RESUMO
Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the interdisciplinary approach to the treatment of deep infiltrating endometriosis. Endometriosis has been defined as the presence of endometrial glands and stroma outside the internal epithelial lining of the cavum uteri. As a consequence, endometriosis can cause a wide range of symptoms such as chronic pelvic pain, subfertility, dysmenorrhea, deep dyspareunia, cyclical bowel or bladder symptoms (e.g., dyschezia, bloating, constipation, rectal bleeding, diarrhoea and hematuria), abnormal menstrual bleeding, chronic fatigue or low back pain. Approx. 50â% of teenagers and up to 32â% of women of reproductive age, operated for chronic pelvic pain or dysmenorrhoea, suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, a causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The correct treatment for each patient should take into account the severity of the disease and whether the patient desires to have children. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 and > 60â% and is very much dependent on the integrated management and surgical skills of the respective hospital. Consequently, to optimise the individual patient's treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should, especially in the case of deep infiltrating endometriosis, be undertaken in appropriate centres.
Assuntos
Endometriose/diagnóstico , Endometriose/terapia , Comunicação Interdisciplinar , Colaboração Intersetorial , Endometriose/complicações , Endometriose/patologia , Feminino , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/patologia , Infertilidade Feminina/terapia , Prognóstico , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: The progesterone-receptor (PR) antagonists onapristone (type I) and mifepristone (type II) showed modest activity in hormone-receptor-positive breast cancer; however, onapristone in particular was associated with hepatotoxicity. Lonaprisan is a novel, type III PR antagonist that was well tolerated in phase I studies. PATIENTS AND METHODS: This randomized, open-label, phase II study evaluated the efficacy and tolerability of lonaprisan as second-line endocrine therapy in postmenopausal women with stage IV, PR-positive, HER2-negative, metastatic breast cancer. RESULTS: Patients received once-daily lonaprisan 25 mg (n = 34) or 100 mg (n = 34). The primary objective was not met (≥ 35% clinical benefit rate: complete/partial responses at any time until month 6 or stable disease [SD] for ≥ 6 months from start of treatment). There were no complete/partial responses. In the 25 mg and 100 mg groups, 6 of 29 patients (21%) and 2 of 29 patients (7%), respectively, had SD ≥ 6 months. Overall, 61 of 68 patients (90%) had ≥ 1 adverse event (AE), the most frequent (≥ 10% overall) being fatigue, hot flush, dyspnoea, nausea, asthenia, headache, constipation, vomiting, and decreased appetite; 33 patients had serious AEs. CONCLUSION: Lonaprisan showed limited efficacy as second-line endocrine therapy in postmenopausal women with PR-positive metastatic breast cancer.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estrenos/uso terapêutico , Receptores de Progesterona/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Estrenos/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Receptores de Progesterona/metabolismo , Resultado do TratamentoRESUMO
Local treatment of breast cancer with tumor-free surgical margins is the standard procedure in the treatment of T1 and small T2 breast cancers. Surgery is followed by radiation therapy, and adjuvant systemic therapy is offered depending on primary tumor characteristics, such as tumor size, grade of differentiation, number of involved axillary lymph nodes, the status of estrogen (ER) and progesterone (PR) receptors, and the expression of the human epidermal growth factor 2 (HER2) receptor. Although this approach implies a higher risk of ipsilateral breast tumor recurrence, the total risk of recurrence is low (1% per year), with rates of overall survival similar to that after radical procedures. The most peripheral part of epithelial tumors, the tumor margin, is the part which is most likely to remain in loco after surgical resection. Thus, understanding the biology of the invasion front is important as these tumor cells have been reported to lose epithelial properties, such as cohesiveness and keratin expression, and to acquire features of mesenchymal cells. The parallel appearance of tumor cells in different states of cell dedifferentiation implicates a dynamic equilibrium that is determined by the induction of epithelial-mesenchymal transition (EMT). EMT has been suggested to be of prime importance for tissue and vessel invasion. Furthermore, features of EMT are associated with the activity of tumor stem cells (TSC). TSC exist in breast cancer and their appearance varies depending on the used marker profile. Consequently, intratumoral heterogeneity is reflected by the grade of EMT activation. A specific function at the invasion front is hypothesized but has not yet been proven. Nevertheless, the molecular differentiation between the tumor center and the invasion front enhances the importance of tumor-free surgical margins.
