RESUMO
Patients with cancer should appropriately receive antiemetic therapies against chemotherapy-induced nausea and vomiting (CINV). Antiemetic guidelines play an important role in managing CINV. Accordingly, the first Japanese antiemetic guideline published in 2010 by the Japan Society of Clinical Oncology (JSCO) has considerably aided Japanese medical staff in providing antiemetic therapies across chemotherapy clinics. With the yearly advancements in antiemetic therapies, the Japanese antiemetic guidelines require revisions according to published evidence regarding antiemetic management worldwide. A revised version of the first antiemetic guideline that considered several upcoming evidences had been published online in 2014 (version 1.2), in which several updated descriptions were included. The 2015 JSCO clinical practice guideline for antiemesis (version 2.0) (in Japanese) has addressed clinical antiemetic concerns and includes four major revisions regarding (1) changes in emetogenic risk categorization for anti-cancer agents, (2) olanzapine usage as an antiemetic drug, (3) the steroid-sparing method, and (4) adverse drug reactions of antiemetic agents. We herein present an English update summary for the 2015 JSCO clinical practice guideline for antiemesis (version 2.0).
Assuntos
Antieméticos , Antineoplásicos , Neoplasias , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Humanos , Japão , Oncologia , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Vômito/induzido quimicamente , Vômito/tratamento farmacológicoRESUMO
BACKGROUND: Hypoxia is a key driver of cancer progression. We evaluated the prognostic impact of 18F-fluoromisonidazole (FMISO) prior to treatment in patients with breast cancer. METHODS: Forty-four patients with stage II/III primary breast cancer underwent positron emission tomography/computed with 18F-fluorodeoxyglucose (FDG-PET/CT) and FMISO. After measurement by FDG-PET/CT, the tissue-to-blood ratio (TBR) was obtained using FMISO-PET/CT. FMISO-TBR was compared for correlation with clinicopathological factors, disease-free survival (DFS), and overall survival (OS). Multiplex cytokines were analyzed for the correlation of FMISO-TBR. RESULTS: Tumors with higher nuclear grade and negativities of estrogen receptor (ER) and progesterone receptor had significantly higher FMISO-TBR than other tumors. Kaplan-Meier survival curves showed that patients with a higher FMISO-TBR (cutoff, 1.48) had a poorer prognosis of DFS (p = 0.0007) and OS (p = 0.04) than those with a lower FMISO-TBR. Multivariate analysis indicated that higher FMISO-TBR and ER negativity were independent predictors of shorter DFS (p = 0.01 and 0.03). Higher FMISO-TBR was associated with higher plasma levels of angiogenic hypoxic markers such as vascular endothelial growth factor, transforming growth factor-α, and interleukin 8. CONCLUSIONS: FMISO-PET/CT is useful for assessing the prognosis of patients with breast cancer, but it should be stratified by ER status. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000006802 . Registered on 1 December 2011.
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Neoplasias da Mama/diagnóstico por imagem , Misonidazol/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Adulto , Idoso , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/mortalidade , Hipóxia Celular , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Pessoa de Meia-Idade , Misonidazol/administração & dosagem , Prognóstico , Receptores de Estrogênio/metabolismoRESUMO
After the publication of this article [1], we noticed that in Fig. 2, the survival curve images (C and D, lower panel) were incorrect. The corrected Fig. 2 is presented below. The correction does not affect in any our results and conclusions.
