Time interval between diagnosis to treatment of breast cancer and the impact of health insurance coverage: a sub analysis of the AMAZONA III Study (GBECAM 0115).

PURPOSE: Breast cancer (BC) is the most common type of cancer among women in Brazil. Evidence shows that delayed treatment onset is associated with increased mortality. This study aimed to evaluate median days between diagnosis and treatment and factors associated with delayed start of treatment (> 60 days after diagnosis): stage, treatment received, subtype, epidemiological characteristics, and type of healthcare coverage. METHODS: This analysis included 1709 stage I-III BC patients from AMAZONA III, a prospective, observational study, diagnosed from January 2016 to March 2018 in 22 centers in Brazil. RESULTS: The median number of days from diagnosis to beginning of first oncologic treatment was 46 days (IQR 28-75) overall, 43 days (IQR 25-75) for stage I disease, 49 days (IQR 28-81) for stage II, and 44 days (IQR 30-68) for stage III, (p = 0.1180). According to first treatment received, diagnosis-to-treatment interval was 43 days (IQR 29-65) for neoadjuvant chemotherapy and 48 days (IQR 26-81) for surgery. Diagnosis-to-treatment interval was higher in women treated in the public system versus the private system (56 vs. 34 days, p < 0.0001). Patients in the public system had an increased odds of delayed treatment initiation (OR 4.74 95% CI 3.09-7.26, p < .0001). The longer interval from diagnosis to treatment in the public system was independent of clinical stage, type of treatment (systemic vs surgery first), subtype and region of the country. CONCLUSION: By characterizing the delays in care delivery, our study will aid stakeholders to better design interventions and allocate resource to improve timely treatment for breast cancer in Brazil. CLINICALTRIALS: gov Identifier: NCT02663973, registered on January, 26th, 2016.

Biomarker Analysis of the Phase III NALA Study of Neratinib + Capecitabine versus Lapatinib + Capecitabine in Patients with Previously Treated Metastatic Breast Cancer.

PURPOSE: Neratinib plus capecitabine (N+C) demonstrated significant progression-free survival (PFS) benefit in NALA (NCT01808573), a randomized phase III trial comparing N+C with lapatinib + capecitabine (L+C) in 621 patients with HER2-positive (HER2+) metastatic breast cancer (MBC) who had received ≥2 prior HER2-directed regimens in the metastatic setting. We evaluated correlations between exploratory biomarkers and PFS. PATIENTS AND METHODS: Somatic mutations were evaluated by next-generation sequencing on primary or metastatic samples. HER2 protein expression was evaluated by central IHC, H-score, and VeraTag/HERmark. p95 expression (truncated HER2) was measured by VeraTag. HRs were estimated using unstratified Cox proportional hazards models. RESULTS: Four hundred and twenty samples had successful sequencing: 34.0% had PIK3CA mutations and 5.5% had HER2 (ERBB2) mutations. In the combined patient populations, PIK3CA mutations trended toward shorter PFS [wild-type vs. mutant, HR = 0.81; 95% confidence interval (CI), 0.64-1.03], whereas HER2 mutations trended toward longer PFS [HR = 1.69 (95% CI, 0.97-3.29)]. Higher HER2 protein expression was associated with longer PFS [IHC 3+ vs. 2+, HR = 0.67 (0.54-0.82); H-score ≥240 versus <240, HR = 0.77 (0.63-0.93); HERmark positive vs. negative, HR = 0.76 (0.59-0.98)]. Patients whose tumors had higher HER2 protein expression (any method) derived an increased benefit from N+C compared with L+C [IHC 3+, HR = 0.64 (0.51-0.81); H-score ≥ 240, HR = 0.54 (0.41-0.72); HERmark positive, HR = 0.65 (0.50-0.84)], as did patients with high p95 [p95 ≥2.8 relative fluorescence (RF)/mm2, HR = 0.66 (0.50-0.86) vs. p95 < 2.8 RF/mm2, HR = 0.91 (0.61-1.36)]. CONCLUSIONS: PIK3CA mutations were associated with shorter PFS whereas higher HER2 expression was associated with longer PFS. Higher HER2 protein expression was also associated with a greater benefit for N+C compared with L+C.

