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1.
Biomedicines ; 12(3)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38540206

RESUMO

Ten percent of patients with breast cancer, and probably somewhat more in patients with ovarian cancer, have inherited germline DNA mutations in the breast and ovarian cancer genes BRCA1 and BRCA2. In the remaining cases, the disease is caused by acquired somatic genetic and epigenetic alterations. Targeted therapeutic agents, such as poly ADP-ribose polymerases (PARP) inhibitors (PARPi), have emerged in treating cancers associated with germline BRCA mutations since 2014. The first PARPi was FDA-approved initially for ovarian cancer patients with germline BRCA mutations. Deleterious variants in the BRCA1/BRCA2 genes and homologous recombination deficiency status have been strong predictors of response to PARPi in a few solid tumors since then. However, the relevance of somatic BRCA mutations is less clear. Somatic BRCA-mutated tumors might also respond to this new class of therapeutics. Although the related literature is often controversial, recently published case reports and/or randomized studies demonstrated the effectiveness of PARPi in treating patients with somatic BRCA mutations. The aim of this review is to summarize the predictive role of somatic BRCA mutations and to provide further assistance for clinicians with the identification of patients who could potentially benefit from PARPi.

2.
Sci Rep ; 13(1): 12985, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563292

RESUMO

Type 2 diabetes mellitus (T2DM) is a progressive disease, which affects colorectal cancer (CRC) survival. However, data on the relationship between CRC survival and T2DM duration is scarce and controversial. A retrospective observational study was conducted. Sub-cohorts were created based on the duration of T2DM as follows, ≤ or > 5/10/15/20 years. 204 of the 817 (24.95%) included study participants had T2DM at any point of CRC. 160 of the 204 CRC + T2DM patients had detailed T2DM duration data. At the time of CRC diagnosis, 85, 50, 31, and 11 patients had T2DM for > 5/10/15/20 years, respectively, which increased to 110, 71, 45, and 17 during the course of the study. Despite constant glycated hemoglobin values throughout the study, shorter overall and disease-specific survival times were observed for the > 5/10/15 years cohorts and longitudinal survival modeling techniques confirmed the significant effect of T2DM duration in all cohorts. While in the first 3 years after CRC diagnosis, the best survival was found for the ≤ 5 years cohort, all diabetes cohorts had the same survival thereafter. T2DM duration affected CRC survival significantly, therefore, a closer follow-up of this sub-populations is suggested.


Assuntos
Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Fatores de Risco , Estudos Retrospectivos , Hemoglobinas Glicadas , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico
3.
Pathol Oncol Res ; 26(3): 1499-1510, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31446607

RESUMO

We aimed to analyze the expression of cell-cycle regulation markers - minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) - in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core biopsy samples obtained prior to neoadjuvant therapy were analyzed. Immunohistochemistry was performed to analyze the expression of MCM2, Ki-67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, the presence of tumor infiltrating lymphocytes (TIL), pathological tumor response rate to the neoadjuvant therapy and patient survival. All investigated markers showed higher expression in high grade and in triple negative tumors (p < 0.01 and p < 0.05, respectively). Hormone receptor negative tumors showed significantly higher expression of Ki-67 (p < 0.01), MCM2 (p < 0.01) and Cyclin A (p < 0.01) than hormone receptor positive ones. Tumors with increased TIL showed significantly higher Ki-67 expression (p = 0.04). Pattern analysis suggested that novel cell-cycle marker-based subgrouping reveals predictive and prognostic potential. Tumors with high MCM2, Cyclin A or PHH3 expression showed significantly higher rate of pathological complete remission. Tumors with early relapse (progression-free survival ≤2 years) and shortened overall survival also show a higher rate of proliferation. Our cell cycle marker (Ki-67, MCM2, Cyclin A, PHH3) based testing could identify tumors with worse prognosis, but with a favorable response to primary systemic therapy. The pattern of cell-cycle activity could also be useful for predicting early relapse, but our findings need to be further substantiated in larger patient cohorts.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/metabolismo , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/efeitos dos fármacos , Feminino , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Prognóstico
4.
Front Oncol ; 9: 1012, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737558

