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1.
Chemotherapy ; 62(5): 307-313, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28605730

RESUMO

BACKGROUND: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. METHODS: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety. RESULTS: A total of 42 patients were enrolled in this study. The objective response rate and clinical benefit rate were 24 and 43%, respectively. The median progression-free survival was 4.0 months. The median overall survival was 11.1 months. Grade 3/4 neutropenia was the most common hematologic toxicity, occurring in 22 patients (54%). Nonhematologic toxicity was moderate and transient, with fatigue (48%) being the most common condition and no severe adverse event reported. CONCLUSION: The combination of gemcitabine and vinorelbine is an effective and tolerable regimen for HER2-negative, taxane-pretreated, metastatic breast cancer patients in Japan.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Vimblastina/análogos & derivados , Adulto , Idoso , Neoplasias da Mama/patologia , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/etiologia , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Taxoides , Resultado do Tratamento , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Vinorelbina , Gencitabina
2.
Gan To Kagaku Ryoho ; 43(3): 349-51, 2016 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-27067853

RESUMO

We report a case of breast cancer with multiple liver metastases successfully treated with capecitabine monotherapy after failure of combination therapy comprising bevacizumab (Bev) and paclitaxel (PTX). In March 2012, a 67-year-old woman was diagnosed with Stage IV breast cancer with massive pleural effusion. Histological examination showed invasive ductal carcinoma (scirrhous carcinoma) that was positive for hormonal receptor but negative for HER2 expression, and the nuclear grade was 1. She first received chemotherapy to decrease the tumor volume followed by hormonal therapy. After progression, imaging studies showed increased multiple lung and liver metastases and pleural effusion. Subsequently, treatment with combination of Bev and PTX was started from July 2014. After 4 courses of the combination therapy, multiple liver metastases were unchanged, but her liver function was impaired. Hence, she received capecitabine monotherapy (1,800 mg bis in die [BID]; 2-week administration followed by a week of rest). Her liver function improved early, and a partial response (PR) in the multiple liver metastases was achieved 3 months after initiation of therapy. Furthermore, the metastatic lesions were well controlled 4 months later. These findings suggest that the sensitivity to an anticancer agent greatly varies among patients.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Capecitabina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Humanos , Neoplasias Hepáticas/secundário , Paclitaxel/administração & dosagem , Terapia de Salvação
3.
Anticancer Res ; 43(6): 2783-2789, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37247903

RESUMO

BACKGROUND/AIM: Palbociclib was the first cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved worldwide. Currently, CDK4/6 inhibitors are strongly recommended for endocrine therapy in the first or second line with hormone receptor-positive advanced breast cancer. It is expected the use of CDK4/6 inhibitor will further increase. Therefore, the aim was to investigate and better understand the use of palbociclib. PATIENTS AND METHODS: We retrospectively analyzed the data of patients with advanced breast cancer who were treated with palbociclib in three hospitals between 2018 and 2022. Clinical data were obtained from the patients' medical electronic records. RESULTS: A total of 143 patients were enrolled. The median age was 66 years (range=33-89), and the majority (90.9%) were postmenopausal patients. In total, median time-to-treatment discontinuation (TTD) (95% confidence interval, CI) was 7 (6-10) months. Median TTD (95% CI) was 13 (7-20) months for the first or second line, and significantly prolonged compared to TTD for the third or later lines with palbociclib (p<0.0001). The importance of front-line use was indicated. Multivariate analyses showed that no visceral metastasis or first or second line therapy influenced the longer TTD. Between patients above or below 70 years of age, older age did not negatively affect TTD, though there were significantly more cases of dose reduction or withdrawal in patients over 70 years old. The variation of adverse events (AEs) among hospitals was very large (9.0%, 31.3%, 4.5%). We found that understanding of AE management was important. CONCLUSION: This study showed that dose reduction or withdrawal of palbociclib had no harmful effects in Japanese patients. Efficacy was also high in older patients. It is important to manage palbociclib administration more safely and appropriately. A combination of dose reduction and withdrawal is key to this therapeutic strategy.


Assuntos
Neoplasias da Mama , Idoso , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Receptor ErbB-2 , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais
4.
Jpn J Clin Oncol ; 41(7): 918-23, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21693482

RESUMO

Fibroadenoma is the most common form of benign breast tumor and the most common breast tumor in women under 30 years of age. However, carcinoma arising within a fibroadenoma is unusual, with over 100 cases reported in the literature. Histological diagnosis is typically unexpected. A 46-year-old female with no family history of breast malignancies was admitted for an elastic hard lump in the upper-outer quadrant of her right breast. At a clinic that she visited previously, her condition was diagnosed by core needle biopsy with four specimens showing fibroadenoma with borderline atypical ductal hyperplasia at pathology. Excisional biopsy was recommended for pathological diagnosis. The patient requested a definitive diagnosis and alternative treatment to tumorectomy. More biopsy specimens were needed for pathological diagnosis; therefore, ultrasonography-guided vacuum-assisted core needle biopsies were obtained, confirming ductal carcinoma in situ with questionable microinvasion of intracanalicular- and pericanalicular-type fibroadenoma. Right breast-conserving surgery and sentinel lymph node biopsy were immediately performed for radical therapy. We present this case to increase awareness of this entity and stress the need for histological evaluation of some breast masses.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/cirurgia , Fibroadenoma/diagnóstico , Fibroadenoma/cirurgia , Biópsia por Agulha/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Progressão da Doença , Feminino , Fibroadenoma/diagnóstico por imagem , Fibroadenoma/patologia , Humanos , Imuno-Histoquímica , Mastectomia Segmentar , Pessoa de Meia-Idade , Biópsia de Linfonodo Sentinela , Ultrassonografia Mamária
5.
Breast Dis ; 34(1): 9-17, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23507670