The impact of sociodemographic factors and health insurance coverage in the diagnosis and clinicopathological characteristics of breast cancer in Brazil: AMAZONA III study (GBECAM 0115).

PURPOSE: In Brazil, the available cancer registries are deficient in number and quality and, hence, little information is known regarding sociodemographic, clinicopathological characteristics, treatment patterns, and outcomes of breast cancer (BC) patients. We performed the AMAZONA III/ GBECAM 0115 study and in this analysis, we describe patients' characteristics at diagnosis and their association with health insurance type. METHODS: This is a prospective cohort study developed in 23 sites in Brazil including women with newly diagnosed invasive BC from January 2016 to March 2018. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured. RESULTS: A total of 2950 patients were included in the study. Median age at diagnosis was 53.9 years; 63.1% were publicly insured. The majority of patients (68.6%) had stage II-III breast cancer and ductal carcinoma histology (80.9%). The most common breast cancer subtype was luminal A-like (48.0%) followed by luminal B-HER2 positive-like (17.0%) and triple-negative (15.6%). Luminal A was more frequent in private (53.7% vs. 44.2%, p < .0001) than public, whereas Luminal B HER2-positive (19.2% vs. 14.2%, p = 0.0012) and HER2-positive (8.8% vs. 5.1%, p = 0.0009) were more common in patients with public health system coverage. Only 34% of patients were diagnosed by screening exams. Privately insured patients were more frequently diagnosed with stage I disease when compared to publicly insured patients; publicly insured patients had more stage III (33.5% vs. 14.7%; p-value < 0.0001) disease than privately insured ones. Breast cancer was detected by symptoms more frequently in publicly than in privately insured patients (74.2% vs 25.8%, respectively; p-value < 0.0001). CONCLUSIONS: Patients with public health coverage were diagnosed with symptomatic disease, later stages and more aggressive subtypes when compared to privately insured patients.

Advanced Stage at Diagnosis and Worse Clinicopathologic Features in Young Women with Breast Cancer in Brazil: A Subanalysis of the AMAZONA III Study (GBECAM 0115).

PURPOSE: Breast cancer (BC) in young women is uncommon and tends to present with more aggressive characteristics. To better understand and characterize this scenario in Brazil through real-world data, we performed a subanalysis of AMAZONA III study (ClinicalTrials.gov identifier: NCT02663973). METHODS: The AMAZONA III study (GBECAM 0115) is a prospective registry that included 2,950 women newly diagnosed with invasive BC in Brazil from January 2016 until March 2018 at 22 sites. Valid data were obtained from 2,888 patients regarding age at diagnosis and complete baseline information. To compare epidemiologic and clinicopathological features at the time of diagnosis, patients with BC were divided into two groups according to age: ≤ 40 years and > 40 years. Quantitative variables were described as means, and categorical variables were described as frequencies and percentages and compared using the Pearson's χ2 test. RESULTS: Of 2,888 women diagnosed with BC, 486 (17%) were ≤ 40 years old. Young women had higher educational level, most were employed and a significant number were married (P < .001 for all associations). Younger patients were more symptomatic at BC diagnosis (P < .001), and they also presented more frequently with stage III, T3/T4, grade 3 tumors, HER-2-positive, luminal B, and triple-negative subtypes. CONCLUSION: Brazilian women younger than age 40 years have unfavorable clinicopathological features of BC at diagnosis, with more aggressive subtypes and advanced stage when compared with older women. These differences are not explained by socioeconomic or ethnic imbalances. The causes of a higher prevalence of BC among young women in Brazil deserve additional investigation.

Characteristics and prognosis of stage I-III breast cancer subtypes in Brazil: The AMAZONA retrospective cohort study.