RESUMO

Background: Modulated electro-hyperthermia (mEHT) is a variation of the conventional hyperthermia which selectively targets the malignant cell membranes in order to heat the malignant tissue and sensitize the tissue to oncology treatments. Although widely applied, the formulation of guidelines for the use thereof is still in progress for many tumors. Aim: In this paper we review the literature on the effects of mEHT in cancer patients on local disease control and survival. Methodology: Our review on data presents the collected experience with capacitive hyperthermia treatments with the EHY-2000+ device (OncoTherm Ltd., Germany). A literature search was conducted in Pubmed and articles were grouped and discussed according to: trial type, animal studies, in vitro studies, and reviews. Search results from Conference Abstracts; Trial Registries; Thesis and Dissertations and the Oncothermia Journal were included in the discussions. Results: Modulated electro-hyperthermia is a safe form of hyperthermia which has shown to effectively sensitizes deep tumors, regardless of the thickness of the adipose layers. The technology has demonstrated equal benefits compared to other forms of hyperthermia for a variety of tumors. Given the effective heating ability to moderate temperatures, the improved tumor perfusion, and ability to increase drug absorption, mEHT is a safe and effective heating technology which can be easily applied to sensitize tumors which have demonstrated benefits with the addition of hyperthermia. Modulated electro-hyperthermia also appears to improve local control and survival rates and appears to induce an abscopal (systemic) response to ionizing radiation. Conclusion: Based on clinical studies, the method mEHT is a feasible hyperthermia technology for oncological applications. Concomitant utilization of mEHT is supported by the preclinical and clinical data.

5.
Neuropsychopharmacol Hung ; 20(3): 112-116, 2018 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-30459288

RESUMO

Over the past ten years, in oncology there is an increased interest in understanding the cognitive dysfunction caused by chemotherapy also known as chemobrain or chemofog. As a result of oncological therapies the number of survivors of malignant diseases has increased considerably, but the side effects also appear to be more prevalent and severe including persistent cognitive symptoms. Symptoms of chemobrain include memory impairment, loss of concentration, speech and psychomotor deceleration, attention and learning coordination problems, and disturbance of executive functions. The symptoms may be transient but are often long-lasting, the latter negatively affecting functionality and quality of life. Structural and functional imaging studies (MRI, fMRI, PET) and neuropsychological tests are not consistent in the diagnosis of chemobrain. Several factors are suspected leading to the appearance of symptoms, but the specific patomechanism is not yet known. Nutrition status, age, anemia, inflammatory cytokines, stress, and depression can all affect the quality of life and may be related to cognitive symptoms. Currently, there is no treatment strategy for preventing or alleviating cognitive impairement related to chemobrain, and several pharmacotherapies are under investigation. Results imply that understanding the patomechanism of chemobrain can also yield a deeper understanding of cognitive dysfunction associated with depression.


Assuntos
Encéfalo , Transtornos Cognitivos , Depressão , Humanos , Testes Neuropsicológicos , Qualidade de Vida , Sobreviventes
6.
J Surg Case Rep ; 2018(4): rjy041, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29657704

RESUMO

We report a case of a patient with triple synchronous primary malignancies (breast, colon, kidney) which has not been previously reported in the literature. A 70-year-old woman was diagnosed with invasive ductal carcinoma of the left breast with axillary lymph node metastasis. During the staging period, renal cell carcinoma on the left kidney and mucinous adenocarcinoma in the proximal colon were found. Since the breast tumour demonstrated favourable biology, aromatase inhibitor therapy had been started and simultaneous right colectomy and left nephrectomy was performed. Six months after the first diagnosis, left sector excision and axillary block dissection were performed. Adjuvant FEC chemotherapy was administered, followed by radiotherapy. During the 16-month follow-up period disease recurrence was not detected.

8.
Nat Commun ; 8: 14944, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28429735

RESUMO

Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common 'metastatic precursor'. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination.


Assuntos
Neoplasias da Mama/genética , Variações do Número de Cópias de DNA , Sequenciamento do Exoma/métodos , Mutação , Adulto , Idoso , Autopsia , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Células Clonais/metabolismo , Células Clonais/patologia , Progressão da Doença , Feminino , Heterogeneidade Genética , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Filogenia
9.
Diagn Pathol ; 12(1): 20, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28222768