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BACKGROUND: This phase II neoadjuvant study evaluated the efficacy and safety of a triweekly regimen of docetaxel and carboplatin in combination with trastuzumab (TCbH) in Japanese women with human epidermal growth factor receptor type2 (HER2)-positive primary breast cancer. METHODS: Patients with HER2-positive, stage I-III invasive breast cancer received six courses of trastuzumab (8 mg/kg loading dose, then 6 mg/kg, day 1), docetaxel (75 mg/m2, day 1), and carboplatin (area under the curve: 6, day 1) every 3 weeks. The primary endpoint was pathological complete response (pCR) of both breast and axillary lymph node disease. RESULTS: Fifty patients were enrolled in this study. Median age was 58 (range 32-75) years. All patients underwent definitive surgery. Thirty-three (66%) patients completed the chemotherapy course, while the treatment was delayed or discontinued in the other 17 (34%) patients because of adverse events (AEs). The pCR rate was 52%; the overall response rate was 66%. Grade 3/4 AEs due to nonhematological toxicity were anorexia (4%), diarrhea (2%), and rash (2%), and those due to hematological toxicity were neutropenia (36%), anemia (12%), and thrombocytopenia (2%). CONCLUSION: Although the triweekly six-course regimen of TCbH achieved a high pCR rate, hematological AEs frequently occurred during the latter part of the chemotherapy course. One-third of patients experienced delayed or discontinued chemotherapy. Clinical registration number: http://www.umin.org.au UMIN000013513.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Anorexia/induzido quimicamente , Povo Asiático , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carboplatina/administração & dosagem , Docetaxel , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Neutropenia/induzido quimicamente , Receptor ErbB-2/metabolismo , Taxoides/administração & dosagem , Trastuzumab/administração & dosagemRESUMO
BACKGROUND: Eribulin mesylate (eribulin) is a first-in-class halichondrin B-based microtubule dynamics inhibitor. To compare the anti-angiogenic activity of eribulin to that of bevacizumab, we compared tumour vessel remodelling and reoxygenation between the two agents. METHODS: Patients with advanced breast cancer with stage III/IV were eligible for the study. Patients were assigned to receive either eribulin or single-agent bevacizumab. Tissue concentrations of oxyhaemoglobin (O2Hb) and deoxyhaemoglobin (HHb), and oxygen saturation (SO2) of breast tumours before and day 7 after the first infusion were repeatedly measured using diffuse optical spectroscopic imaging (DOSI). A pair of blood samples was collected for multiplex biomarker studies. RESULTS: Baseline DOSI measurement of all 29 patients (eribulin, n=14 and bevacizumab, n=15) revealed significantly higher tumour concentrations of O2Hb and HHb than that in the normal breast tissue. After eribulin treatment, DOSI revealed a significant decrease in HHb concentration and increased SO2 during the observation period. This trend was not observed for bevacizumab. Instead, bevacizumab significantly decreased the concentration of O2Hb. The multiplex biomarker study revealed that both eribulin and bevacizumab decreased plasma concentrations of VEGF and bFGF, but only eribulin treatment suppressed the plasma concentration of TGF-ß1. CONCLUSIONS: Eribulin, but not bevacizumab, treatment increased tumour SO2. Suppression of TGF-ß1 by eribulin could have a favourable anti-angiogenic effect. Our results suggest that differences in vascular remodelling between these two agents may account for their different effects on tumour reoxygenation.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Furanos/uso terapêutico , Cetonas/uso terapêutico , Oxigênio/metabolismo , Moduladores de Tubulina/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Hemodinâmica/efeitos dos fármacos , Hemoglobinas/análise , Humanos , Proteínas de Neoplasias/sangue , Oxiemoglobinas/análise , Paclitaxel/administração & dosagem , Espectroscopia de Luz Próxima ao Infravermelho , Fator de Crescimento Transformador beta1/sangue , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT3) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT3 receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT3 receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.
Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Oncologia , Náusea/induzido quimicamente , Guias de Prática Clínica como Assunto , Vômito/induzido quimicamente , Dexametasona/uso terapêutico , Humanos , Japão , Náusea/tratamento farmacológico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Sociedades Médicas , Fatores de Tempo , Vômito/tratamento farmacológicoRESUMO
BACKGROUND: Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy. METHODS: The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80-120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently. RESULTS: Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8-79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed. CONCLUSIONS: The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469.