OBJECTIVE: To describe stage I-III breast cancer (BC) molecular subtypes and outcomes among a cohort of patients from Brazil. METHODS: AMAZONA study is a retrospective cohort conducted from June 2008 to January 2009 including women of at least 18 years old, with histologically proven breast cancer, diagnosed in 2001 (n = 2198) and 2006 (n = 2714). In this analysis, we included patients who underwent surgery, had stage I-III disease and available pathological information (n = 2296). We estimated molecular subtypes by local immunohistochemical stains. Data was obtained from medical charts and public databases. RESULTS: Mean age at diagnosis was 54 years and 41.1% were younger than 50 years. 23.3% were diagnosed in stage I, 53.5% in stage II and 23.2% in stage III. 80.8% were treated in the public health system. 71.3% had hormonal receptor positive disease, 15.7% were HER-2 positive and 21.1% had triple-negative breast cancer. 55.6% were treated with mastectomy and 96.2% received adjuvant treatment (82.2% chemotherapy). 13.4% of HER-2 positive patients received adjuvant trastuzumab. Overall survival rate at 5 years was 96.84% for stage I, 94.16% for stage II and 70.48% for stage III. Molecular subtypes were independent prognostic factor in stages II and III patients. CONCLUSIONS: Brazilian women have a higher risk of being diagnosed with late stage breast cancer and younger age than in high-income countries. Luminal-like disease is the most common molecular subtype in the country. Triple negative and HER-2 positive had the worst prognosis.

Complete axillary dissection without drainage for the surgical treatment of breast cancer: a randomized clinical trial.

OBJECTIVE:: This randomized clinical trial evaluated the possibility of not draining the axilla following axillary dissection. METHODS:: The study included 240 breast cancer patients who underwent axillary dissection as part of conservative treatment. The patients were divided into two groups depending on whether or not they were subjected to axillary drainage. ClinicalTrials.gov: NCT01267552. RESULTS:: The median volume of fluid aspirated was significantly lower in the axillary drainage group (0.00 ml; 0.00 - 270.00) compared to the no drain group (522.50 ml; 130.00 - 1148.75). The median number of aspirations performed during conservative breast cancer treatment was significantly lower in the drainage group (0.5; 0.0 - 4.0) compared to the no drain group (5.0; 3.0 - 7.0). The total volume of serous fluid produced (the volume of fluid obtained from drainage added to the volume of aspirated fluid) was similar in the two groups. Regarding complications, two cases (2.4%) of wound dehiscence occurred in the drainage group compared to 13 cases (13.5%) in the group in which drainage was not performed, with this difference being statistically significant. Rates of infection, necrosis and hematoma were similar in both groups. CONCLUSION:: Safety rates were similar in both study groups; hence, axillary dissection can feasibly be performed without drainage. However, more needle aspirations could be required, and there could be more cases of wound dehiscence in patients who do not undergo auxiliary drainage.

Complete axillary dissection without drainage for the surgical treatment of breast cancer: a randomized clinical trial

OBJECTIVE: This randomized clinical trial evaluated the possibility of not draining the axilla following axillary dissection. METHODS: The study included 240 breast cancer patients who underwent axillary dissection as part of conservative treatment. The patients were divided into two groups depending on whether or not they were subjected to axillary drainage. ClinicalTrials.gov: NCT01267552. RESULTS: The median volume of fluid aspirated was significantly lower in the axillary drainage group (0.00 ml; 0.00 - 270.00) compared to the no drain group (522.50 ml; 130.00 - 1148.75). The median number of aspirations performed during conservative breast cancer treatment was significantly lower in the drainage group (0.5; 0.0 - 4.0) compared to the no drain group (5.0; 3.0 - 7.0). The total volume of serous fluid produced (the volume of fluid obtained from drainage added to the volume of aspirated fluid) was similar in the two groups. Regarding complications, two cases (2.4%) of wound dehiscence occurred in the drainage group compared to 13 cases (13.5%) in the group in which drainage was not performed, with this difference being statistically significant. Rates of infection, necrosis and hematoma were similar in both groups. CONCLUSION: Safety rates were similar in both study groups; hence, axillary dissection can feasibly be performed without drainage. However, more needle aspirations could be required, and there could be more cases of wound dehiscence in patients who do not undergo auxiliary drainage.

