RESUMO
The 4-5% of the breast cancer patients have metastases in the eye. We present the case of a 30-year-old woman with an infiltrant duct carcinoma of the breast pT2N2M0 HER2 positive. Six months after primary radical treatment she had a systemic relapse with multiples metastatic sites, so several treatment with trastuzumab in combination with chemotherapy were started. After 4 years patient presented multiple white-coloured micronodules in the iris of the right eye. Only a 3-7.8% of ocular metastases are located in the iris. With mantenaince therapy with trastuzumab natural history of the illness has changed. Several studies had analyzed if metastases in the brain during treatment with trastuzumab have increased in comparison with the pretrastuzumab era. The infrequent presentation of metastases in the anterior uveal makes difficult to establish if it is an spontaneous fact or if it is favoured by trastuzumab treatment.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Neoplasias da Íris/secundário , Adulto , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Feminino , Humanos , Neoplasias da Íris/terapiaRESUMO
Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quinases Ciclina-Dependentes/antagonistas & inibidores , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Animais , Ciclo Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Humanos , Piperazinas/farmacologia , Piridinas/farmacologiaRESUMO
Breast cancer is a burden for western societies, and an increasing one in emerging economies, because of its high incidence and enormous psychological, social, sanitary and economic costs. However, breast cancer is a preventable disease in a significant proportion. Recent developments in the armamentarium of effective drugs for breast cancer prevention (namely exemestane and anastrozole), the new recommendation from the National Institute for Health and Care Excellence to use preventative drugs in women at high risk as well as updated Guidelines from the US Preventive Services Task Force and the American Society of Clinical Oncology should give renewed momentum to the pharmacological prevention of breast cancer. In this article we review recent major developments in the field and examine their ongoing repercussion for breast cancer prevention. As a practical example, the potential impact of preventive measures in Spain is evaluated and a course of practical actions is delineated.
Assuntos
Neoplasias da Mama/prevenção & controle , Antineoplásicos Hormonais/uso terapêutico , Proteína BRCA1/genética , Neoplasias da Mama/genética , Feminino , Humanos , Tamoxifeno/uso terapêuticoRESUMO
An immunoradiometric assay was used to determine the presence of p29 protein in 68 breast cancer cyTOSOLS. The p29 values ranged from 0 to 1123 U/mg, with a mean value of 127 +/- 28.7 U/mg. Using a cutoff point of 20 U/mg the frequency of p29 positive tumors was about 55%. A quantitative and qualitative relation was found between p29 and estrogen receptor (ER), but not between p29 and progesterone receptor (PR). Discordance between p29 and ER status was found in 13 out of 68 tumors. Both the frequency of p29 positive tumors and the p29 values were significantly higher in postmenopausal than in premenopausal women, in a similar way to ER but different from PR. There was no difference in p29 content between primary tumor and metastasis. We did not find any relation among p29 primary tumors content and axillary lymph nodes involvement or tumor size.
Assuntos
Neoplasias da Mama/análise , Fosfoproteínas/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Menopausa , Pessoa de Meia-IdadeRESUMO
Between January 1982 and February 1985, 70 breast cancer patients with histologically confirmed axillary node involvement and T1-3a were treated following surgery with a combination of adriamycin, fluorouracil, cyclophosphamide, methotrexate, with or without tamoxifen according to the estrogen and progesterone receptors state. At 60 months of study (median follow-up, 41 months), the estimated proportion remaining disease-free was 62%. The estimated survival rate was 81%. A comparison of the actuarial disease-free and overall survival with data reported in the literature indicates a similar positive effect of adjuvant systemic therapy as described in adjuvant studies using polychemotherapy regimens. Patient acception of chemotherapy regimen was generally good. This can be accounted for because of an adequate emesis control and real compliance of the patients with the oncologist.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/cirurgia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Tamoxifeno/administração & dosagemRESUMO
HER2-positive breast cancer, accounting for 15 % of the total breast cancer patient population, carries in itself a bad prognosis, which has now become much better after the advent of anti-HER2 drugs. HER2-targeted therapy has significantly improved disease free- and overall survival in HER2-positive breast cancer, and has rendered better disease control both in the early and advanced disease setting. Trastuzumab treatment duration is often prolonged and poses significant time and resource challenges both on the treatment institutions and on the patient. The recent development of a subcutaneous formulation has meant a significant advance in this respect. We review the drug development of the compound and the current evidence on its use.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Descoberta de Drogas , Feminino , Humanos , Injeções Subcutâneas , Receptor ErbB-2/metabolismo , TrastuzumabRESUMO
Breast cancer is a burden for western societies, and an increasing one in emerging economies, because of its high incidence and enormous psychological, social, sanitary and economic costs. However, breast cancer is a preventable disease in a significant proportion. Recent developments in the armamentarium of effective drugs for breast cancer prevention (namely exemestane and anastrozole), the new recommendation from the National Institute for Health and Care Excellence to use preventative drugs in women at high risk as well as updated Guidelines from the US Preventive Services Task Force and the American Society of Clinical Oncology should give renewed momentum to the pharmacological prevention of breast cancer. In this article we review recent major developments in the field and examine their ongoing repercussion for breast cancer prevention. As a practical example, the potential impact of preventive measures in Spain is evaluated and a course of practical actions is delineated (AU)
No disponible
Assuntos
Humanos , Feminino , Neoplasias da Mama/prevenção & controle , Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Marcadores Genéticos , Predisposição Genética para Doença , Fatores de Risco , Genes Neoplásicos , Genes BRCA1 , Genes BRCA2Assuntos
Neoplasias da Mama/imunologia , Enzimas Ativadoras do Complemento/análise , Proteínas Inativadoras do Complemento 1/análise , Complemento C1/análise , Complemento C3/análise , Complemento C4/análise , Proteínas do Sistema Complemento/análise , Adulto , Idoso , Neoplasias da Mama/terapia , Complemento C1q , Feminino , Humanos , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib
No disponible
Assuntos
Humanos , Animais , Inibidor p16 de Quinase Dependente de Ciclina/farmacocinética , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Inibidores da Aromatase/uso terapêutico , Ensaios Clínicos como Assunto , Biomarcadores Tumorais/análise , Piperazinas/uso terapêuticoRESUMO
Epidermal growth factor receptor (EGFr) and cytosolic (cER) and nuclear (nER) estradiol receptors were quantified in 220 primary breast cancers. The EGFr was significantly more frequent (X2 = 5.9; P less than 0.025) and its concentration was significantly higher (P less than 0.001) among ER- tumors than in ER+ tumors. There was a significantly greater proportion (X2 = 6.4; P less than 0.05) of node involvement in EGFr+/ER+ tumors than in EFGr/ER+. Increases in the proportion of EGFr+ in ER- tumors are parallel to Scarff-Bloom scores (X2 = 6.1; P less than 0.05) and there is a significant trend towards increased EGFr concentrations with histologic dedifferentiation. In ER+ tumors the median concentrations of EGFr in the different age groups show linear correlation and follow a parallel profile with the medians of nER. These findings support the hypothesis that considers EGFr as a bad prognosis factor and suggest that EGFr expression and concentration in ER+ tumors might be considered an estrogenic action mediated through the binding of ER to their nuclear acceptors.