RESUMO

BACKGROUND: Studies have partly demonstrated the clinical validity of Ki-67 as a predictive marker in the neoadjuvant setting, but the question of the best cut-off points as well as the importance of this marker as a prognostic factor in partial responder/non-responder groups remains uncertain. METHODS: One hundred twenty patients diagnosed with invasive breast cancer and treated with neoadjuvant chemotherapy (NAC) between 2002 and 2013 were retrospectively recruited to this study. The optimal cut-off value for Ki-67 labeling index (LI) to discriminate response to treatment was assessed by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier curve estimation, log-rank test and cox regression analysis were carried out to reveal the association between Ki-67 categories and survival (DMFS = Distant metastases-free survival, OS = Overall survival). RESULTS: Twenty three out of 120 patients (19.2%) achieved pathologic complete remission (pCR), whereas partial remission (pPR) and no response (pNR) to neoadjuvant chemotherapy (NAC) was detected in 60.8% and 20.0%, respectively. The distribution of subtypes showed a significant difference in pathological response groups (p < 0.001). Most of the TNBC cases were represented in pCR group. The most relevant cut-off value for the Ki-67 distinguishing pCR from pNR cases was 20% (p = 0.002). No significant threshold for Ki-67 was found regarding DMFS (p = 0.208). Considering OS, the optimal cut-off point occurred at 15% Ki-67 (p = 0.006). The pPR group represented a significant Ki-67 threshold at 30% regarding OS (p = 0.001). Ki-67 and pPR subgroups were not significantly associated (p = 0.653). For prognosis prediction, Ki-67 at 30% cut-off value (p = 0.040) furthermore subtype (p = 0.037) as well as pathological response (p = 0.044) were suitable to separate patients into good and unfavorable prognosis cohorts regarding OS. However, in multivariate analyses, only Ki-67 at 30% threshold (p = 0.029), and subtype (p = 0.008) were independently linked to OS. CONCLUSIONS: NAC is more efficient in tumors with at least 20% Ki-67 LI. Both Ki-67 LI and subtype showed a significant association with pathological response. Ki-67 LI represented independent prognostic potential to OS in our neoadjuvant patient cohort, while pathological response did not. Additionally, our data also suggest that if a tumor is non-responder to NAC, increased Ki-67 is a poor prognostic marker.


Assuntos
Neoplasias da Mama/patologia , Antígeno Ki-67/análise , Terapia Neoadjuvante , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Estudos de Coortes , Estudos Transversais , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos
10.
Breast Cancer ; 24(1): 137-146, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26979062

RESUMO

OBJECTIVES: (1) To predict pathological complete remission (pCR) and survival after primary systemic therapy (PST) in patients diagnosed with breast cancer by using two different PET/CT based scores: a simplified PERCIST-based PET/CT score (Method 1) and a combined PET/CT score supplemented with the morphological results of the RECIST system (Method 2) and (2) to assess the effect of different breast carcinoma subtypes on tumor response and its evaluation. METHODS: Eighty-eight patients were enrolled in the study who underwent PET/CT imaging before and after PST. PET/CTs were evaluated by changes in maximum Standardized Uptake Value (SUVmax) and tumor size. Method 1 and 2 were applied to predict pathological complete remission (pCR). Kaplan-Meier analyses for survival were performed. Classification into biological subtypes was performed based on the pre-therapeutic tumor characteristics. RESULTS: A total of 30/88 patients showed pCR (34.1 %). Comparing pCR/non-pCR patient groups, significant differences were detected by changes in SUVmax (p < 0.001) and tumor size (p < 0.001) regarding the primary breast lesions. To predict pCR, Method 2 had higher sensitivity (72.4 % vs. 44.8 %) and negative predictive value (57.9 % vs. 45.8 %) with lower false negativity rate (16 vs. 32) than Method 1. pCR rate was higher in Her2-positive and triple negative tumors. Despite the significant differences detected between the biological subtypes regarding changes in primary tumor SUVmax (p = 0.007) and size (p = 0.015), the subtypes only had significant impact on response evaluation with Method 2 and not with Method 1. In our study, neither clinical nor pathological CR were predictors of longer progression-free survival. CONCLUSIONS: Our results suggest that combined PET/CT criteria are more predictive of pCR. The effect of biological subtypes is significant on pCR rate as well as on the changes in FDG-uptake and morphological tumor response. Response evaluation with combined criteria was also able to reflect the differences between the biological behavior of breast tumor subtypes.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos Transversais , Intervalo Livre de Doença , Reações Falso-Negativas , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Mastectomia , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
11.
Croat Med J ; 57(2): 131-9, 2016 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-27106355