Resposta prolongada durante 43 ciclos de trastuzumabe entansina (T?DM1) em paciente com câncer de mama metastático com superexpressão de HER2: relato de caso / Prolonged response for 43 cycles of trastuzumab entansine (T?DM1) in apatient with metastatic breast cancer with HER2 overexpression: case report

O objetivo deste trabalho foi relatar o caso de uma paciente portadora de câncer de mama metas tático com superexpressão de HER2 que fez uso de trastuzumabe entansina (T DM1), enquanto randomizada em um estudo clínico de fase III e que apresentou resposta completa e duradora das lesões alvo. As informações foram obtidas por meio de revisão do prontuário, entrevista com a pa ciente e revisão de questionários aos quais a paciente foi submetida. Este relato de caso se justifica devido à longa duração de resposta clínica e à segurança de T DM1 como nova droga antiHER.

O objetivo deste trabalho foi relatar o caso de uma paciente portadora de câncer de mama metas tático com superexpressão de HER2 que fez uso de trastuzumabe entansina (T DM1), enquanto randomizada em um estudo clínico de fase III e que apresentou resposta completa e duradora das lesões alvo. As informações foram obtidas por meio de revisão do prontuário, entrevista com a pa ciente e revisão de questionários aos quais a paciente foi submetida. Este relato de caso se justifica devido à longa duração de resposta clínica e à segurança de T DM1 como nova droga antiHER.

Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas.

BACKGROUND: Deregulation of cellular energetic metabolism was recently pointed out as a hallmark of cancer cells. This deregulation involves a metabolic reprogramming that leads to a high production of lactate. Lactate efflux, besides contributing for the glycolytic flux, also acts in the extracellular matrix, contributing for cancer malignancy, by, among other effects, induction of angiogenesis. However, studies on the interplay between cancer metabolism and angiogenesis are scarce. Therefore, the aim of the present study was to evaluate the metabolic and vascular molecular profiles of cervical adenocarcinomas, their co-expression, and their relation to the clinical and pathological behavior. METHODS: The immunohistochemical expression of metabolism-related proteins (MCT1, MCT4, CD147, GLUT1 and CAIX) as well as VEGF family members (VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2 and VEGFR-3) was assessed in a series of 232 cervical adenocarcinomas. The co-expression among proteins was assessed and the expression profiles were associated with patients' clinicopathological parameters. RESULTS: Among the metabolism-related proteins, MCT4 and CAIX were the most frequently expressed in cervical adenocarcinomas while CD147 was the less frequently expressed protein. Overall, VEGF family members showed a strong and extended expression with VEGF-C and VEGFR-2 as the most frequently expressed and VEGFR-1 as the less expressed member. Co-expression of MCT isoforms with VEGF family members was demonstrated. Finally, MCT4 was associated with parametrial invasion and HPV18 infection, CD147 and GLUT1 with distant metastasis, CAIX with tumor size and HPV18 infection, and VEGFR-1 with local and lymphnode metastasis. CONCLUSIONS: The results herein presented provide additional evidence for a crosstalk between deregulating cellular energetics and inducing angiogenesis. Also, the metabolic remodeling and angiogenic switch are relevant to cancer progression and aggressiveness in adenocarcinomas.

Incidence trend for breast cancer among young women in Goiânia, Brazil.

CONTEXT AND OBJECTIVE: It has been suggested that there has been a large increase in breast cancer incidence among young women over the last decade. The aim of this study was to describe the incidence of breast cancer among young women up to 39 years of age in Goiânia, between 1988 and 2003, and to compare this with other age groups. DESIGN AND SETTING: Retrospective study using the database of the Population-based Cancer Registry of Goiânia, State of Goiás, Brazil. METHODS: The incidence was calculated according to age groups: up to 39 years, 40 to 59 years and 60 years and over. Average annual percentage changes (AAPCs) were estimated for the different age groups using Poisson regression. RESULTS: Over this period, 3,310 new cases were recorded. The standardized incidence was 2.89/100,000 in 1988 and increased to 6.37/100,000 in 2003 (R(2) = 0.52) for the group aged up to 39 years (p < 0.003). For the group from 40 to 59 years old, the incidence was 14.39/100,000 in 1988 and 41.70/100,000 in 2003 (R(2) = 0.85; p < 0.001). For the group aged 60 years and over, it was 17.62/100,000 and 28.49/100,000, respectively (R(2) = 0.67; p < 0.001). The AAPCs were 5.22%, 5.53% and 4.54% for the age groups up to 39, 40 to 59 and 60 years and over, respectively. CONCLUSIONS: The incidence of breast cancer among young women in Goiânia has been increasing significantly, although this change was similar to the increase in other age groups.

