapêutico , Vinorelbina , GencitabinaRESUMO
Small cell lung cancer (SCLC) accounts for 20% to 25% of all lung cancer cases in developing countries. The incidence of and mortality from SCLC continues to increase in these countries, especially in females. Small cell lung cancer is different from other lung cancer histologic types in that it has neuroendocrine features, grows more rapidly, spreads earlier, is more responsive to chemotherapy and radiotherapy, and has a lower cure rate. Because of the propensity to metastasize early, the lack of screening modalities, and the sensitivity to chemotherapy, the cornerstone of treatment is combination chemotherapy, which is indicated in all SCLC patients able to tolerate any therapy. Patients with extensive-stage SCLC generally receive combination chemotherapy alone. Most patients with limited-stage SCLC should be treated with combined modality therapy consisting of chemotherapy and chest radiotherapy. In the rare patient with stage I SCLC and no involved lymph nodes, surgical resection with chemotherapy provides a high rate of long-term survival. Several combinations are used routinely, including the two-drug combination of etoposide with cisplatin or carboplatin, which is used most frequently in the United States. There is no proven role for any type of maintenance therapy, for intensive chemotherapy, or for biological therapies. There have been no major advances in therapy in the last decade, although the recent advent of new active agents, including gemcitabine, provides hope for more effective therapies in future years. This report will review the past literature on SCLC therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Células Pequenas/mortalidade , Ensaios Clínicos como Assunto , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Taxa de SobrevidaRESUMO
This study reports on the frequency and disease association pattern of a number of gene rearrangements in a large panel of lymphoid tumours (n = 94). We detected the t(11;14) translocation, involving rearrangement of the BCL-1 locus, in 60% of mantle cell lymphomas. The BCL-2 gene, located at band 18q21, was rearranged in 42% of follicle centre lymphomas (FCL) and in 15% of diffuse large B-cell (DLBC) lymphomas. In this study, 80% of the c-MYC rearrangements were detected in aggressive diffuse lymphoma subsets but, interestingly, 9% of FCL showed involvement of t(8q24) translocation. In our study, rearrangements of the BCL-6 gene at band 3q27 were found in 31% of DLBC lymphomas. Interestingly, 50% of the BCL-6 rearrangement positive lymphoma cases had coexisting gene rearrangements involving all of the aforementioned gene loci. The molecular dissection of these genes will improve our understanding of the genesis of the diverse clinicopathological subtypes.
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Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Linfoma não Hodgkin/genética , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes , Fatores de Transcrição/genética , Genes myc , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6 , Translocação GenéticaRESUMO
Lung cancer remains a major epidemic problem worldwide. The majority of cases are associated with cigarette smoking and the number of people who smoke continues to increase. As a result, the number of lung cancer cases and deaths is expected to increase proportionately over the next decade. The majority of patients who develop lung cancer die of this disease. Non-small cell lung cancer (NSCLC) accounts for 75% of all new cases. The only hope for significant survival depends on surgical resection. At the time of initial presentation, unfortunately, the vast majority of patients are inoperable, either because of advanced disease or because of the presence of comorbid medical conditions such as coronary artery disease. For these reasons, the overall survival rates for patients with NSCLC range from 10% to 15%, figures that have not improved substantially for 20 years. The role of systemic chemotherapy in this population remains debatable for many physicians. Nevertheless, recent studies clearly demonstrate that effective systemic chemotherapy in selected patients can improve survival, quality of life, and performance status. Recently, newer cytotoxic agents, such as vinorelbine, gemcitabine, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), docetaxel, and the camptothecins, have demonstrated their activity in treating patients with NSCLC. When combined with other effective agents, response rates exceeding 50% have been achieved, with median survivals of more than 1 year. The use of these newer agents in combination with well-established agents holds promise for the role of systemic chemotherapy in the future management of patients with early or late-stage NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Metanálise como Assunto , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Resultado do TratamentoRESUMO
Somatostatin analogue scintigraphy represents a new technique employing radiolabelled peptides to detect specific receptor-bearing lesions. 111Indium diethylene-triaminopentaacetic acid-linked octreotide (111In-DTPA-D-Phe1-octreotide), also known as [111In]pentetreotide or OctreoScan, is now established in the management of patients with neueroendocrine gastrointestinal tract and pancreatic tumours, and has proved effective in localizing disease sites in lung, breast and medullary thyroid carcinomas, lymphomas, meningiomas and others. In these conditions (a) the imaging of all disease sites at a single sitting (in a proportion of patients) thereby making further investigations unnecessary, (b) the localization of otherwise unexpected metastatic deposits and (c) the detection of residual disease not found by other means suggest that [111In]pentetreotide may be a useful adjunct in the diagnostic evaluation of patients with somatostatin receptor-bearing tumours.
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Neoplasias/diagnóstico por imagem , Somatostatina/análogos & derivados , Neoplasias da Mama/diagnóstico por imagem , Carcinoma de Células Pequenas/diagnóstico por imagem , Antagonistas de Hormônios , Humanos , Radioisótopos de Índio , Neoplasias Pulmonares/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Cintilografia , Receptores de Somatostatina/análiseRESUMO
More than 200 human small cell lung cancer and non-small cell lung cancer cell lines were established over 15 years mainly by utilizing the serum-free, hormone and growth factor supplemented, defined media HITES and ACL4. Use of modified, established cell culture techniques such as the mechanical spillout method for the releasing of cell aggregates from tumor tissue, ficoll gradient centrifugation for the separation of tumor cells from erythrocytes and tissue debris, and an apparatue consisting of a platinum tubing attached to a suction flask for removal of spent medium have greatly contributed to the success in culturing tumor cells. Characterization of these lung cancer cell lines have extended our knowledge of lung cell biology. Studies elucidating the nutritional requirements of lung cancer cell growth may be helpful for the manipulation of these tumors in patients.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Técnicas de Cultura de Células/métodos , Neoplasias Pulmonares/patologia , Ascite/patologia , Medula Óssea/patologia , Técnicas de Cultura de Células/instrumentação , Meios de Cultura Livres de Soro , Humanos , National Institutes of Health (U.S.) , Derrame Pleural/patologia , Manejo de Espécimes , Células Tumorais Cultivadas , Estados UnidosRESUMO
We evaluated the prognostic value of tumor angiogenesis in node negative breast cancer (NNBC). Paraffin-embedded tissues from 87 patients with NNBC were immunostained for factor VIII-related antigen, using one tissue block representative of the invasive edge of the tumor. Sections were scanned at low power to identify "hotspots" of angiogenesis. Microvessel (MV) counts were performed at x200 magnification, using a grid eyepiece graticule. Within each hot spot, three fields (area of field = 0.22 mm2) were counted and averaged. The highest average for a hot spot and the highest single field value was recorded for each case. Patients were stratified into low and high MV groups and their survival compared. There were no differences in disease-free or overall survival between the two groups whether the highest average or the highest single value was used. Microvessel counts did not correlate with other prognostic features, ie, grade, size, estrogen receptor status, c-erb B-2 or accumulated P53 status. Because of the difficulty in assessing angiogenesis that is heterogenous throughout tumors, MV counting may not be suitable for clinical use as a prognostic factor in NNBC. This problem could be addressed in a prospective study involving more extensive tumor sampling.