Assuntos
Antraciclinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Ácido Oxônico/administração & dosagem , Tegafur/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/patologia , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Ácido Oxônico/efeitos adversos , Tegafur/efeitos adversosRESUMO
OBJECTIVE: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free paclitaxel coupled to human albumin without an associated increase in toxicity. The neoadjuvant study of primary breast cancer was planned to evaluate tumor response and safety of triweekly nanoparticle albumin-bound paclitaxel. METHODS: Patients with Stage II/III HER2-negative primary breast cancer received four courses of nanoparticle albumin-bound paclitaxel 260 mg/m(2) every 3 weeks (q3w), followed by four courses of epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) q3w. Tumor response after nanoparticle albumin-bound paclitaxel was histologically evaluated. In addition, the clinical response, breast-conserving rate and safety of this treatment were monitored. RESULTS: Among 53 patients who received nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide neoadjuvant chemotherapy, pathological complete response and near-pathological complete response were confirmed in 3 (5.7%) and 7 (13.2%) patients who had surgery, respectively. The overall objective response rate was 71.7% after completion of chemotherapy. Based on Positron Emission Tomography Response Criteria in Solid Tumors using (18)F-fluorodeoxyglucose, complete metabolic response and partial metabolic response after 2-3 courses of nanoparticle albumin-bound paclitaxel were 15.1 and 52.8%, respectively. The most common significant toxicities of q3w nanoparticle albumin-bound paclitaxel were Grade 3 muscle pain, neuropathy and febrile neutropenia, each in 1 (1.9%) patient. There were no incidences of anaphylaxis or Grade 4/5 adverse events. CONCLUSION: Neoadjuvant chemotherapy using q3w nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide was feasible in breast cancer patients with acceptable clinical response and drug tolerance, but conferred a low rate of pathological complete response. Monotherapy with q3w nanoparticle albumin-bound paclitaxel could be an appropriate substitute for solvent-based taxane in terms of therapeutic and safety management.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Adulto , Idoso , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Biomarcadores Tumorais/análise , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Docetaxel , Esquema de Medicação , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fluordesoxiglucose F18 , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Nanopartículas , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
Near-infrared diffuse optical spectroscopy (DOS) imaging can non-invasively measure tumor hemoglobin concentration using high contrast to normal tissue, thus providing vascularity and oxygenation status. We assessed the clinical usefulness of DOS imaging in primary breast cancer. In all, 118 women with a histologically confirmed diagnosis of primary malignant tumor were enrolled. All participants underwent testing using time-resolved DOS before treatment initiation. Visual assessment of DOS imaging for detecting tumors was carried out by two readers blinded to the clinical data. Relative total hemoglobin (rtHb) and oxygen saturation (stO2 ) of the tumors was compared with clinicopathological variables and 10-year prognosis was calculated. Sensitivity for detecting a tumor based on the rtHb breast map was 62.7% (74/118). The sensitivity depended on T stage: 100% (7/7) for T3, 78.9% (45/57) for T2, 44.7% (17/38) for T1, and 31.3% (5/16) for Tis . Tumors showed unique features of higher rtHb with a wider range of stO2 than normal breast tissue, depending on histological type. There was a significant correlation of rtHb with tumor size, lymphatic vascular invasion, and histological grade, and of stO2 with age and tumor size. Neither rtHb nor stO2 correlated with intrinsic biomarkers such as estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2; rtHb inversely correlated with 10-year relapse-free survival and overall survival, with statistical significance. Diffuse optical spectroscopy imaging has limited utility for the early detection of breast cancer; nonetheless, the findings suggest that the degree of tumor angiogenesis and hypoxia may be associated with tumor aggressiveness and poor prognosis.
Assuntos
Neoplasias da Mama/diagnóstico , Diagnóstico por Imagem/métodos , Neovascularização Patológica/diagnóstico , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/patologia , Detecção Precoce de Câncer/métodos , Feminino , Hemoglobinas/análise , Humanos , Hipóxia/diagnóstico , Glândulas Mamárias Humanas/irrigação sanguínea , Glândulas Mamárias Humanas/patologia , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Because of its superior efficacy to tamoxifen, anastrozole has been widely used in Japan as an adjuvant treatment for postmenopausal, hormone-responsive breast cancer patients. However, anastrozole may affect bone in Japanese patients similar to its effects in Western patients. The aim of this study is to evaluate the rate of bone fracture and bone mineral density (BMD) during anastrozole treatment in Japanese patients. PATIENTS AND METHODS: In this study, 350 postmenopausal women with hormone-responsive, stage I to IIIA breast cancer were enrolled and scheduled to receive adjuvant anastrozole treatment for up to 5 years. Patients underwent clinical examination for bone fractures and annual measurement of BMD during treatment. RESULTS: After a median follow-up of 33.0 months, bone fractures occurred in 1.8 %. Annual fracture rates were 0.3 and 1.2 % during the first and second year, respectively. The overall median BMD significantly decreased, measuring 87.5, 84.3, and 83.5 % at baseline and after 1 and 2 years, respectively. Musculoskeletal disorders were the most common (26.1 %), and hot flashes were the second most common adverse event (7.9 %). Severe adverse events occurred in 5.5 % of all the cases. CONCLUSIONS: In this interim analysis, the bone fracture rate was lower than that in the Western population despite a significant reduction of BMD after 2 years of treatment with anastrozole. Adjuvant anastrozole treatment was well tolerated in Japanese postmenopausal women with breast cancer. Long-term follow-up data is necessary to elucidate the racial disparities of the safety profile of anastrozole.