RESUMO

AIM: To identify breast cancer subtypes likely to respond to primary systemic therapy (PST or neoadjuvant therapy) and to assess the accuracy of physical examination (PE) and breast ultrasonography (US) in evaluating and predicting residual size of breast carcinoma following PST. METHODS: 116 patients who received at least two cycles of PST between 1998 and 2009 were selected from a prospectively collected clinical database. Radiological assessment was done by mammography and US. Prior to PST, tumors were subclassified according to core biopsy (NCB) and/or fine-needle aspiration-based immunohistochemical profiles of NCB. Pathological response rates were assessed following the surgeries by using Chevallier classification. Tumor measurements by PE and US were obtained before and after PST. Different clinical measurements were compared with histological findings. Disease-free survival (DFS) was assessed. RESULTS: Pathological complete remission (pCR=Chevallier I/II) was observed in 25 patients (21.5%), 44% of whom had triple negative histology, 28% Her2 positive and 76% had high-grade tumor. Of 116 patients, 24 received taxane-based PST, 48 combined taxane + anthracycline treatment, 8 trastuzumab combinations, 21 anthracycline-based treatments, and 15 other treatments. In the taxane treated group, the pCR rate was 30%, in the taxane + anthracycline group 25%, in the anthracycline group 9.5%, and in trastuzumab group 37.5%. After PST, PE and US were both significantly associated with pathology (P<0.001 and P=0.004, respectively). Concerning OS, significant difference was observed between the Chevallier III and IV group (P=0.031) in favor of Chevallier III group. In the pCR group, fewer events were observed during the follow-up period. CONCLUSIONS: Our results show that even limited, routinely used immunohistochemical profiling of tumors can predict the likelihood of pCR to PST: patients with triple negative and Her2-positive cancers are more likely to achieve pCR to PST. Also, PE is better correlated with pathological findings than US.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estadiamento de Neoplasias , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Valor Preditivo dos Testes , Receptor ErbB-2/metabolismo , Resultado do Tratamento , Ultrassonografia
12.
Virchows Arch ; 468(6): 675-86, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27026269

RESUMO

We aimed to analyze to what extent expression of four cell cycle regulation markers-minichromosome maintenance protein (MCM2), Ki-67, cyclin A, and phosphohistone-H3 (PHH3)-predict response to primary systemic therapy in terms of pathological complete remission (pCR). In search of an accurate and reproducible scoring method, we compared computer-assisted (CA) and routine visual assessment (VA) of immunoreactivity. We included 57 patients with breast cancer in the study. The cell cycle markers were detected using immunohistochemistry on pre-therapy core biopsy samples. Parallel CA (validated by manual labeling) and standard VA were performed and compared for diagnostic agreement and predictive value for pCR. CA and VA results were dichotomized based on receiver operating characteristic analysis defined optimal cut-off values. "High" was defined by staining scores above the optimal cut-off, while "low" had staining scores below the optimal cut-off. The CA method resulted in significantly lower values for Ki-67 and MCM2 compared to VA (mean difference, -3.939 and -4.323). Diagnostic agreement was highest for cyclin A and PHH3 (-0.586 and -0.666, respectively). Regardless of the method (CA/VA) used, all tested markers were predictive of pCR. Optimal cut-off-based dichotomization improved diagnostic agreement between the CA and VA methods for every marker, in particular for MCM2 (κ = 1, p < 0.000). Cyclin A displayed excellent agreement (κ = 0.925; p < 0.000), while Ki-67 and PHH3 showed good agreement (κ = 0.789, p < 0.000 and κ = 0.794, p < 0.000, respectively). We found all cell cycle markers (Ki-67, MCM2, cyclin A, and PHH3) predictive of pCR. Diagnostic agreement between CA and VA was better at lower staining scores but improved after optimal cut-off-based dichotomization.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiologia , Imuno-Histoquímica , Adulto , Idoso , Neoplasias da Mama/metabolismo , Feminino , Humanos , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade
13.
Anticancer Res ; 35(9): 5063-72, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26254408