RESUMO

BACKGROUND: For locally advanced breast cancer, neoadjuvant chemotherapy (NAC) is the standard of care for downstaging the tumor prior to surgery, and improved prognoses that are associated with pathological complete responses (pCR) have been noted, particularly in patients with human epidermal growth factor receptor 2 (HER2)-positive and triple negative (TN) tumors. OBJECTIVE: The aim of this study was to assess the differences in pathological responses among intrinsic subtypes of local lesions and status of axillary lymph nodes (Ax LN). METHODS: A consecutive series of 134 patients with locally advanced breast cancer who were treated with NAC was analyzed. Tumors were classified into the following 5 subtypes according to immunohistochemical staining results: Luminal A type, Luminal B type (HER2-negative and HER2-positive), HER2 type, and TN type. RESULTS: In Luminal A, Luminal B (HER2-negative), Luminal B (HER2-positive), HER2, and TN tumors, the pCR rates were 10% (4 of 40), 19% (8 of 42), 42% (8 of 19), 59% (10 of 17), and 38% (6 of 16), respectively. HER2-positive tumors showed good therapeutic effects, while Luminal A tumors showed less therapeutic effects. CONCLUSIONS: Strategies that are determined according to intrinsic subtypes are becoming very important in the treatment of locally advanced breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Metástase Linfática , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Receptor ErbB-2/análise
6.
Breast Cancer Res Treat ; 101(3): 305-15, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16821082

RESUMO

BACKGROUND: Present study was aimed to investigate the relationship of p53 mutation status with response to docetaxel in breast cancers. In addition, attempts were made to identify the genes differentially expressed between p53-wild and p53-mutated breast tumors and to study their relationship with response to docetaxel. METHODS: Mutational analysis of p53 was done in 50 breast tumor samples obtained from primary breast cancer patients (n = 33) and locally recurrent breast cancer patients (n = 17) before docetaxel therapy. Response to docetaxel was evaluated clinically. Gene expression profiling (n = 2,412) was conducted by adapter-tagged competitive-PCR in 186 tumor samples, which were also analyzed in their p53 mutational status in order to identify the differentially expressed genes according to p53 mutation status and their relationship with response to docetaxel. RESULTS: Response rate of p53-mutated tumors (44%) was lower than that of p53-wild tumors (62%) though there was no statistical significance (P = 0.23). Of 2412 genes, mRNA expression of 13 genes was significantly different between p53-wild and p53-mutated tumors. Of these 13 genes, mRNA expression of CCT5, RGS3, and YKT6 was significantly up-regulated in p53-mutated tumors and associated with a low response rate to docetaxel. Treatment of MCF-7 cells with siRNA specific for CCT5, RGS3, or YKT6 resulted in a significant enhancement of docetaxel-induced apoptosis. CONCLUSIONS: CCT5, RGS3, and YKT6 mRNA expressions, which are up-regulated in p53-mutated breast tumors, might be implicated in resistance to docetaxel and clinically useful in identifying the subset of breast cancer patients who may or may not benefit from docetaxel treatment.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Genes p53/genética , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Taxoides/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Linhagem Celular , Chaperonina com TCP-1 , Chaperoninas , Quimioterapia Adjuvante , Análise Mutacional de DNA , DNA de Neoplasias/genética , Docetaxel , Feminino , Proteínas de Ligação ao GTP/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica/efeitos dos fármacos , Humanos , Chaperonas Moleculares/metabolismo , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Proteínas R-SNARE/metabolismo , Proteínas RGS , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , Resultado do Tratamento , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética
7.
Cell ; 109(1): 113-24, 2002 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-11955451

RESUMO

Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric cancer cells do not significantly express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of human gastric cancer cell lines in nude mice was inversely related to their level of RUNX3 expression, and a mutation (R122C) occurring within the conserved Runt domain abolished the tumor-suppressive effect of RUNX3, suggesting that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer.


Assuntos
Divisão Celular/genética , Transformação Celular Neoplásica/genética , Proteínas de Ligação a DNA/deficiência , Epitélio/metabolismo , Mucosa Gástrica/metabolismo , Neoplasias Gástricas/genética , Fatores de Transcrição/deficiência , Proteínas Supressoras de Tumor/deficiência , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Divisão Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Subunidade alfa 3 de Fator de Ligação ao Core , Metilação de DNA , Proteínas de Ligação a DNA/genética , Epitélio/patologia , Epitélio/fisiopatologia , Éxons/genética , Feminino , Deleção de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Marcação de Genes , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Hiperplasia/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Estrutura Terciária de Proteína/genética , Estômago/patologia , Estômago/fisiopatologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/fisiopatologia , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética
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