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Among the potential adverse effects of breast cancer treatment, chemotherapy-related cognitive impairment (CRCI) has gained increased attention in the past years. In this review, we provide an overview of the literature regarding CRCI in breast cancer, focusing on three main aspects. The first aspect relates to the molecular mechanisms linking individual drugs commonly used to treat breast cancer and CRCI, which include oxidative stress and inflammation, reduced neurogenesis, reduced levels of specific neurotransmitters, alterations in neuronal dendrites and spines, and impairment in myelin production. The second aspect is related to the clinical characteristics of CRCI in patients with breast cancer treated with different drug combinations. Data suggest the incidence rates of CRCI in breast cancer vary considerably, and may affect more than 50% of treated patients. Both chemotherapy regimens with or without anthracyclines have been associated with CRCI manifestations. While cross-sectional studies suggest the presence of symptoms up to 20 years after treatment, longitudinal studies confirm cognitive impairments lasting for at most 4 years after the end of chemotherapy. The third and final aspect is related to possible therapeutic interventions. Although there is still no standard of care to treat CRCI, several pharmacological and non-pharmacological approaches have shown interesting results. In summary, even if cognitive impairments derived from chemotherapy resolve with time, awareness of CRCI is crucial to provide patients with a better understanding of the syndrome and to offer them the best care directed at improving quality of life.

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The excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1. In this analysis, the incidence of grade 3-4 left ventricular systolic dysfunction (LVSD) in T-DM1 or trastuzumab plus paclitaxel arms were respectively 0.8 and 1.8%. In addition, three (0.8%) patients in the T-DM1 arm and six (5.3%) patients in the adjuvant paclitaxel with trastuzumab (TH) arm experienced a significant asymptomatic left ventricular ejection fraction (LVEF) decline that per-protocol required holding T-DM1 or trastuzumab. All patients with available follow-up data experienced full resolution of cardiac symptoms and LVEF normalization. Furthermore, we performed an exploratory analysis to assess the relationship between age, baseline LVEF, and body mass index with cardiac outcomes. No significant association between these baseline characteristics and the incidence of significant asymptomatic LVEF decline or symptomatic LVSD was identified. The low incidence of significant cardiac adverse events in this population during therapy with adjuvant T-DM1 suggests that studies on the cost-effectiveness of cardiac monitoring during adjuvant therapy using anthracycline-free regimens are needed.Clinical Trial Registration: ClinicalTrials.gov, NCT01853748.

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BACKGROUND: This is an updated version of the original Cochrane review published in The Cochrane Library 2009, Issue 3. Most women with early cervical cancer (stages I to IIA) are cured with surgery or radiotherapy, or both. We performed this review originally because it was unclear whether cisplatin-based chemotherapy after surgery, radiotherapy or both, in women with early stage disease with risk factors for recurrence, was associated with additional survival benefits or risks. OBJECTIVES: To evaluate the effectiveness and safety of platinum-based chemotherapy after radical hysterectomy, radiotherapy, or both in the treatment of early stage cervical cancer. SEARCH METHODS: For the original 2009 review, we searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, LILACS, BIOLOGICAL ABSTRACTS and CancerLit, the National Research Register and Clinical Trials register, with no language restriction. We handsearched abstracts of scientific meetings and other relevant publications. We extended the database searches to November 2011 for this update. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy (after radical surgery, radiotherapy or both) with no adjuvant chemotherapy, in women with early stage cervical cancer (stage IA2-IIA) with at least one risk factor for recurrence. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. Meta-analysis was performed using a random-effects model, with death and disease progression as outcomes. MAIN RESULTS: For this updated version, we identified three additional ongoing trials but no new studies for inclusion. Three trials including 368 evaluable women with early cervical cancer were included in the meta-analyses. The median follow-up period in these trials ranged from 29 to 42 months. All women had undergone surgery first. Two trials compared chemotherapy combined with radiotherapy to radiotherapy alone; and one trial compared chemotherapy followed by radiotherapy to radiotherapy alone. It was not possible to perform subgroup analyses by stage or tumour size.Compared with adjuvant radiotherapy, chemotherapy combined with radiotherapy significantly reduced the risk of death (two trials, 297 women; hazard ratio (HR) = 0.56, 95% confidence interval (CI): 0.36 to 0.87) and disease progression (two trials, 297 women; HR = 0.47, 95% CI 0.30 to 0.74), with no heterogeneity between trials (I² = 0% for both meta-analyses). Acute grade 4 toxicity occurred significantly more frequently in the chemotherapy plus radiotherapy group than in the radiotherapy group (risk ratio (RR) 5.66, 95% CI 2.14 to 14.98). We considered this evidence to be of a moderate quality due to small numbers and limited follow-up in the included studies. In addition, it was not possible to separate data for bulky early stage disease.In the one small trial that compared adjuvant chemotherapy followed by radiotherapy with adjuvant radiotherapy alone there was no significant difference in disease recurrence between the groups (HR = 1.34; 95% CI 0.24 to 7.66) and OS was not reported. We considered this evidence to be of a low quality.No trials compared adjuvant platinum-based chemotherapy with no adjuvant chemotherapy after surgery for early cervical cancer with risk factors for recurrence. AUTHORS' CONCLUSIONS: The addition of platinum-based chemotherapy to adjuvant radiotherapy (chemoradiation) may improve survival in women with early stage cervical cancer (IA2-IIA) and risk factors for recurrence. Adjuvant chemoradiation is associated with an increased risk of severe acute toxicity, although it is not clear whether this toxicity is significant in the long-term due to a lack of long-term data. This evidence is limited by the small numbers and poor methodological quality of included studies. We await the results of three ongoing trials, that are likely to have an important impact on our confidence in this evidence.