Incidence trend for breast cancer among young women in Goiânia, Brazil / Tendência de incidência de câncer de mama entre mulheres jovens em Goiânia, Brasil

CONTEXT AND OBJECTIVE: It has been suggested that there has been a large increase in breast cancer incidence among young women over the last decade. The aim of this study was to describe the incidence of breast cancer among young women up to 39 years of age in Goiânia, between 1988 and 2003, and to compare this with other age groups. DESIGN AND SETTING: Retrospective study using the database of the Population-based Cancer Registry of Goiânia, State of Goiás, Brazil. METHODS: The incidence was calculated according to age groups: up to 39 years, 40 to 59 years and 60 years and over. Average annual percentage changes (AAPCs) were estimated for the different age groups using Poisson regression. RESULTS: Over this period, 3,310 new cases were recorded. The standardized incidence was 2.89/100,000 in 1988 and increased to 6.37/100,000 in 2003 (R² = 0.52) for the group aged up to 39 years (p < 0.003). For the group from 40 to 59 years old, the incidence was 14.39/100,000 in 1988 and 41.70/100,000 in 2003 (R² = 0.85; p < 0.001). For the group aged 60 years and over, it was 17.62/100,000 and 28.49/100,000, respectively (R² = 0.67; p < 0.001). The AAPCs were 5.22 percent, 5.53 percent and 4.54 percent for the age groups up to 39, 40 to 59 and 60 years and over, respectively. CONCLUSIONS: The incidence of breast cancer among young women in Goiânia has been increasing significantly, although this change was similar to the increase in other age groups.

CONTEXTO E OBJETIVO: Tem sido sugerido que há um grande aumento na incidência do câncer de mama em mulheres jovens na última década. O objetivo deste estudo é descrever a incidência do câncer de mama em mulheres jovens (até 39 anos) em Goiânia, entre 1988 e 2003, comparando com os demais grupos etários. DESENHO E LOCAL: Estudo retrospectivo utilizando o banco de dados do Registro de Câncer de Base populacional de Goiânia/Goiás, Brasil. MÉTODOS: As incidências foram calculadas de acordo com os grupos etários: até 39 anos, 40 a 59 anos e, 60 anos acima. A mudança da média percentual anual (MMPA) foi estimada para os diferentes grupos usando a regressão de Poisson. RESULTADOS: No período, foram registrados 3.310 novos casos. A incidência padronizada foi de 2,89/100.000 em 1988 tendo aumentado para 6,37/100.000 em 2003 (R² = 0,52) para o grupo com até 39 anos (p < 0,003). Para o grupo de 40 a 59 anos a incidência foi de 14,39/100.000 em 1988 e de 41,70/100.000 em 2003 (R² = 0,85; p < 0,001); para o grupo de 60 anos e acima foi de 17,62/100.000 e 28,49/100.000, respectivamente (R² = 0,67; p < 0,001). A MMPA foi de 5,22 por cento, 5,53 por cento e 4,54 por cento para os grupos etários de até 39 anos, 40 a 59 e 60 ou mais, respectivamente. CONCLUSÕES: A incidência de câncer de mama em mulheres jovens em Goiânia vem aumentando significativamente, entretanto esse aumento é semelhante ao observado nos demais grupos etários.