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Neoplasias da Mama/tratamento farmacológico , Fraturas Ósseas/induzido quimicamente , Nitrilas/administração & dosagem , Triazóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Densidade Óssea , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Feminino , Fraturas Ósseas/patologia , Humanos , Japão , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Pós-Menopausa , Resultado do Tratamento , Triazóis/efeitos adversosRESUMO
We report a case of a trastuzumab-resistant human epidermal growth factor receptor-2(HER2)-positive breast cancer patient with extensive liver metastases and associated impaired liver function, who showed an excellent response to the combination of trastuzumab and capecitabine. The patient was a 59-year-old postmenopausal woman with multiple liver metastases at first examination. She first received anthracycline-based chemotherapy, and after progression was followed up with a combination of trastuzumab and paclitaxel. Despite an initial response to this treatment, liver metastases rapidly progressed. Although palliative treatment was considered because of her impaired liver function, she received capecitabine while continuing trastuzumab. This combination therapy showed an excellent response, and a good quality of life(QOL)was maintained for a long time without any severe adverse events. The continuation of trastuzumab is considered effective after having progressed by trastuzumab including pretreatment, and we consider it worth while to give a combination of trastuzumab and capecitabine to patients with extensive liver metastases and associated impaired liver function, because of the treatment's synergistic effect and low risk of causing severe adverse events.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Receptor ErbB-2/análise , TrastuzumabRESUMO
BACKGROUND: To assess the usefulness of positron emission tomography combined with computed tomography using (18)F-fluorodeoxyglucose (FDG PET/CT) for optimizing chemotherapy during neoadjuvant chemotherapy for primary breast cancer. METHODS: One hundred and eight patients (110 tumors) with breast cancer (≥2 cm, stages II and III) received neoadjuvant chemotherapy consisting of an anthracycline-based regimen and taxane. The maximal value of the baseline standardized uptake value (SUV) and the change in SUV after four cycles of an anthracycline-based regimen relative to baseline SUV were assessed for predicting pathological complete response (pCR) after sequential taxane. RESULTS: Tumors with pCR had significantly higher baseline SUV (9.3 ± 3.7 SD) compared to those with non-pCR (7.2 ± 3.8 SD) (p = 0.02), but there was a considerable overlap between two groups. On PET scan after four cycles of chemotherapy, thirty-three patients (33.7%) with a 72.1% or greater reduction in SUV were considered as responders and the performance in predicting pCR had a sensitivity of 88.9% and specificity of 78.7%. CONCLUSION: The baseline SUV could not be a useful indicator for predicting pCR due to the wide range in sensitivity. On the other hand, a relative change in SUV after completion of an anthracycline-based regimen could be useful for predicting pCR.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Taxoides/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND/AIM: There are few models predicting breast cancer prognosis among patients receiving neoadjuvant chemotherapy (NAC) for estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (luminal) breast cancer. We examined whether biological features (BFs) of residual tumors are prognostic factors following NAC. PATIENTS AND METHODS: We enrolled patients with remnant tumors following NAC for luminal breast cancer and evaluated clinical stage, pathological stage, BFs prior to NAC, and BFs following NAC as prognostic factors. BFs were divided into high and low risk using the previously reported YR-IHC4 model calculated according to ER, progesterone receptor (PgR), HER2, and the proliferation marker Ki-67. RESULTS: A total of 57 patients were enrolled in the current study. We observed a statistically significant difference in relapse-free survival (RFS) between the BF risk categories via YR-IHC4 predictions following NAC (p=0.044). The 5-year RFS rates of the BF low- and high-risk groups following NAC were 84.2% and 52.5%, respectively. CONCLUSION: BFs of residual tumors following NAC may be important prognostic factors in luminal breast cancer.