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BACKGROUND: Breast cancer (BC) is a major public health problem, with rising incidence in many regions of the globe. Although mortality has recently dropped in developed countries, death rates are still increasing in some developing countries, as seen in Brazil. Among the reasons for this phenomenon are the lack of structured screening programs, a long waiting period between diagnosis and treatment, and lack of access to health services for a large proportion of the Brazilian population. METHODS AND DESIGN: Since 2004, an intervention study in a cohort of women in Southern Brazil, denominated Porto Alegre Breast Health Intervention Cohort, is being conducted in order to test the effectiveness and cost-effectiveness of a model for BC early detection and treatment. In this study, over 4,000 women from underserved communities aged 40 to 69 years are being screened annually with mammography and clinical breast examination performed by a multidisciplinary team, which also involves nutritional counseling and genetic cancer risk assessment. Risk factors for BC development are also being evaluated. Active search of participants by lay community health workers is one of the major features of our program. The accrual of new participants was concluded in 2006 and the study will last for 10 years. The main goal of the study is to demonstrate significant downstaging of BC in an underserved population through proper screening, attaining a higher rate of early-stage BC diagnoses than usually seen in women diagnosed in the Brazilian Public Health System. Preliminary results show a very high BC incidence in this population (117 cases per 100,000 women per year), despite a low prevalence of classical risk factors. DISCUSSION: This study will allow us to test a model of BC early diagnosis and treatment and evaluate its cost-effectiveness in a developing country where the mortality associated with this disease is very high. Also, it might contribute to the evaluation of risk factors in a population with a different ethnic background from that studied in developed countries. If our model is proven effective, it may be replicated in other parts of the globe where BC is also a major public health problem.

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The 30-year experience in improving detection of breast cancer in the Breast Unit of the Hospital de Clínicas, Federal University of Rio Grande do Sul, Brazil (1972-2002) is reported. We retrospectively analyzed the behavior of surrogate parameters of early breast cancer detection, such as the mean tumor diameter at diagnosis, clinical staging, as well as the percentage of breast conservative surgery along this period of three decades. From 2,103 identified women, 1,607 women met our criteria for study entry and had follow-up information, constituting our study cohort. Statistical tests were two-sided and considered significant at p < 0.05. There was a decrease of about 0.8 cm in the median tumor diameter over this 30-year period. The incidence of early-stage tumors increased progressively over time, and the percentage of patients presenting with stage I breast cancer doubled in 30 years. The Halsted procedure that represented 11.5% of surgeries in the 1970s is a very rare procedure nowadays (<1% of cases). Modified radical mastectomy was the procedure applied in about 50% of women with invasive breast cancer during these 30 years of observation. Notably, breast conservative surgery increased from 17.3% in the 1970s to 43.2% in the 2000s, while the decrease in tumor size and clinical staging was accompanied by an increased number of breast conservative surgical procedures. In geographic areas where coordinated preventive efforts are not thoroughly available, analysis of subsets of the patient population using tumor size as a surrogate represents an indirect way to observe long-term effects of prevention. The present study shows that tumor size is a surrogate for populations from developing countries too and gives scientific support for the design of continuous comprehensive programs of breast cancer prevention in this setting.