Assuntos
Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/cirurgia , Mastectomia/métodos , Recidiva Local de Neoplasia/prevenção & controle , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Carcinoma Lobular/terapia , Quimioterapia Adjuvante , Terapia Combinada , Diagnóstico por Imagem , Transição Epitelial-Mesenquimal , Feminino , Humanos , Imuno-Histoquímica/métodos , Excisão de Linfonodo , Metástase Linfática , Modelos Biológicos , Invasividade Neoplásica , Proteínas de Neoplasias/análise , Células-Tronco Neoplásicas/química , Células-Tronco Neoplásicas/patologia , Radioterapia Adjuvante , Risco , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/cirurgiaRESUMO
BACKGROUND: Hormone receptor-positive advanced breast cancer is an increasing health burden. Although endocrine therapies are recognised as the most beneficial treatments for patients with hormone receptor-positive advanced breast cancer, the optimal sequence of these agents is currently undetermined. METHODS: We reviewed the available data on randomised controlled trials (RCTs) of endocrine therapies in this treatment setting with particular focus on RCTs reported over the last 15 years that were designed based on power calculations on primary end points. RESULTS: In this paper, data are reviewed in postmenopausal patients for the use of tamoxifen, aromatase inhibitors and fulvestrant. We also consider the available data on endocrine crossover studies and endocrine therapy in combination with chemotherapy or growth factor therapies. Treatment options for premenopausal patients and those with estrogen receptor-/human epidermal growth factor receptor 2-positive tumours are also evaluated. CONCLUSION: We present the level of evidence available for each endocrine agent based on its efficacy in advanced breast cancer and a diagram of possible treatment pathways.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismoRESUMO
BACKGROUND: An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory. METHODS: Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m(-2) plus vinorelbin 25 mg m(-2) on days 1+8 (GemVin), or plus cisplatin 30 mg m(-2) on days 1+8 (GemCis), or plus capecitabine 650 mg m(-2) b.i.d. orally days 1-14 (GemCap), q3w. The primary end point was response rate. RESULTS: A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ≥grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand-foot syndrome in 2.0% of the GemCap patients (per patient analysis). CONCLUSIONS: This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Capecitabina , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , GencitabinaRESUMO
PURPOSE: To determine the value of a breast ultrasound (US) examination in addition to mammography in cases of American College of Radiology (ACR) tissue pattern III and IV in symptomatic women and women at risk. MATERIALS AND METHODS: A prospective cohort was initiated between 2001 and 2005 with a total of 59,514 patients and 102,744 mammograms. Documentation was available for 102,557 diagnostic procedures. Breast US was indicated in all women with ACR III and IV in addition to a suspicious clinical examination and in cases of masses and focal asymmetries in mammography. RESULTS: In total, 62,006 additional USs were performed, in which 116 mammographically and clinically occult breast cancers were diagnosed (detection rate: 1.9/1,000 examinations), while mammography alone (40,551 examinations) revealed 903 cancers (22.3/1,000). Of all 1,019 breast cancer findings, 12.8% were detected because of the combination of mammography and US. In the group with ACR III/IV, 15.9% of cancers were found by supplemental US compared with mammography alone. CONCLUSION: The addition of US to mammography vs. mammography alone resulted in a significant (P < 0.01) increase in breast cancer detection rate.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Garantia da Qualidade dos Cuidados de Saúde , Ultrassonografia Mamária , Adulto , Idoso , Algoritmos , Neoplasias da Mama/epidemiologia , Distribuição de Qui-Quadrado , Diagnóstico Diferencial , Feminino , Alemanha/epidemiologia , Humanos , Mamografia , Pessoa de Meia-Idade , Exame Físico , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: The analysis of cost effectiveness in hospitals is as difficult as treating the patients properly. We are yet not able to answer the simple question of what costs are caused by a certain diagnosis and its treatment during an average hospital stay. METHODS: To answer some issues of the global problem of cost effectiveness during hospitalisation, we analysed the costs and the cost structure of a normal obstetrical hospital stay during an uncomplicated vaginal delivery and a planned caesarean section. Cost data was collected and summarized from the patients file, the hospital's computer system gathering all cost centres, known material expenses and expenses of non obstetrical medical services. RESULTS: For vaginal deliveries/planned caesareans we can calculate with a surplus of about 83Euro/1432Euro. About 45% of the summarized costs are calculated on a reliable database. DISCUSSION: The introduction of the DRG based clearing system in Germany has aggravated the discussion on cost effectiveness. Our meticulous work-up of expenses excluded personal precautionary costs and personnel costs of documentation because no tools are described to depict such costs. If we would add these costs to the known expenses of our study, we strongly suspect that hospital treatment of vaginal deliveries or planned caesarean sections is not cost effective.