Prevalence of paresthesia, fatigue, edema and pain after treatment for breast cancer

Objective: To investigate the prevalence of chronic symptoms among patients who underwent breast cancer treatment, and to determine the factors that might be related to these symptoms. Material and Methods: A questionnaire was applied to 87 patients undergoing breast cancer follow-up. It evaluated the length of time since treatment, therapeutic procedure (type of surgery, chemotherapy, radiotherapy and/or endocrine therapy), use of analgesic medication, location and intensity of pain and presence of paresthesia, fatigue and upper-limb edema. Results: The patients’ mean age was 54.46 years; the mean interval between locoregional treatment and the interview was 52.95 months. The prevalence of paresthesia symptoms was 65.5 percent; fatigue, 49.4 percent; edema, 31 percent; and pain, 31 percent. From multivariate analysis, we observed that fatigue was influenced by mastectomy (OR = 2.680; 95 percent CI = 1.127 - 6.373), radiotherapy (OR = 3.028; 95 percent CI = 1.142 - 8.030) and chemotherapy (OR = 5.271; 95 percent CI = 1.067 - 26.034), and was lower among patients who underwent endocrine therapy (OR = 0.407; 95 percent CI = 0.171 - 0.967). Paresthesia, edema and pain were not influenced by any of the therapeutic types. Conclusions: There was high prevalence of complaints among the patients who had undergone breast cancer treatment. Fatigue was the only symptom influenced by the different treatments.

Monocarboxylate transporters 1 and 4 are associated with CD147 in cervical carcinoma.

Due to the highly glycolytic metabolism of solid tumours, there is an increased acid production, however, cells are able to maintain physiological pH through plasma membrane efflux of the accumulating protons. Acid efflux through MCTs (monocarboxylate transporters) constitutes one of the most important mechanisms involved in tumour intracellular pH maintenance. Still, the molecular mechanisms underlying the regulation of these proteins are not fully understood. We aimed to evaluate the association between CD147 (MCT1 and MCT4 chaperone) and MCT expression in cervical cancer lesions and the clinico-pathological significance of CD147 expression, alone and in combination with MCTs. The series included 83 biopsy samples of precursor lesions and surgical specimens of 126 invasive carcinomas. Analysis of CD147 expression was performed by immunohistochemistry. CD147 expression was higher in squamous and adenocarcinoma tissues than in the non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more frequently expressed in CD147 positive cases. Additionally, co-expression of CD147 with MCT1 was associated with lymph-node and/or distant metastases in adenocarcinomas. Our results show a close association between CD147 and MCT1 and MCT4 expressions in human cervical cancer and provided evidence for a prognostic value of CD147 and MCT1 co-expression.

Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma.

BACKGROUND: Adenosquamous carcinoma of the uterine cervix is an infrequent but aggressive subtype of cervical cancer. A better understanding of its biological behaviour is warranted to define more accurate prognosis and therapeutic targets. Currently, the blockage of receptor tyrosine kinase (RTKs) activity is an efficient therapeutic strategy for many different cancers. The objective of this study was to investigate EGFR, PDGFRA and VEGFR2 RTKs overexpression and activating gene mutations in a cohort of 30 adenosquamous carcinomas of the uterine cervix. METHODS: EGFR, PDGFRA and VEGFR2 immunohistochemistry was performed in all samples, followed by DNA isolation from the gross macroscopically dissection of the neoplastic area. Screening for EGFR (exons 18-21) and PDGFRA (exons 12, 14 and 18) mutations was done by PCR--single-strand conformational polymorphism (PCR-SSCP). RESULTS: Despite the presence of EGFR immunohistochemical positive reactions in 43% (13/30) of the samples, no EGFR activating mutations in the hotspot region (exons 18-21) were identified. A silent base substitution (CAG>CAA) in EGFR exon 20 at codon 787 (Q787Q) was found in 17 cases (56%). All PDGFRA immunohistochemical reactions were positive and consistently observed in the stromal component, staining fibroblasts and endothelial cells, as well as in the cytoplasm of malignant cells. No activating PDGFRA mutations were found, yet, several silent mutations were observed, such as a base substitution in exon 12 (CCA>CCG) at codon 567 (P567P) in 9 cases and in exon 18 (GTC>GTT) at codon 824 (V824V) in 4 cases. We also observed the presence of base substitutions in intron 14 (IVS14+3G>A and IVS14+49G>A) in two different cases, and in intron 18 (IVS18-50insA) in 4 cases. VEGFR2 positivity was observed in 22 of 30 cases (73.3%), and was significantly associated with lack of metastasis (p=0.038). CONCLUSION: This is the most extensive analysis of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinomas. Despite the absence of EGFR and PDGFRA activating mutations, the presence of overexpression of these three important therapeutic targets in a subset of cases may be important in predicting the sensitivity of adenosquamous carcinoma to specific anti-RTKs drugs.

