Phase II trial of humanized anti-Lewis Y monoclonal antibody for advanced hormone receptor-positive breast cancer that progressed following endocrine therapy

OBJECTIVES: The Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive BC after administration of endocrine therapy (ET). METHODS: A single-arm phase II study was conducted in seven centers. Patients with advanced hormone receptor-positive BC who failed first-line ET were included. The inclusion criterion was the observation of tumoral expression of the Lewis Y antigen during immunohistochemistry. The treatment comprised hu3S193 antibody administration at weekly intravenous doses of 20 mg/m2 for 8-week cycles. The primary endpoint was the clinical benefit rate. ClinicalTrials.gov NCT01370239. RESULTS: The study stopped accrual following an unplanned interim analysis as the hu3S193 antibody lacked sufficient activity to justify continuation of the study. Twenty-two patients were enrolled, of whom 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting with stable disease after 24 weeks. One patient with prolonged stable disease received medication for over 2 years. No partial or complete responses were observed. The median time to progression and overall survival was 5.4 and 37.5 months, respectively. CONCLUSIONS: The humanized anti-Lewis Y monoclonal antibody, hu3S193, exhibited insufficient activity in this cohort. However, the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression cannot be overlooked.

Mammary adenectomy followed by immediate reconstruction for treatment of patients with early-infiltrating breast carcinoma: a cohort study

ABSTRACT BACKGROUND: Use of mammary adenectomy for breast carcinoma treatment remains controversial. OBJECTIVE: This study aimed to verify the oncological safety of mammary adenectomy and immediate breast reconstruction for treating selected patients with infiltrating breast carcinoma and to evaluate patients' satisfaction with the reconstructed breasts. DESIGN AND SETTING: Cohort study conducted among patients treated at Hospital Sírio-Libanês, São Paulo, Brazil. METHODS: This study was based on 152 selected patients (161 operated breasts) with infiltrating breast carcinoma who underwent mammary adenectomy and immediate breast reconstruction. In all patients, the diameter of the largest focus of the tumor was less than 3.0 cm, the imaging tumor-nipple distance was greater than 2.0 cm and the pathological assessment showed clear margins. The cumulative incidence of local recurrence (LR), recurrence-free survival (RFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. After at least one year of follow-up, 64 patients were asked about their satisfaction with the reconstructed breast(s). RESULTS: At a mean follow-up time of 43.5 months, seven cases of LR (4.4%), four distant metastases (2.6%) and five deaths (3.3%) were recorded. The five-year actuarial LR-free survival, RFS and OS were 97.6%, 98.3% and 98.3%, respectively. No cases of nipple-areolar complex recurrence were reported. Forty-one patients (64%) indicated a high level of satisfaction with the reconstructed breasts. CONCLUSIONS: Mammary adenectomy is a safe and efficacious procedure for selected patients with early-infiltrating breast carcinoma and results in a high rate of patient satisfaction with the reconstructed breasts.

Quimioterapia em câncer de mama / Chemotherapy for breast cancer

Em 2010, um milhão e meio de mulheres receberão o diagnóstico de câncer de mama no mundo, sendo 49.000 no Brasil. O câncer de mama e uma área em constante evolução, exigindo, tanto da parte de mastologistas quanto dos oncologistas, rápida adaptação aos novos conceitos. Sabe-se que o câncer de mama não e uma doença única e, portanto, seu tratamento deve ser individualizado. A quimioterapia é uma parte importante do tratamento desta doença e tem evoluído recentemente, juntamente com a cirurgia, hormonioterapia, radioterapia e outros tratamentos de suporte, fazendo com que a mortalidade por esta doença continue a diminuir. Baseado em dados dos estudos de perfil molecular, e possível que mais de 50% das pacientes recebam quimioterapia adjuvante desnecessariamente. Revisa-se aqui o papel dos novos testes de perfil molecular disponíveis e o estado atual do uso de quimioterapia no câncer de mama. Nesta revisão, e dado especial enfoque ao tratamento adjuvante e neoadjuvante, sendo descritas algumas particularidades como o tratamento das pacientes idosas, da doença HER-2 positiva e da doença metastática.

In 2010, one and a half million women will be diagnosed with breast cancer worldwide, and 49, 000 in Brazil. Breast cancer is a constantly evolving area requiring from Mastologists and Oncologists a fast adaptation to new concepts. Furthermore, breast cancer does not consist of a single entity, therefore, it requires individualized treatment approaches. Chemotherapy is an important treatment modality, and it has been a rapidly evolving area that has been contributing to the decreasing breast cancer mortality observed in recent years, along with surgery, hormone therapy, radiotherapy, and other supportive treatments. Based on data from molecular profiling studies, more than 50% of the patients may be receiving unnecessary adjuvant chemotherapy. We aim to review the role of new molecular profiling tests and the current state of art in chemotherapy treatment for breast cancer. We also address the important issue of chemotherapy treatment in elderly patients, and the management of HER -2 positive and metastatic disease.