RESUMO

BACKGROUND: Precise and standardized response evaluation enables clinicians to tailor primary systemic therapy (PST). PATIENTS AND METHODS: Breast cancer patients underwent (18)F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) before and after PST. Response was assessed by maximal Standardized Uptake Value (SUVmax); morphological changes and Ki-67 labeling index (LI). In parallel response assessment was performed by European Organization for Research and Treatment of Cancer (EORTC); PET Response Criteria in Solid Tumors (PERCIST); World Health Organization (WHO); Response Evaluation Criteria in Solid Tumors (RECIST); Chevallier and Sataloff classifications, and by a novel Ki-67 score. Accuracy of different scoring systems was evaluated. RESULTS: In the 42 enrolled patients, SUVmax, size, and Ki-67 LI decreased significantly on PST. Significant differences between patients with versus those without pathological complete response were observed for pre-treatment Ki-67 LI and SUVmax and for post-treatment Ki-67 LI, SUVmax and size. Change in Ki-67 LI was the best predictor of pathological complete response. Correlation patterns of the directly measured metabolic, morphological, and proliferation responses differed from those determined by scoring methods. CONCLUSION: During PST, FDG-PET/CT enables for robust assessment of treatment efficacy, but more reliable scoring systems are still needed for more precise response evaluation.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama Masculina/diagnóstico por imagem , Neoplasias da Mama Masculina/tratamento farmacológico , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROC , Cintilografia , Resultado do Tratamento , Carga Tumoral
14.
Croat Med J ; 56(2): 128-38, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25891872

RESUMO

AIM: To evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas.; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring. METHODS: 188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled. 26 patients received mostly taxane-based PST without trastuzumab (Group 1) and 17 patients received trastuzumab-containing PST (Group 2). We compared the concordance between pCR and complete remission (CR) defined by breast-ultrasound, CR defined by standard 18F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) criteria (Method 1) and CR defined by a novel, breast cancer specific FDG-PET/CT criteria (Method 2). Sensitivity (sens), specificity (spec), and positive (PPV) and negative predictive values (NPV) were calculated. RESULTS: Ten patients (38.5%) in Group 1 and eight (47%) in Group 2 achieved pCR. pCR was significantly more frequent in Her2-positive than in Luminal B/Her2-positive tumors in both Group 1: (P=0.043) and Group 2: (P=0.029). PET/CT evaluated by the breast cancer specific criteria (Method 2) differentiated pCR from non-pCR more accurately in both groups (Group 1: sens=77.8%, spec=%, PPV=100%, NPV=71.4%; Group 2: sens=87.5%, spec=62.5%, PPV=70%, NPV=83.3%) than standard PET/CT criteria (Method 1) (Group 1: sens=22.2% spec=100% PPV=100% NPV=41.7%; in Group 2: sens=37.5%, spec=87.5%, PPV=75% NPV=58.3%) or breast ultrasound (Group 1, sens=83.3% spec=25% PPV=62.5% NPV=50%; Group 2, sens=100% spec=12.5% PPV=41.6% NPV=100%). CONCLUSION: The benefit of targeted treatment with trastuzumab-containing PST in Her2 overexpressing breast cancer was defined in terms of pCR rate. Luminal B/Her2-positive subtype needs further subdivision to identify patients who would benefit from PST. Combined evaluation of tumor response by our novel, breast cancer specific FDG-PET/CT criteria accurately differentiated pCR from non-pCR patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Carboplatina/administração & dosagem , Estudos Transversais , Docetaxel , Feminino , Fluordesoxiglucose F18 , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Taxoides/administração & dosagem , Tomografia Computadorizada por Raios X , Trastuzumab
15.
Patient Educ Couns ; 98(6): 695-703, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25749023

RESUMO

OBJECTIVE: Primary systemic therapy (PST) followed by surgery is the standard initial treatment for locally advanced breast cancer (LABC). However, some patients are averse to mastectomy or breast-conserving surgery and do not consent to these procedures. The reasons for this controversial decision, the factors influencing the decision-making and optimal solutions for decision aiding need to be investigated. METHODS: We addressed these questions by a review of literature on the possibilities associated with different patient choices and subsequent treatment options in relation to LABC. RESULTS: A total of 5 reviews and 22 clinical studies were summarized in relation to decision making and the most successful decision aids. A discussion is given of the issues of those few patients who cannot be convinced to undergo surgery. CONCLUSION: Currently there is no guideline for the treatment of patients who reject the surgical procedures after PST. Medical oncologists should be able to apply decision aid modalities in a personalized manner to give all needed information to their patients thereby ensuring a deliberate decision-making process, facilitating acceptance of a need for surgery, and thus improving the chances of prolonged survival. PRACTICE IMPLICATIONS: Currently multidisciplinary tumor boards are the most suitable decision aids in oncological practice.