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Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
Background: Matrix-producing carcinoma (MPC) is a rare tumor accounting for 0.1% of all breast cancers. Although MPC is usually triple-negative breast cancer, there have been few reports of preoperative chemotherapy for MPC that is considered chemotherapy-resistant. Herein, we report a case of MPC that was successfully treated with preoperative chemotherapy. Case Description: The patient was a 47-year-old woman diagnosed with right multiple breast cancer, clinical stage IIA. One of the tumors was identified as MPC and the other was invasive ductal carcinoma. The maximum tumor diameter of MPC was 3.8-cm. On immunohistochemistry, the tumor cells of MPC tested negative for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). The Ki67 index was 90%. Preoperative chemotherapy was performed. EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) was administered every 3 weeks for a total of 4 courses, followed by 12 courses of weekly paclitaxel (80 mg/m2). Then, she underwent right skin-sparing mastectomy, sentinel lymph node biopsy, and deep inferior epigastric perforator flap reconstruction. There was no metastasis to the sentinel lymph nodes. Postoperative pathological results showed that the residual tumor of the MPC measured only 0.1 cm. On the other hand, the residual tumor of the invasive ductal carcinoma was 0.7 cm. Endocrine therapy with oral tamoxifen was initiated for the invasive ductal carcinoma. Three years after surgery, no recurrence was observed. It has been reported that prognosis was correlated with residual cancer after preoperative chemotherapy. In addition, preoperative chemotherapy is of high clinical significance for the selection of postoperative treatment. Conclusions: Although our case of MPC was successfully treated with preoperative chemotherapy, the standard of care for MPC remains uncertain. Development of a new targeted therapy for MPC is warranted.
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alpha-Synuclein is one of the causative proteins of the neurodegenerative disorder, Parkinson's disease. Deposits of alpha-synuclein called Lewy bodies are a hallmark of this disorder, which is implicated in its progression. In order to understand the mechanism of amyloid fibril formation of alpha-synuclein in more detail, in this study we have isolated a specific, ~20 residue peptide region of the alpha-synuclein fibril core, using a combination of Edman degradation and mass-spectroscopy analyses of protease-resistant samples. Starting from this core peptide sequence, we then synthesized a series of peptides that undergo aggregation and fibril formation under similar conditions. Interestingly, in a derivative peptide where a crucial phenylalanine residue was changed to a glycine, the ability to initiate spontaneous fibril formation was abolished, while the ability to extend from preexisting fibril seeds was conserved. This fibril extension occurred irrespective of the source of the initial fibril seed, as demonstrated in experiments using fibril seeds of insulin, lysozyme, and GroES. This interesting ability suggests that this peptide might form the basis for a possible diagnostic tool useful in detecting the presence of various fibrillogenic factors.
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Amiloide/química , Amiloide/metabolismo , Corpos de Lewy/química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/isolamento & purificação , alfa-Sinucleína/química , Sequência de Aminoácidos , Benzotiazóis , Dicroísmo Circular , Humanos , Insulina/química , Insulina/metabolismo , Microscopia de Força Atômica , Dados de Sequência Molecular , Fragmentos de Peptídeos/metabolismo , Tiazóis/metabolismo , alfa-Sinucleína/metabolismoRESUMO
Regional lymph node status is the most important prognostic factor in breast cancer. Sentinel lymph node biopsy is the standard method of axillary staging in early breast cancer patients with clinically negative nodes. Preoperative lymphoscintigraphy might support refining biopsy findings by determining the number and location of sentinel lymph nodes. In aged or overweight patients, in the presence of atypical or extra-axillary lymphatic drainage, non-visualized lymph nodes, or sentinel lymph nodes close to the isotope injection site, detection could be aided by a new, hybrid imaging tool: the single-photon emission computed tomography combined with computed tomography (3D SPECT/CT). For the first time in Hungarian language, authors overview the literature: all 14 English-language articles on the implementation of 3D SPECT/CT in sentinel lymph node detection in breast cancer are included. It is concluded that 3D SPECT/CT increases the success rate and quality of preoperative sentinel node identification, and is capable of providing a more accurate staging of breast cancer patients in routine clinical practice.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Biópsia de Linfonodo Sentinela/métodos , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Axila , Neoplasias da Mama/patologia , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Estadiamento de Neoplasias , Compostos de Organotecnécio , Ácido Fítico , Compostos Radiofarmacêuticos , Rênio , Compostos de Tecnécio , Agregado de Albumina Marcado com Tecnécio Tc 99m , Coloide de Enxofre Marcado com Tecnécio Tc 99mRESUMO
BACKGROUND/AIM: Oncotype DX recurrence score (RS) for breast cancer is a useful tool for determining chemotherapy indication but it is expensive and time-consuming. We determined whether four immuno-histochemical markers, namely human epidermal growth factor 2 (HER2), estrogen receptor (ER), progesterone receptor (PgR), and Ki-67, are predictive of an RS ≥26 in Japanese patients. PATIENTS AND METHODS: The study included 95 Japanese patients evaluated for RS. A predictive model was created using logistic regression analysis. RESULTS: The discriminant function was calculated as follows: p=1/{1+exp [-(4.611+1.2342×HER2-0.0813×ER- 0.0489 ×PgR+0.0857×Ki67)]}. Using a probability of 0.5 as the cutoff, the accuracy, sensitivity, specificity, positive predictive and negative predictive values were 90.5%, 72.2%, 94.8%, 76.4% and 93.5%, respectively. CONCLUSION: The model had a high negative predictive value in predicting RS ≥26 in Japanese patients, indicating that Oncotype DX testing may be omitted in patients with a negative result according to the predictive model.