Increasing expression of monocarboxylate transporters 1 and 4 along progression to invasive cervical carcinoma.

Solid tumor cells are known to be highly glycolytic and, to prevent apoptosis by cellular acidosis, cells increase proton efflux through pH regulators, such as monocarboxylate transporters (MCTs). However, the role of these membrane proteins in solid tumor development and survival is not fully understood. We aimed to evaluate the expression of the MCT isoforms 1, 2, and 4 in a large series of cervical lesions (neoplastic and non-neoplastic) and assess its clinical-pathologic significance. The series analyzed included 29 chronic cervicitis, 30 low-grade squamous intraepithelial lesions, 32 high-grade squamous intraepithelial lesions, 49 squamous cell carcinomas, 51 adenocarcinomas, and 30 adenosquamous carcinomas of the uterine cervix. Analysis of the expression of MCT isoforms 1, 2, and 4 was performed by immunohistochemistry with specific antibodies. Immunoreactions were evaluated both qualitatively and semiquantitatively. We found a significant increase in MCT expression from preinvasive to invasive squamous lesions and from normal glandular epithelium to adenocarcinomas. This is the first study evaluating the significance of MCT expression in lesions of the uterine cervix, including invasive carcinomas, and the results found herein led us to believe that these membrane proteins are involved in the progression to invasiveness in uterine cervix carcinoma.

KIT activation in uterine cervix adenosquamous carcinomas by KIT/SCF autocrine/paracrine stimulation loops.

OBJECTIVES: Uterine adenosquamous carcinoma (ASC) is an uncommon, yet, one of the most aggressive cervical cancer subtype. The successful treatment of some tumors, such as gastrointestinal stromal tumors (GISTs), by anti-KIT inhibitors fosters the study of this receptor tyrosine kinase in other malignancies. In the present study, we intended to molecularly characterize KIT in ASC. METHODS: In a series of 30 cases, we studied KIT (CD117), KIT phosphorylated/activated form, as well as KIT ligand, stem cell factor (SCF), by immunohistochemistry. We further screened for KIT hotspot mutations (exon 9, 11, 13 and 17) by PCR-SSCP and for KIT gene amplification by Quantitative real-time PCR in CD117 positive cases. RESULTS: We observed CD117 expression in approximately 13% of cases, with approximately 7% co-expressing SCF, which resulted in KIT phosphorylation/activation. No KIT activating mutations or gene amplification were found, despite the presence of 4q aneuploidy in one case. CONCLUSIONS: This is the first study assessing KIT activation and molecular alterations in a large series of rare ASC. Our findings showed the absence of KIT molecular alterations and suggested the presence of KIT activation in a small proportion of cases through KIT/SCF co-expression.

Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix.

OBJECTIVE: We sought to determine the significance of lymphatic vessel density (LVD) in pre-malignant lesions and carcinomas of the uterine cervix and to evaluate the prognostic value of lymphatic invasion and D2-40 positivity in tumor cells in the three histological types of invasive lesions. The correlation of LVD, lymphatic invasion and D2-40 positivity in tumor cells with EGFR and COX-2 expressions was also evaluated. METHODS: We studied 50 cervicitis, 50 low-grade squamous intraepithelial lesions (LSIL) (CIN1), 51 high-grade squamous intraepithelial lesions (HSIL) (CIN2/CIN3), 49 invasive squamous cells carcinomas (SCC), 43 adenocarcinomas (AC) and 30 adenosquamous cells carcinomas (ASC). The immunoreaction assay was performed using the monoclonal antibody D2-40. RESULTS: Significant differences in LVD were found among all categories of pre-invasive and invasive lesions (p=0.001 and p<0.001, respectively). LVD in invasive lesions was significantly greater than in pre-invasive lesions (p<0.001) and no significant association was found between LVD in invasive lesions and both lymph node invasion and/or metastasis. D2-40 positivity in tumor cells was associated with a better prognosis in ASC cases. EGFR and COX-2 expressions in invasive lesions were not associated with LVD; however, they correlated with both lymphatic invasion and D2-40 positivity in tumor cells. CONCLUSIONS: Lymphatic neovascularization begins early in intraepithelial lesions and continues to increase towards malignancy. Both lymphatic invasion and decrease in D2-40 expression in tumor cells appear to have a prognostic value.

