Assuntos
Neoplasias da Mama/terapia , Congressos como Assunto , Áustria , Feminino , Humanos , SuíçaRESUMO
Breast cancer has become curable for the majority of women in Western Europe and North America. Advances have been made in imaging diagnostics as well as the implementation of nationwide screening programmes. Nowadays, we talk about prevention as well as treatment. Pathology has moved from pure morphology (tumour type, grade and stage) to biological characterisation of the tumour. Treatment has changed considerably through a better understanding of the disease; from a local disease predominated by extensive and mutilating surgical techniques to a point where breast cancer has come into its own as a systemic disease with equal "rights" to local as well as systemic treatment. This paradigm shift has led to a multidisciplinary approach of the understanding and treatment of breast cancer. Molecular classification has changed the understanding of breast cancer and will be the basis for an even more individualised treatment. New (biological) agents will help to further tailor treatment to response or resistance. While systemic treatment has been increased in number and duration surgical/local strategies have been reduced to minimum. Evidence-based medicine has helped to improve and standardise treatment of breast cancer. This review summarises the 10th Biedenkopf meeting that was held to review the advances in breast cancer understanding and treatment.
Assuntos
Neoplasias da Mama/terapia , Detecção Precoce de Câncer , Neoplasias da Mama/patologia , Medicina Baseada em Evidências , Feminino , Humanos , PesquisaRESUMO
With the continuing increase of median life expectancy of important segments of the world's population, cancer incidence, as well as cancer related morbidity and mortality, are constantly increasing, especially for developing countries and for breast and prostate cancer, the predominant gender-associated cancer types. In addition to continuing, with more and more expensive efforts to develop new and more effective cancer treatments, it is health-politically and medico-professionally important to realise that only successful approaches to primary cancer prevention of major and frequent cancer types will be able to change this socially and economically unfavourably outlook. It is therefore encouraging to see that primary (or pharmacologic, interventional) cancer prevention programs have been successfully developed over the past decade for individuals at elevated risk for breast and prostate cancer on the basis of several scientifically well-conducted, prospective chemoprevention trials, mainly with synthetic anti-hormones (anti-estrogens and anti-androgens) in the USA, in Europe and Australia. This paper summarises the presently published results and design of several completed and some currently running primary cancer prevention trials in breast cancer and prostate cancer, and also points to the important obstacles for their conduct and translation into general practice in the broader populations at risk outside of clinical prevention research.
RESUMO
PURPOSE: To provide guidance for clinicians about the diagnosis, staging and treatment of breast cancer occurring during an otherwise uncomplicated pregnancy. METHODS: An international expert Panel convened to address a series of questions identified by a literature review and personal experience. Issues relating to the diagnosis and management of breast cancer after delivery were outside the scope. RESULTS: There is a paucity of large and/or randomized studies. Based on cohort studies, case series and case reports, the recommendations represent the best available evidence, albeit of a lower grade than is optimal. RECOMMENDATIONS: In most circumstances, serious consideration should be given to the option of treating breast cancer whilst continuing with the pregnancy. Each woman should ideally be referred to a centre with sufficient expertise, given a clear explanation of treatment options. Most diagnostic and staging examinations can be performed adequately and safely during pregnancy. Treatment should however be adapted to the clinical presentation and the trimester of the pregnancy: surgery can be performed during all trimesters of pregnancy; radiotherapy can be considered during the first and second trimester but should be postponed during the third trimester; and standard chemotherapies can be used during the second and third trimester. Since neonatal morbidity mainly appears to be related to prematurity, delivery should not be induced before 37 weeks, if at all possible. CONCLUSIONS: The treatment of breast cancer in pregnancy should be executed by experienced specialists in a multidisciplinary setting and should adhere as closely as possible to standard protocols.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/terapia , Antineoplásicos/uso terapêutico , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Estadiamento de Neoplasias/métodos , Gravidez , Resultado da Gravidez , Cuidado Pré-Natal/métodos , Diagnóstico Pré-Natal/métodosRESUMO