Assuntos
Neoplasias da Mama/terapia , Tomada de Decisões , Avaliação de Processos e Resultados em Cuidados de Saúde/tendências , Participação do Paciente , Adulto , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Técnicas de Apoio para a Decisão , Feminino , Humanos , Mastectomia
16.
World J Surg Oncol ; 11: 122, 2013 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-23721061

RESUMO

We report the first European case of cerebral iodized lipid embolism post transcatheter arterial embolization for hepatocellular carcinoma. Lipiodol emboli and corresponding multifocal brain ischemia were documented with computed tomography (CT) and magnetic resonance (MR) in the acutely symptomatic patient. Transcranial Doppler sonography with contrast indicated a right-to-left shunt, while on a follow-up CT scan lipiodol embolization was detected in both lungs. Dilated pulmonary vessels and thick vascular channels were seen in the vicinity of the right diaphragm suggestive of pulmonary arteriovenous shunt. The patient symptoms regressed with supportive care alone, but he died 5 months later due to hepatic failure unrelated to the procedure.


Assuntos
Derivação Arteriovenosa Cirúrgica , Carcinoma Hepatocelular/complicações , Embolização Terapêutica/efeitos adversos , Óleo Etiodado/administração & dosagem , Embolia Intracraniana/terapia , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Evolução Fatal , Humanos , Embolia Intracraniana/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade
17.
Orv Hetil ; 153(49): 1958-64, 2012 Dec 09.
Artigo em Húngaro | MEDLINE | ID: mdl-23204302

RESUMO

INTRODUCTION: FDG-PET-CT is highly sensitive in detection of viable tumour tissue, giving an importance for that in oncological diagnostics. AIM: The authors analysed retrospectively the relationship between metabolic response and changes in Ki-67, a proliferation marker. METHODS: Staging FDG-PET-CT scans (before and after therapy) SUVs (Standardized Uptake Value), and morphological changes in the primary tumour and axillary lymph node region were evaluated in 30 patients with breast cancer. Calculated ΔSUV were compared with Ki-67 proliferation marker (measured in biopsies and surgical specimens). RESULTS: The decrease of SUV and size were significant in the primary tumour and the axillary lymph node region. Decrease of Ki-67 was significant. Significant correlation was found between Ki-67 and SUV before therapy, initial Ki-67 and ΔSUV, and ΔKi-67 and ΔSUV. CONCLUSIONS: The metabolic changes were more sensitive in the measurement of the therapeutic response than morphological remission, and they correlated well with the pathological response, in not standardized clinical conditions even.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Meios de Contraste , Fluordesoxiglucose F18 , Linfonodos/patologia , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Idoso , Axila , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Meios de Contraste/metabolismo , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Linfonodos/diagnóstico por imagem , Metástase Linfática , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Indução de Remissão , Sensibilidade e Especificidade , Resultado do Tratamento
18.
Magy Onkol ; 56(2): 75-8, 2012 May.
Artigo em Húngaro | MEDLINE | ID: mdl-22629543

RESUMO

There is a reasonable heterogeneity in the morphological appearance and the immunohistochemical properties of distinct breast tumors. Furthermore, it is also known that cancer arising in young women have different prognosis than the ones developing in the elderly. We analyzed breast tumors of 41 young (<35 years) and 33 older women (>65 years) regarding histopathological properties and immunohistochemical reactions for ER, PgR, HER2 and Ki-67, as well as HER2 FISH. The longest diameters, thus largest available surface areas of the tumors were included in the evaluation. Different regions were marked for morphology and in all immunohistochemical reactions. The regions in the distinct tumors showing different pathological and immunohistochemical appearance were identical (p<0.001). The number of morphologically different tumor regions were more frequent in tumors developing in the young (1.82 vs. 1.48 regions/tumor), and 53.6% of tumors with heterogeneous architecture were in young vs. 39.4% in the elderly. However, regarding HER2 staining, cancers in the young patients have shown greater variability among the different tumor areas (p=0.007). The origin of tumor cells predicting prognosis remains undetermined. Whether the analysis of the expression pattern of the whole tumor is conducted or the minute regions are separately examined and averaged, the same results can be achieved. With the development of molecular techniques and accurate prognostic and treatment information rendered to samples the question may be soon answered.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Antígeno Ki-67/análise , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização in Situ Fluorescente , Prognóstico
19.
Orv Hetil ; 151(32): 1299-303, 2010 Aug 08.
Artigo em Húngaro | MEDLINE | ID: mdl-20656670