Assuntos
Neoplasias da Mama , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Fator de Crescimento Epidérmico , Feminino , Perfilação da Expressão Gênica , Humanos , Recidiva Local de Neoplasia/genética , Prognóstico , Receptor ErbB-2/genética , Receptores de Estrogênio/genéticaRESUMO
PURPOSE: A novel approach was introduced for breast surgery using the BiClamp, a new bipolar thermal energy device, to avoid complications and to shorten the time required for the dissection of the axillary lymph nodes. METHODS: Thirty-six patients with early breast cancer were assessed. The surgical parameters were compared between the procedures performed using the BiClamp technique (n = 14) and conventional surgery with suture ligation (n = 22). The parameters included the operation time, blood loss, and discharge on the first postoperative day. In addition, each of those parameters was compared between the patients with a high body mass index (BMI) (>22) and a low BMI (< or =22). The sealed vessels were examined histologically and heat-associated morphological vessel wall alterations were evaluated. RESULTS: The operation time was significantly shorter in the BiClamp group than in the control group (P = 0.017, 90 +/- 18 vs 115 +/- 33 min). In addition, the blood loss in the BiClamp group tended to be smaller than in the control group, but the difference was not significant (P = 0.54, 61 +/- 47 vs 74 +/- 67 g). No other parameters showed any significant differences between the two groups. CONCLUSION: The BiClamp thermofusion technique was safe and useful in breast surgery involving axillary dissection.
Assuntos
Neoplasias da Mama/cirurgia , Mama/cirurgia , Temperatura Alta/uso terapêutico , Excisão de Linfonodo/instrumentação , Linfonodos/cirurgia , Axila/cirurgia , Feminino , Humanos , Ligadura/instrumentação , Ligadura/métodos , Excisão de Linfonodo/métodos , Pessoa de Meia-Idade , Instrumentos Cirúrgicos , Técnicas de Sutura/instrumentação , Fatores de Tempo , Resultado do TratamentoRESUMO
Recent developments in chemotherapeutic regimens have improved overall and progression-free survival in patients with various malignancies. Supportive care accompanied by antiemetic treatment is crucial for successful chemotherapy. Hence, high-level evidence with regard to antiemetic therapy is essential to create awareness among oncologists. This study reviewed evidence from clinical trials involving antiemetic therapy in Japanese patients with malignancies, and established an antiemetic guideline for oncologists in Japan. Here, we introduce the outline of this antiemetic guideline.
Assuntos
Antieméticos/normas , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Guias como Assunto , Humanos , Japão , Náusea/induzido quimicamente , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controleRESUMO
A series of novel and potent 3-amidinophenylsulfonamide derivatives of factor Xa inhibitors were designed and synthesized using an amidoxime prodrug strategy. We focused on systemic clearance of parent compounds in rats, and performed in vivo pharmacokinetic screening. Incorporation of a carboxymethoxy group markedly improved systemic clearance (compound 43), and the related amidoxime 44 showed sufficient prodrug conversion. Compound 45, the double prodrug of 43, exhibited practicable bioavailability after oral administration in rats. Among the various compounds under investigation, KFA-1982 was selected for clinical development.