Cyclooxygenase-2 and epidermal growth factor receptor expressions in different histological subtypes of cervical carcinomas.

This study was designed to evaluate the significance of cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) expression in a series of cervical adenocarcinoma (AC), cervical adenosquamous carcinoma (ASC), and cervical squamous cell carcinoma (SCC). One hundred thirty cases of cervical carcinoma (30 ASC, 50 AC, and 50 SCC) were analyzed for COX-2 and EGFR expressions using specific primary antibodies. Samples were scored semiquantitatively as follows: (-), 0% of immunoreactive cells; (+), <5% of immunoreactive cells; (++), 5% to 50% of immunoreactive cells; and (+++), >50% of immunoreactive cells. The COX-2 expression was more frequently positive than EGFR in all cervical cancers studied. The COX-2 expression was also more prominent in AC than in ASC (P = 0.003). Expression of either COX-2 or EGFR was significantly different when comparing SCC with AC (P < 0.001 and P = 0.04, respectively). There was no significant correlation between COX-2 and EGFR expressions and age at diagnosis, recurrence, distant metastasis, and/or positive status of regional lymph nodes, neither between COX-2 and EGFR coexpression and the clinical data analyzed. Nevertheless, our data support that there are significant differences between EGFR and COX-2 expressions in the 3 different histogenetic types of cervical cancer. Also, in terms of therapeutic strategies, our data can be valuable in the selection of patients eligible to receive specific EGFR/COX-2-targeted therapy.

Modified radical mastectomy sparing one or both pectoral muscles in the treatment of breast cancer: intra and postoperative complications.

CONTEXT AND OBJECTIVE: Modified radical mastectomy is widely utilized in breast cancer treatment. However, no prospective comparison has yet been made between the Madden technique (preservation of the pectoralis minor muscle) and the Patey technique (resection of this muscle). The aim of this work was to compare these two modified radical mastectomy techniques, by analyzing their degrees of difficulty and complications. DESIGN AND SETTING: Randomized trial at the Breast Unit of Hospital Araújo Jorge, Goiás; and Faculdade de Medicina da Universidade Federal de Goiás. METHODS: 430 patients with breast cancer with an indication for modified radical mastectomy were included in the program, of whom 426 patients were available for analysis (225 allocated to Patey and 201 to Madden). The chi-squared and Student t tests were used for analysis. RESULTS: The patients demographics were well balanced between the two groups. The mean duration of the surgical procedures was 105 (+/- 29.9) and 102 minutes (+/- 33), for the Patey and Madden groups, respectively (p = 0.6). Hospitalization duration was 2.3 days for both groups. The mean number of lymph nodes resected was 20.3 (+/- 7.6) for Patey and 19.8 (+/- 8.1) for Madden (p = 0.5). There were no differences in terms of vascular or nerve sections, hematomas or infections. The surgeons reported the same degree of difficulty for the two methods. CONCLUSION: The removal of the pectoralis minor muscle did not influence any of the variables studied. Therefore, either technique can be performed, at the surgeon's discretion.

Drenagem pós-esvaziamento axilar por câncer de mama: procedimento indispensável? / Wound drainage after axillary clearance for breast cancer: a mandatory procedure?

A linfadenectomia axilar constitui uma importante parte do tratamento do câncer de mama, não obstante, após essa cirurgia a paciente pode apresentar algumas complicações, sendo o seroma a mais comum. A drenagem axilar é usada para reduzir a freqüência dessa complicação e, paralelamente, gera desconforto e insegurança à paciente. O presente estudo faz uma ampla revisão sobre o tema, sugerindo que a drenagem axilar após a linfadenectomia pode ser evitada, sem prejuízos para a paciente