Assuntos
Cesárea/economia , Parto Obstétrico/economia , Hospitalização/economia , Adolescente , Adulto , Análise Custo-Benefício , Custos e Análise de Custo , Grupos Diagnósticos Relacionados , Feminino , Humanos , Corpo Clínico Hospitalar/economia , Gravidez , Adulto JovemRESUMO
Investigation of high-dose chemotherapy (HD-CT) compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and >/=10 axillary lymph nodes. From November 1993 to September 2000, 307 patients were randomized to receive after four cycles of epirubicin (90 mg/m(2)), cyclophosphamide (600 mg/m(2)) i.v. (every 21 days) and either HD-CT of cyclophosphamide (1500 mg/m(2)), thiotepa (150 mg/m(2)) and mitoxantrone (10 mg/m(2)) i.v. for four consecutive days followed by stem cell transplantation or a SD-CT of three cycles CMF (cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), 5-fluorouracil 600 mg/m(2), i.v. on day 1 and 8, respectively, every 28 days). After a median follow-up of 6.1 years, 166 events with respect to event-free survival (EFS) (SD-CT: 91, HD-CT: 75) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0.80 [95% confidence interval (0.59, 1.08)], P = 0.15. The trend to a superiority of HD-CT as compared with SD-CT with respect to EFS seems to be more pronounced in premenopausal patients as compared with postmenopausal patients and in patients with tumor grade 3 as compared with patients with tumor grade 1/2. With a follow-up of 6 years, there was a trend in favor of HD-CT with respect to EFS not being significant. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients who might benefit from HD-CT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas , Linfonodos/patologia , Adulto , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Estadiamento de Neoplasias , Estudos Prospectivos , Análise de Sobrevida , Tiotepa/administração & dosagem , Transplante AutólogoRESUMO
Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.
Assuntos
Difosfonatos/uso terapêutico , Neoplasias/tratamento farmacológico , Osteoporose/prevenção & controle , Guias de Prática Clínica como Assunto , Antineoplásicos/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Neoplasias da Mama/terapia , Carcinoma/secundário , Carcinoma/terapia , Feminino , Humanos , Neoplasias Renais/terapia , Neoplasias Pulmonares/terapia , Masculino , Neoplasias/complicações , Osteonecrose/prevenção & controle , Osteoporose/etiologia , Neoplasias da Próstata/terapiaRESUMO
PURPOSE: To examine factors associated with one step surgery in case of non-palpable breast cancer. MATERIALS AND METHODS: Clinical data of 152 consecutively diagnosed patients with breast cancer were analyzed retrospectively. Preoperative diagnostic findings were divided in subgroups: mammographically visible mass/microcalcifications/sonographically visible mass/sonographically visible architectural distortion. Correlation between tumor-size, radiologic tumor morphology, quality of localization and number of operation was evulated. For localization exact wire position was defined less than 3mm apart from the lesion. RESULTS: One hundred and thirty-six patients attempted breast conservation and underwent preoperative tumor localization. Fourteen of 16 patients had mastectomy without preoperative localization. Average tumor size was 12mm for one-operation, and 17mm for re-operation. Significant correlation (p<0.001) was found between one operation and masses visible in mammograms (55/62 (89%) patients) or sonography (53/64 (83%) patients). Significant correlation was found (p<0.001) between more re-operation and microcalcifications in mammograms (33/89 (37% patients). In 123/138 (89%) cases wire position was central, in 15/138 (11%) cases distance was maximally 10mm. No significant correlation was found between number of operation and wire position. Re-operation was required in 38 cases. CONCLUSION: Mammographically or sonographically visible mass, small size of tumors, preoperative percutaneous biopsy and exact preoperative localization are important for a single step procedure for definite surgical treatment, that we found in 74% of the patients.