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On the basis of the demonstrated single-agent activity of cisplatin in patients with advanced cervical cancer and the observation of in vitro synergism between this agent and decitabine, a new DNA hypomethylating agent, we designed a phase II trial in which the combined use of the two agents are used as first-line therapy in patients with recurrent and/or metastatic disease. Eligible patients were those with histopathologically proven diagnosis of squamous cell carcinoma of the cervix, which was not considered suitable for curative surgery and/or irradiation, having measurable disease, leukocyte counts more than or equal to 4,000/microl, thrombocyte counts more than or equal to 100,000/microl, serum creatinine more than or equal to 1.5 mg/dl, and normal liver function tests. Initial dose of cisplatin was 40 mg/m(2), whereas decitabine was 50 mg/m(2) for 3 consecutive days every 21 days. Because of toxicity, the dose of cisplatin was reduced to 30 mg/m(2). Twenty-five patients were included in the study; 24 of them were eligible for the evaluation of toxicity, whereas 21 of them were eligible for the evaluation of tumor responses. Nineteen (79.2%) patients had received prior radiotherapy. A total of 75 cycles of chemotherapy were administered to the patients, with a median of 3 cycles (range: 1-8) per patient. The most frequently observed side effect was neutropenia, which was National Cancer Institute- Common Toxicity Criteria grades III and IV in 68.0% of cases. One patient died of complications caused by drug-related neutropenic sepsis. The most common nonhematologic grades III and IV toxicities were nausea and vomiting, which occurred in 17.3% and 9.3% of the cycles, respectively. Of a total of 21 patients evaluable for tumor response, 8 (38.1%) achieved a partial response, whereas stable disease was documented in 5 cases (23.8%). Median progression-free interval (PFI) was 16 weeks, and median survival was 19 weeks (95% CI 7.9-31.2). Objective responses were more frequent in patients with metastatic lesions in nonirradiated sites. Cisplatin- decitabine combination was moderately active in patients with advanced squamous cell carcinoma of the cervix, mainly in patients presenting with metastatic disease at previously nonirradiated sites. However, this regimen produced significant hematologic toxicity. Further studies with this combination including a larger patient population, preferably with the concomitant administration of hematopoietic growth factors, are warranted.

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É relatado um caso de angiossarcoma primário de baço em um homem de 29 anos, fazendo-se a revisäo dos achados clínicos, diagnóstico anatomopatológico, tratamento e prognóstico. Angiossarcomas correspondem a menos de 1 porcento dos sarcomas de tecidos moles, e somente uma pequena fraçäo surge no baço. Esses tumores freqüentemente apresentam-se como um desafio diagnóstico para o patologista, tendo em vista as variaçöes na histologia, e o desenvolvimento de novos marcadores em painéis de imuno histoquímica, como o CD31, ajudam a descartar outros diagnósticos. Devido à raridade desse tumor näo existe um consenso em relaçäo ao tratamento quimioterápico e, via de regra, o prognóstico é ruim.

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Este estudo foi realizado em 1988 para avaliar a prevalência de fumantes, o grau de conscientizaçäo de fumantes e ex-fumantes e o papel dos profissionais da saúde no combate ao tabagismo em Porto Alegre. Após amostragem, foram entrevistadas 407 pessoas de 15 a 64 anos. Destas, 170 (41,8%) fumavam. Entre ex-fumantes, 85,7% pararam de fumar por estarem conscientes da toxicidade do cigarro. Apenas 16,9% dos fumante e ex-fumantes foram alertados sobre os malefícios do cigarro por profissionais da saúde antes de terem começado a fumar. Após terem começado, somente 51,5% deles foram alertados. Estes índices säo alarmantes, pois acreditamos ser a prevençäo a melhor forma de combater ao tabagismo

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