Evidence clearly shows a chemopreventive effect for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably other cancer types; however, data on the risk-benefit profile for cancer prevention are insufficient and no definitive recommendations can be made. Aspirin has emerged as the most likely NSAID for use in chemoprevention because of its known cardiovascular benefit and available safety and efficacy data. Other traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now given to patients at high risk of colorectal cancer, although these drugs do not provide cardioprotection. More studies of aspirin and cancer prevention are needed to define the lowest effective dose, the age at which to initiate therapy, the optimum treatment duration, and the subpopulations for which the benefits of chemoprevention outweigh the risks of adverse side-effects. Although it might be possible to answer some of these questions with longer follow-up of existing clinical trials, randomised controlled trials with new study designs will be needed. Future projects should investigate the effects of aspirin treatment on multiple organ systems. Cancers of interest are colorectal, breast, prostate, lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers; therefore coadministration of aspirin with a proton-pump inhibitor is an attractive option and is under investigation in the AspECT trial.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neoplasias/prevenção & controle , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Neoplasias da Mama/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Neoplasias do Sistema Digestório/prevenção & controle , Feminino , Humanos , Neoplasias Pulmonares/prevenção & controle , Neoplasias Ovarianas/prevenção & controle , RiscoAssuntos
Neoplasias da Mama/enzimologia , Ciclo-Oxigenase 2/metabolismo , Androstadienos/uso terapêutico , Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Celecoxib , Inibidores de Ciclo-Oxigenase/uso terapêutico , Regulação para Baixo , Quimioterapia Combinada , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Pirazóis/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sulfonamidas/uso terapêutico , Falha de TratamentoAssuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Capecitabina , Cromogranina A/sangue , Desoxicitidina/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To evaluate and validate mRNA expression markers capable of identifying patients with ErbB2-positive breast cancer associated with distant metastasis and reduced survival. PATIENTS AND METHODS: Expression of 60 genes involved in breast cancer biology was assessed by quantitative real-time PCR (qrt-PCR) in 317 primary breast cancer patients and correlated with clinical outcome data. Results were validated subsequently using two previously published and publicly available microarray data sets with different patient populations comprising 295 and 286 breast cancer samples, respectively. RESULTS: Of the 60 genes measured by qrt-PCR, urokinase-type plasminogen activator (uPA or PLAU) mRNA expression was the most significant marker associated with distant metastasis-free survival (MFS) by univariate Cox analysis in patients with ErbB2-positive tumors and an independent factor in multivariate analysis. Subsequent validation in two microarray data sets confirmed the prognostic value of uPA in ErbB2-positive tumors by both univariate and multivariate analysis. uPA mRNA expression was not significantly associated with MFS in ErbB2-negative tumors. Kaplan-Meier analysis showed in all three study populations that patients with ErbB2-positive/uPA-positive tumors exhibited significantly reduced MFS (hazard ratios [HR], 4.3; 95% CI, 1.6 to 11.8; HR, 2.7; 95% CI, 1.2 to 6.2; and, HR, 2.8; 95% CI, 1.1 to 7.1; all P < .02) as compared with the group with ErbB2-positive/uPA-negative tumors who exhibited similar outcome to those with ErbB2-negative tumors, irrespective of uPA status. CONCLUSION: After evaluation of 898 breast cancer patients, uPA mRNA expression emerged as a powerful prognostic indicator in ErbB2-positive tumors. These results were consistent among three independent study populations assayed by different techniques, including qrt-PCR and two microarray platforms.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/análise , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Análise de Variância , Biomarcadores Tumorais/genética , Neoplasias da Mama/química , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Razão de Chances , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Regulação para Cima , Ativador de Plasminogênio Tipo Uroquinase/genéticaRESUMO
High serum concentrations of insulin-like growth factor-1 (IGF-1) are associated with an increased risk of breast, prostate, colorectal, and lung cancer whereas IGF binding protein-3 (IGFBP-3) seems to exert a protective effect. Therefore, patients may benefit from low IGF-1 levels and high IGFBP-3 levels. This study evaluated whether adjuvant anthracycline-containing chemotherapy modulates IGF-1 and/or IGFBP-3 serum levels in breast cancer patients. In 18 patients undergoing adjuvant treatment for primary breast cancer, IGF-1 and IGFBP-3 serum levels were measured with immunoassays during chemotherapy regimens of either 5-fluorouracil, epirubicin and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC). Mean pre-treatment values of IGF-1 and IGFBP-3 were 124+/-13 and 3698+/-186 ng/ml, respectively. No significant changes in IGF-1 and IGFBP-3 serum concentrations were observed during adjuvant anthracycline-containing chemotherapy. IGF-1 levels significantly correlated with IGFBP-3 levels before and during chemotherapy. In conclusion, these chemotherapy regimens do not seem to modulate IGF-1 or IGFBP-3 levels in a favourable or unfavourable way.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Pessoa de Meia-IdadeRESUMO