Inibidores da angiogênese e seus efeitos cardiovasculares no paciente com câncer: importância do manejo multidisciplinar / Angiogenesis inhibitors and cardiovascular adverse effects in cancer patients: the importance of multidisciplinary management

A angiogênese tem papel fundamental no crescimento tumoral. Células neoplásicas secretam fator de crescimento do endotélio vascular (vascular endothelial growthfactor - VEGF-A), estímulo para formação de nova vascularização, que promove suprimento sanguíneo às células tumorais e permite seu crescimento, invasão e metastatização. Os inibidores da angiogênese agem por meio da ligação inibitória ao VEGF (bevacizumabe) ou bloquando o receptor do VEGF-A (sunitinibe e sorafenibe). Seus efeitos antiangiogênicos incluem regressão e inibição da formação de neovasos. Essas medicações atualmente têm ampla utilização em terapias oncológicas. São agentes comercializados pela primeira vez em câncer colorretal metastático (becacizumabe) em 2004, mas que vêm desde então expandindo suas indicações: câncer de pulmão metastático (2006), carcinoma de células renais (2006), câncer de mama metastático (2008), glioblastoma multiforme recidivado (2008) e hepatocarcinoma avançado (2008). estudos atuais investigam o impacto da introdução desses agentes de maneira cada vez mais precoce na evolução da doença. Com isso, aumentam o tempo de exposição dos pacientes ao medicamento e o risco de seus efeitos colaterais. Viabiliza-se, portanto, o surgimento dos efeitos adversos tardios, até então pouco conhecidos, exigindo vigilância constante tanto clínica como epidemiológica. Os efeitos adversos...

Venous thromboembolism is a serious and potentially fatal disorder, which complicates the course of 20% of cancer patients, and has a significant impact on the quality of life and clinical outcomes of these patients. The pathophysiology of the association between thrombosis and cancer is complex. Malignancy is associated with a baseline hypercoagulable state secondary to the release of inflammatory cytokines, activation of the clotting system, expression of hemostatic proteins on tumor cells, inhibition of natural anticoagulants and impaired fibrinolysis. Several risk factors have been identified as contributing to venous thromboembolism and may be related to the patient characteristics, to the disease, and to the therapeutic interventions. The use of heparins and fondaparinux is indicated for selected cancer patients according to the types of malignancies and treatments. The treatment of venous thromboembolism in patients with cancer is challenging: the complications associated with the use of anticoagulants are significantly higher, may interfere with anticancer therapy and have a negative impact on quality of life.

Extensive deep vein thrombosis as a complication of testicular cancer treated with the BEP protocol (bleomycin, etoposide and cisplatin): case report

CONTEXT: There are no reports in the literature of massive deep venous thrombosis (DVT) associated with cisplatin, bleomycin and etoposide (BEP) cancer treatment. CASE REPORT: The patient was a 18-year-old adolescent with a nonseminomatous germ cell tumor of the right testicle, with the presence of pulmonary, liver, and massive retroperitoneal metastases. Following radical orchiectomy, the patient started chemotherapy according to the BEP protocol (without routine prophylaxis for DVT). On day 4 of the first cycle, massive DVT was diagnosed, extending from both popliteal veins up to the thoracic segment of the inferior vena cava. Thrombolytic therapy with streptokinase was immediately started. On day 2 of thrombolytic therapy, the patient developed acute renal failure, due to extension of the thrombosis to the renal veins. Streptokinase was continued for six days and the outcome was remarkably favorable.

CONTEXTO: Não há relatos na literatura de trombose venosa profunda (TVP) extensa associada ao protocolo de quimioterapia cisplatina, bleomicina e etoposite (BEP). RELATO DO CASO: O paciente era um adolescente de 18 anos com um tumor germinativo não-seminomatoso no testículo direito, com metástases pulmonares, hepáticas e retroperitoneais. Após orquiectomia radical, o paciente começou a receber quimioterapia de acordo com o protocolo BEP (sem profilaxia rotineira para TVP). No quarto dia do ciclo, TVP massiva foi diagnosticada, estendendo-se das veias poplíteas até o segmento inferior da veia cava torácica. Tratamento trombolítico foi iniciado imediatamente com estreptoquinase. No segundo dia da terapia trombolítica, o paciente desenvolveu insuficiência renal aguda, devido ao acometimento das veias renais pela trombose. Estroptoquinase foi mantida por seis dias e o paciente teve evolução surpreendentemente favorável.