Assuntos
Neoplasias da Mama/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Neoplasias da Mama/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Carcinoma in Situ/diagnóstico por imagem , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Mamografia/métodos , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Palpação , Radiografia Intervencionista , Reoperação , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Técnicas Estereotáxicas , Ultrassonografia de Intervenção , Ultrassonografia Mamária/métodosAssuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Antígeno Ki-67/metabolismo , Neoplasias Hormônio-Dependentes/diagnóstico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Técnicas de Diagnóstico Molecular , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/patologia , Valor Preditivo dos Testes , Coloração e Rotulagem , Tamoxifeno/uso terapêutico , Resultado do TratamentoRESUMO
We report on a family in which a daughter is described with mental retardation, as well as malformations of the heart, and of the brain (Dandy-Walker variant). The patient's phenotype suggests a chromosomal rearrangement. However, her karyotype was unremarkable by conventional cytogenetic analysis. In order to detect chromosome rearrangements overseen by this method, the subtelomere regions of suspicious chromosomes were verified by fluorescence in situ hybridization (FISH). A rearranged derivative chromosome 6 was identified. Further examinations by FISH-microdissection (FISH-MD) revealed a maternal complex balanced translocation. The patient inherited the derivative chromosome 6 from her mother and therefore carries a partial monosomy 6q26-->qter and a partial trisomy 11q23.3-->qter.
Assuntos
Desequilíbrio Alélico , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 6 , Translocação Genética , Aberrações Cromossômicas , Mapeamento Cromossômico , Dissecação/métodos , Feminino , Humanos , Hibridização in Situ Fluorescente , Mães , Telômero/genéticaRESUMO
PURPOSE: The majority of breast cancers are diagnosed at an early stage, and treatment is focused on cure and prolonging disease-free survival. Local therapy (surgery and/or radiation treatment) is standard, along with systemic adjuvant therapy that may effectively prevent or delay relapse and death in early-stage disease. In premenopausal women, adjuvant therapeutic approaches include combination cytotoxic chemotherapy and endocrine therapy. Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) was the established chemotherapy regimen; however, newer regimens have more recently been introduced that may offer some benefit over CMF including anthracycline-containing regimens [e.g. cyclophosphamide, epirubicin and 5-fluorouracil (CEF)], and taxane-containing regimens. For women with oestrogen receptor (ER)-positive disease, a second option is endocrine therapy that aims to suppress mitogenic oestrogen signalling. Until recently, 5 years of tamoxifen was regarded as the standard adjuvant endocrine treatment in ER-positive disease. Ovarian ablation is also effective in premenopausal women, and can be achieved by surgery, radiotherapy, or via the use of a luteinising hormone-releasing hormone analogue such as goserelin. Combining tamoxifen and goserelin treatment provides more effective oestrogen blockade than either drug alone. However, as the third-generation aromatase inhibitors (AIs) have demonstrated improved efficacy over tamoxifen in postmenopausal women with early and advanced disease, combination treatment with goserelin plus an AI may provide optimal oestrogen blockade in premenopausal patients. CONCLUSIONS: This review assesses the relative merits of chemotherapeutic and endocrine approaches for the treatment of early breast cancer, and summarises relevant ongoing clinical trials, with an emphasis on the premenopausal setting.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Tratamento Farmacológico/tendências , Pré-Menopausa , Neoplasias da Mama/patologia , Carcinoma/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/patologia , Ovário/efeitos dos fármacos , Satisfação do Paciente , Pré-Menopausa/efeitos dos fármacos , Qualidade de VidaRESUMO
Estrogen receptors (ER's) were determined by agar gel electrophoresis in 105 human mammary tumor biopsies. Fifty-three tumor specimens revealed measurable amounts of receptor, and 64% of these patients showed an objective remission after endocrine treatment. If we also include cases with partial remission, previous response, and arrested growth but no actual remission, the benefit rate increases to 87%. The corresponding percentage in the ER-negative groups is 13%. In a retrospective study of 42 patients with human breast cancer, a correlation between ER finding and remission rate after chemotherapy was found. Of the ER-negative patients, 71% showed an objective remission after polychemotherapy, whereas only 43% of the ER-positive cases revealed such remission. The presented data are discussed with special regard to their clinical relevance.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias Hormônio-Dependentes/metabolismo , Receptores de Estrogênio , Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Quimioterapia Combinada , Glândulas Endócrinas/efeitos dos fármacos , Glândulas Endócrinas/cirurgia , Feminino , Humanos , Neoplasias Hormônio-Dependentes/terapia , Remissão EspontâneaRESUMO