PURPOSE: Increasing numbers of older women are affected by early breast cancer, because of prolonged life expectancy and the increasing incidence of breast cancer with age. The role of adjuvant therapy for this population is still a matter of debate. We reviewed the long-term outcome of a mature trial comparing endocrine treatment versus no adjuvant therapy in older women with node-positive breast cancer. PATIENTS AND METHODS: From 1978 to 1981, 349 women 66 to 80 years of age with pathologically involved lymph nodes after total mastectomy and axillary clearance were randomly assigned to receive 12 months of adjuvant tamoxifen plus low-dose prednisone (p+T) or no adjuvant therapy. Three hundred twenty patients were eligible. RESULTS: At 21 years' median follow-up, 1 year of p+T significantly prolonged disease-free survival (DFS; P =.003) and overall survival (P =.05; 15-year DFS, 10% +/- 3% v 19% +/- 3%; hazard ratio, 0.71; 95% CI, 0.58 to 0.86). When comparing competing causes of failure (breast cancer recurrence and deaths before breast cancer recurrence), p+T was far superior in controlling breast cancer recurrence (P =.0003), but the improvement was seen mainly in soft tissue sites. Conversely, patients in the p+T group were more likely to die before a breast cancer recurrence (P =.03). CONCLUSION: This trial demonstrates that significant treatment benefits continue to be observed in older patients treated for 1 year with p+T. Despite issues relating to competing causes of failure, older breast cancer patients can benefit from treatment and should be considered for trials of adjuvant systemic therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Terapia Combinada , Seguimentos , Humanos , Masculino , Prednisona/administração & dosagem , Modelos de Riscos Proporcionais , Análise de Sobrevida , Tamoxifeno/administração & dosagem , Resultado do TratamentoRESUMO
This account of the highlights of the eighth St Gallen (Switzerland) meeting in 2003 emphasizes new information that has emerged during the 2 years since the seventh meeting in 2001. This article should be read in conjunction with the report of that earlier meeting. Recommendations for patient care are so critically dependent on assessment of endocrine responsiveness that the importance of high-quality steroid hormone receptor determination and standardized quantitative reporting cannot be overemphasized. The International Consensus Panel modified the risk categories so that only endocrine receptor-absent status was sufficient to reclassify an otherwise low-risk, node-negative disease into the category of average risk. Absence of steroid hormone receptors also was recognized as indicating endocrine nonresponsiveness. Some important areas highlighted at the recent meeting include: (1) recognition of the separate nature of endocrine-nonresponsive breast cancer-both invasive cancers and ductal carcinoma-in-situ; (2) improved understanding of the mechanisms of acquired endocrine resistance, which offer exciting prospects for extending the impact of successful sequential endocrine therapies; (3) presentation of high-quality evidence indicating that chemotherapy and tamoxifen should be used sequentially rather than concurrently; (4) availability of a potential alternative to tamoxifen for treatment of postmenopausal women with endocrine-responsive disease; and (5) the promise of newly defined prognostic and predictive markers.
Assuntos
Neoplasias da Mama/terapia , Cooperação Internacional , Neoplasias da Mama/patologia , Feminino , Guias como Assunto , Humanos , Metástase Linfática , Prognóstico , SuíçaRESUMO
Primary systemic therapy (PST) represents the standard of care in patients with locally advanced breast cancer. In addition, there is increasing information on PST in operable breast disease that supports the use of PST in routine practice. However, current regimens and techniques vary. To address this concern, a group of representatives from breast cancer clinical research groups in France, Germany, Italy, the United Kingdom, and the United States reviewed all available data on prospective randomized trials in this setting. Recommendations are made regarding terminology, indications, regimen, diagnosis before treatment, monitoring of efficacy, tumor localization, surgery, pathologic evaluation, and postoperative treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Medicina Baseada em Evidências , Feminino , Humanos , Cooperação Internacional , Terapia Neoadjuvante , Estadiamento de Neoplasias , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Interest in insulin-like growth factors (IGFs) and their effect on carcinogenesis has increased recently because high serum concentrations of IGF1 are associated with an increased risk of breast, prostate, colorectal, and lung cancers. Physiologically, IGF1 is the major mediator of the effects of the growth hormone; it thus has a strong influence on cell proliferation and differentiation and is a potent inhibitor of apoptosis. The action of IGF1 is predominantly mediated through the IGF1 receptor (IGF1R). IGF1R is involved in several oncogenic transformation processes. The availability of unbound IGF1 for interaction with IGF1R is modulated by IGF-binding proteins (IGFBP1-6). IGFBPs, especially IGFBP3, have independent effects on cell growth, for example, IGFBP3 has proapoptotic activities both dependent on and independent of p53.