RESUMO

Pregnancy-associated breast cancer (PABC) is defined as cancer of the breast diagnosed during pregnancy and up to 1 year postpartum. The crude incidence is 1/3000 pregnant women. As women delay childbearing the incidence of PABC increases with age. Young patients with PABC do not have worse prognosis compared with those with non-PABC; however, pregnancy can contribute to a delay in breast cancer diagnosis, evaluation, and treatment. Primary care physicians and gynecologists should be careful in the thorough workup of breast symptoms in the pregnant population to expedite diagnosis and allow multidisciplinary treatment as early as possible following the established diagnosis. Authors report a case of a 30-year-old pregnant woman, who detected inflammatory signs of her right breast and a palpable axillary mass at the 21st week of gestation. Her symptoms did not improve with administration of antibiotics. Therefore fine needle aspiration biopsy of the axillary lump was performed, with the result of unequivocal diagnosis of metastatic invasive carcinoma. The patient was referred to the multidisciplinary tumor board of our Department at the 27st week of gestation with the symptoms of inflammatory breast cancer, palpable right axillary and supraclavicular lymph nodes. Core biopsy showed an ER and PR negative, Her-2 positive, grade 3, infiltrating ductal carcinoma of the breast. After multidisciplinary team consultation the patient declined any kind of therapy during her pregnancy. On the 30th week of gestation caesarean section was performed. The premature baby girl was treated in the Neonatal Intensive Care Unit. Imaging modalities revealed no evidence of distant metastases short after the delivery. After 6 cycles of chemotherapy (docetaxel-doxorubicin-cycclophosphamid) the patient underwent right mastectomy and axillary lymph node dissection. Complete pathological response was diagnosed, since no residual tumor was found in the surgical resection specimen. After radiotherapy, trastuzumab medication was initiated. To date, there is no evidence of local recurrence or distant metastases during her 24 months follow-up. The newborn is on close neurohabilitation follow-up due to the evidence of generalized muscle dystonia. Had the patient accepted chemotherapy, the damage of the newborn baby would have been avoidable.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Complicações Neoplásicas na Gravidez/terapia , Adulto , Fatores Etários , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Quimioterapia Adjuvante , Comportamento de Escolha , Feminino , Humanos , Inflamação , Comunicação Interdisciplinar , Metástase Linfática , Mastectomia/métodos , Terapia Neoadjuvante/métodos , Participação do Paciente , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Radioterapia Adjuvante , Resultado do Tratamento
20.
Magy Onkol ; 54(1): 19-26, 2010 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-20350864

RESUMO

The two far ends of the age at the diagnosis of breast cancer are the age of younger than 35, and that of older than 70. Most probably, these two groups of patients differ in many ways. The aim of our present study was to underline the fact that age at the diagnosis of breast cancer is indeed a prognostic factor. Between October 1995 and March 2009, 80 old and 51 young breast cancer patients were treated at the Department of Diagnostic Radiology and Oncotherapy, Semmelweis University, Budapest. The prognostic and predictive factors of the tumors were analysed together with the disease-free and overall survival data. There were statistically significant differences between the two groups concerning the menstrual and reproductive factors, histological characteristics and immunophenotype of the tumors. Tumor size, nodal status and the Nottingham Prognostic Index did not show statistically significant differences. A trend to a shorter disease-free survival, higher rate of distant metastases and disease-specific death was seen in the group of young patients, but it was not significant. Overall survival was significantly shorter in the group of young patients. Therefore, we can state that young patients have a more aggressive disease and worse outcome. There is an increased importance of self examination in these groups, since both age groups are beyond the age limits of the screening population in Hungary. The media and primary school education as well should be involved in educating women concerning this aspect. The individual follow-up of young patients with positive family history should also be established.


Assuntos
Envelhecimento , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Genes Supressores de Tumor , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Intervalo Livre de Doença , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Hungria/epidemiologia , Metástase Linfática , Mutação , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Reprodução , Fatores de Risco
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