A new estrogen receptor immunocytochemical assay (ER-ICA) which uses monoclonal antibodies to the estrogen receptor protein was applied to 97 breast cancer tissues. The results were correlated to those obtained by conventional dextran coated charcoal assays. The presence or absence of nuclear staining was significantly associated with positive or negative estrogen receptor status by dextran-coated charcoal (P less than 0.001). Furthermore ER-ICA results showed a high degree of correlation with a light microscopic grading. The relationship between ER-ICA results and response to endocrine therapies in patients with advanced disease was assessed in 20 patients. Six of 11 (55%) ER-ICA positive patients responded, whereas 8 of 9 (89%) ER-ICA negative patients failed.
Assuntos
Neoplasias da Mama/análise , Receptores de Estrogênio/análise , Anticorpos Monoclonais , Carvão Vegetal , Dextranos , Feminino , Histocitoquímica , Humanos , Técnicas ImunoenzimáticasRESUMO
Blood levels of transforming growth factor beta 2 (TGF-beta 2) were measured in 20 patients with metastatic breast cancer before and during treatment with the antiestrogen tamoxifen, and in a control group of 7 patients with primary breast cancer before and during adjuvant tamoxifen treatment. The results of this study reveal typical time patterns for TGF-beta 2 in relation to the clinical outcome. Patients in remission showed a significant increase of TGF-beta 2 in the first 4-6 weeks of therapy, followed by a subsequent decrease. Patients who did not respond showed unchanged or diminished TGF-beta 2 values after start of therapy, followed by a later increase preceding the clinical manifestation of tumor progression. Thus, TGF-beta 2 blood levels after 4 weeks of tamoxifen treatment can be used as an early marker for prediction of response.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Antagonistas de Estrogênios/uso terapêutico , Tamoxifeno/uso terapêutico , Fator de Crescimento Transformador beta/sangue , Neoplasias da Mama/diagnóstico , Humanos , Metástase Neoplásica , Prognóstico , Receptores de Estrogênio/análise , Receptores de Progesterona/análiseRESUMO
PURPOSE: To compare quality of life (QoL) in premenopausal and perimenopausal patients with node-positive, early breast cancer treated with the endocrine agent goserelin (Zoladex; AstraZeneca Pharmaceuticals LP, Wilmington, DE) or cyclophosphamide + methotrexate + fluorouracil (CMF). PATIENTS AND METHODS: Patients from 86 centers worldwide were randomly assigned to receive either goserelin (3.6 mg every 28 days for 2 years; n = 514) or CMF (six 28-day cycles; n = 496), and were included in the QoL study. QoL was assessed using a self-administered patient questionnaire that consisted of 39 items from the Rotterdam Symptom Checklist, including dimensions evaluating physical and psychological symptom distress, activities of daily living, hormonal effects, and an assessment of overall QoL. RESULTS: Early benefits were noted during months 3 to 6 of treatment, for goserelin compared with CMF. Significant differences were found for changes in overall QoL (eg, 6.96 +/- 0.88 v 0.69 +/- 0.92 at 6 months; P <.0001) and for physical symptom distress, activity levels, and "effort to cope with illness" dimensions. At 1, 2, and 3 years, there were no significant differences in overall QoL or specific QoL dimensions. Scores for hormonal symptoms were worse with goserelin during the 2-year goserelin treatment period; however, this trend was reversed at 3 years. CONCLUSION: Goserelin offers improved overall QoL during the first 6 months of therapy compared with CMF chemotherapy in premenopausal and perimenopausal patients with early breast cancer. Coupled with equivalent efficacy in estrogen receptor-positive patients, these data support the use of goserelin as an alternative to CMF in premenopausal and perimenopausal patients with estrogen receptor-positive, node-positive early breast cancer.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Gosserrelina/uso terapêutico , Qualidade de Vida , Adulto , Neoplasias da Mama/patologia , Climatério , Ciclofosfamida/administração & dosagem , Análise Fatorial , Feminino , Fluoruracila/administração & dosagem , Humanos , Metástase Linfática , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Pré-Menopausa , Inquéritos e QuestionáriosRESUMO
Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.