Assuntos
Neoplasias da Mama/análise , Fator de Crescimento Epidérmico/fisiologia , Receptores ErbB/análise , Fatores Etários , Neoplasias da Mama/patologia , Núcleo Celular/análise , Citosol/análise , Humanos , Metástase Neoplásica , Prognóstico , Receptores de Estradiol/análiseRESUMO
HER2-positive breast cancer, accounting for 15 % of the total breast cancer patient population, carries in itself a bad prognosis, which has now become much better after the advent of anti-HER2 drugs. HER2-targeted therapy has significantly improved disease free- and overall survival in HER2-positive breast cancer, and has rendered better disease control both in the early and advanced disease setting. Trastuzumab treatment duration is often prolonged and poses significant time and resource challenges both on the treatment institutions and on the patient. The recent development of a subcutaneous formulation has meant a significant advance in this respect. We review the drug development of the compound and the current evidence on its use (AU)
No disponible
Assuntos
Humanos , Feminino , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante , Antineoplásicos/uso terapêutico , Prognóstico , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos/metabolismo , Administração Intravenosa/métodos , Administração Intravenosa , Resultado do Tratamento , Avaliação de Eficácia-Efetividade de IntervençõesRESUMO
Neutropenia is a common complication of cancer chemotherapy. Colony-stimulating factors (CSF) may be used to avoid neutropenia-associated complications. The Spanish Society of Medical Oncology (SEOM) recently constituted a working group to review the main issues concerning the use of CSF and carried out a consensus process about the use of CSF in cancer patients, held in Madrid on 26 May 2006. The group concluded the following recommendations: prophylactic use of CSF is recommended when a rate of febrile neutropenia (FN) higher than 20% is expected without the use of CSF or when additional risk factors for neutropenia exist; therapeutic use of CSF is recommended in order to treat FN episodes but not to treat afebrile neutropenic episodes. In addition, the use of CSF is considered effective when used to mobilise stem cells before high-dose chemotherapy and when used for chemotherapy schedule optimisation in dose-dense and in dose-intense regimens (AU)
Assuntos
Humanos , Masculino , Feminino , Fatores Estimuladores de Colônias/uso terapêutico , Neoplasias/complicações , Neutropenia/epidemiologia , Neutropenia/prevenção & controle , Neutropenia/etiologia , Neutropenia/urina , Espanha/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Combinada/métodos , Quimioterapia CombinadaRESUMO
El 4-5% de las pacientes con cáncer de mama presentan metástasis oculares. Presentamos a una mujer de 30 años con un carcinoma ductal infiltrante de mama pT2N2M0 HER2 positivo. A los seis meses de finalizar el tratamiento presentó una recaída sistémica con múltiples localizaciones metástaticas por lo que inició tratamientos combinados de trastuzumab mantenido y quimioterapia. Tras 4 años con trastuzumab de mantenimiento presenta en iris de ojo derecho multiples micronódulos blanquecinos. Solo un 3-7.8% de las metástasis oculares se localizan en el iris. Con la terapia mantenida con trastuzumab la historia natural de la enfermedad avanzada ha cambiado, diversos estudios analizaron si existe mayor frecuencia de metástasis cerebrales en pacientes tratados con trastuzumab que en la era pretrastuzumab. La infrecuente aparición de metástasis en úvea anterior hace difícil establecer si es un hecho espontáneo o si está favorecido por el tratamiento con trastuzumab
The 4-5% of the breast cancer patients have metastases in the eye. We present the case of a 30-year-old woman with an infiltrant duct carcinoma of the breast pT2N2M0 HER2 positive. Six months after primary radical treatment she had a systemic relapse with multiples metastaticsites, so several treatment with trastuzumab in combination with chemotherapy were started. After 4 years patient presented multiple white-coloured micronodules in the iris of the right eye. Only a 3-7.8% of ocular metastases are located in the iris. With mantenaince therapy with trastuzumab natural history of the illness has changed. Several studies had analyzed if metastases in the brain during treatment with trastuzumab have increased in comparison with the pretrastuzumab era.The infrequent presentation of metastases in the anterior uveal makes difficult to establish if it is an spontaneous fact or if it is favoured by trastuzumab treatment