Assuntos
Androstenodiona/análogos & derivados , Antineoplásicos/uso terapêutico , Inibidores da Aromatase , Neoplasias da Mama/tratamento farmacológico , Menopausa , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstenodiona/efeitos adversos , Androstenodiona/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias da Mama/enzimologia , Neoplasias da Mama/metabolismo , Avaliação de Medicamentos , Estradiol/sangue , Feminino , Alemanha Ocidental , Humanos , Tábuas de Vida , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Receptores de Estrogênio/metabolismo , Indução de Remissão , Tamoxifeno/uso terapêuticoRESUMO
One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Busserrelina/análogos & derivados , Menopausa , Adulto , Busserrelina/administração & dosagem , Busserrelina/efeitos adversos , Busserrelina/uso terapêutico , Preparações de Ação Retardada , Feminino , Gosserrelina , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Metástase Neoplásica , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Indução de RemissãoRESUMO
PURPOSE: To compare the efficacy and tolerability of anastrozole (1 and 10 mg once daily), a selective, oral, nonsteroidal aromatase inhibitor, and megestrol acetate (40 mg four times daily), in postmenopausal women who progressed following tamoxifen treatment. PATIENTS AND METHODS: Two randomized, double-blind for anastrozole, open-label for megestrol acetate, parallel-group, multicenter trials were conducted in 764 patients. Because both trials were identical in design, an analysis of the combined results was performed to strengthen interpretation of results from each trial. RESULTS: The median follow-up duration was approximately 6 months. The estimated progression hazards ratios were 0.97 (97.5% confidence interval [CI], 0.75 to 1.24) for anastrozole 1 mg versus megestrol acetate and 0.92 (97.5% CI, 0.71 to 1.19) for anastrozole 10 mg versus megestrol acetate. The overall median time to progression was approximately 21 weeks. Approximately one third of patients in each group benefited from treatment. Twenty-seven patients (10.3%) in the anastrozole 1-mg group, 22 (8.9%) in the anastrozole 10-mg group, and 20 (7.9%) in the megestrol acetate group had a complete or partial response, and 66 (25.1%), 56 (22.6%), and 66 (26.1%) patients, respectively, had stable disease for > or = 24 weeks. For all end points, individual trial results were similar to the results of the combined analysis. Anastrozole and megestrol acetate were well tolerated. Gastrointestinal disturbance was more common among patients in the anastrozole groups than the megestrol acetate group; the difference between the anastrozole 10 mg and megestrol acetate groups was significant (P = .005). Significantly fewer patients in the anastrozole 1-mg (P < .0001) and 10-mg (P < .002) groups had weight gain than in the megestrol acetate group. More than 30% of megestrol acetate-treated patients had weight gain > or = 5%, and 10% of patients had weight gain > or = 10%. Patients who received megestrol acetate continued to gain weight over time. CONCLUSION: Anastrozole, 1 and 10 mg once daily, is well tolerated and as effective as megestrol acetate in the treatment of postmenopausal women with advanced breast cancer who progressed following tamoxifen treatment. Moreover, anastrozole therapy avoids the weight gain associated with megestrol acetate treatment.