Delayed diagnosis and increased mortality risk: Assessing the effects of the COVID-19 pandemic on breast cancer recurrence.

OBJECTIVES: The COVID-19 pandemic has had a significant global impact since its declaration in March 2020. The COVID-19 pandemic has disproportionately impacted cancer patients, particularly those with breast cancer. This study aims to analyze the effects of the pandemic on women diagnosed with breast cancer recurrence. METHODS: A cohort study was conducted at a tertiary public hospital in São Paulo State, Brazil. Data were collected from electronic records. Patients diagnosed with breast cancer and experiencing recurrence between January 2011 and March 2022 were included. Survival analysis was performed using the Kaplan-Meier estimator and Cox regression. RESULTS: The study included 187 patients, 45 in the pandemic group (recurrence after March 23, 2020) and 142 in the pre-pandemic group. Distant recurrences were more frequent in both groups (pre-pandemic: 62.7 %, pandemic: 75.5 %). Compared to the pre-pandemic group (1.8 years), the pandemic group experienced a longer mean time to recurrence detection (2.9 years) and significantly decreased median survival (9 months vs. 22 months). The Cox regression analysis confirmed an increased risk of death for women diagnosed with breast cancer recurrence during the pandemic period (HR = 1.92, 95 % CI 1.19‒3.12). CONCLUSION: The present study is among the first to investigate the pandemic's specific effects on breast cancer recurrence, revealing concerning delays in detection and a decrease in survival rates. Prompt diagnosis, timely treatment initiation, and comprehensive support are crucial during public health crises. These findings urge healthcare systems to prioritize tailored care for breast cancer patients during pandemics.

Intestinal P-gp activity is reduced in postmenopausal women under breast cancer therapy.

Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been used as a P-gp probe, although it is important to note the involvement of other drug transporters like, OATP1B1, OATP1B3, and OATP2B1. In vitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones. The objective of this study was to investigate how intestinal P-gp activity is impacted by menopausal status. This study sampled fexofenadine plasma concentrations over 0-12 h after probe drug administration from two groups of patients with breast cancer: premenopausal (n = 20) and postmenopausal (n = 20). Fexofenadine plasma concentrations were quantified using liquid-chromatography tandem mass spectrometry. Area under the plasma concentration-time curve from zero to infinity (AUCinf ) was calculated through limited sampling strategies equation. Multiple linear regression was applied on AUCinf , maximum plasma concentration (Cmax ), and time to Cmax . Postmenopausal patients showed a significant increase in Cmax (geometric mean and 95% confidence interval [CI] 143.54, 110.95-176.13 vs. 223.54 ng/mL, 161.02-286.06 and in AUCinf 685.55, 534.98-878.50 vs. 933.54 ng·h/mL 735.45-1184.99) compared to premenopausal patients. The carriers of the ABCB1 3435 allele T displayed higher Cmax values of 166.59 (95% CI: 129.44-214.39) compared to the wild type at 147.47 ng/mL (95% CI: 111.91-194.34, p = 0.02). In postmenopausal individuals, the decrease in P-gp activity of ~40% may lead to an increased plasma exposure of orally administered P-gp substrates.

Delayed diagnosis and increased mortality risk: Assessing the effects of the COVID-19 pandemic on breast cancer recurrence

Abstract Objectives The COVID-19 pandemic has had a significant global impact since its declaration in March 2020. The COVID-19 pandemic has disproportionately impacted cancer patients, particularly those with breast cancer. This study aims to analyze the effects of the pandemic on women diagnosed with breast cancer recurrence. Methods A cohort study was conducted at a tertiary public hospital in São Paulo State, Brazil. Data were collected from electronic records. Patients diagnosed with breast cancer and experiencing recurrence between January 2011 and March 2022 were included. Survival analysis was performed using the Kaplan-Meier estimator and Cox regression. Results The study included 187 patients, 45 in the pandemic group (recurrence after March 23, 2020) and 142 in the pre-pandemic group. Distant recurrences were more frequent in both groups (pre-pandemic: 62.7 %, pandemic: 75.5 %). Compared to the pre-pandemic group (1.8 years), the pandemic group experienced a longer mean time to recurrence detection (2.9 years) and significantly decreased median survival (9 months vs. 22 months). The Cox regression analysis confirmed an increased risk of death for women diagnosed with breast cancer recurrence during the pandemic period (HR = 1.92, 95 % CI 1.19‒3.12). Conclusion The present study is among the first to investigate the pandemic's specific effects on breast cancer recurrence, revealing concerning delays in detection and a decrease in survival rates. Prompt diagnosis, timely treatment initiation, and comprehensive support are crucial during public health crises. These findings urge healthcare systems to prioritize tailored care for breast cancer patients during pandemics.

10-year opportunistic mammographic screening scenario in Brazil and its impact on breast cancer early detection: a nationwide population-based study.

Background: Mammographic screening has been used to reduce breast cancer mortality worldwide and remains the main modality for the early detection of this disease. Women from low- and middle-income countries still lack access to periodic mammograms and efficient health care. This cross-sectional study aimed to explore opportunistic mammographic coverage in Brazil, while considering the privately insured population and its association with early breast cancer (EBC) detection. Methods: Data on population, gross domestic product (GDP), number of mammograms performed under the Sistema Único de Saúde (SUS) public health system or private system, and women diagnosed with early-stage breast cancer from 2010 to 2019 were retrieved from publicly available databases. Results: A total of 39 555 636 mammograms with an average of 3 955 564 ± 395 704 mammograms were obtained per year from 2010 to 2019 in Brazil. Most examinations (58.6%) were performed in the target population (50-69 years old), while 32% were performed in women aged 40-49, and 9.4% were performed in women <40 years or >70 years of age. The 10-year mammogram coverage was 30.6% in the target population and 24.8% in the population aged 40-49 years, with significant variation across states and municipalities. The overall EBC detection rates in Brazil were 30.6% in populations aged 50-70 and 24.8% in those aged 40-50 years. We observed a positive correlation between coverage and EBC detection rate (r = 0.68; P = 0.0001 (50-70 years) and r = 0.75; P < 0.0001 (40-50 years)). According to the GDP, the municipalities with higher GDP per capita had higher mammogram coverage (P < 0.0001). Conclusions: The coverage of mammographic screening for women under the SUS is far below the international guidelines. Additionally, a significant number of mammograms have been performed in non-target populations. This scenario reflects the problematic screening programs in developing countries and reflects low rates of EBC diagnosis. As Brazil is a continental country with heterogeneous socioeconomic indicators, we observed significant variations in the number of mammograms performed by age groups when separated by states and municipalities. Even when considering supplemental health system coverage, municipalities with higher GDP per capita were associated with higher mammogram coverage.

Axillary ultrasound and fine-needle aspiration cytology to predict clinically relevant nodal burden in breast cancer patients.

BACKGROUND: Axillary lymph node involvement is one important prognostic factor in breast cancer, but the way to access this information has been modified over the years. This study evaluated if axillary ultrasound (US) coupled with fine-needle aspiration cytology (FNAC) can accurately predict clinically relevant node metastasis in patients with breast cancer, and thus assist clinical decisions METHODS: This is a cross-sectional study with retrospective data collection of 241 individuals (239 women and 2 men) with unilateral operable breast cancer who were submitted to preoperative axillary assessment by physical exam, US and FNAC if suspicious nodes by imaging. We calculated sensitivity, specificity, and accuracy of the methods. We compared the patient's characteristics using chi-square test, parametrics and non-parametrics statistics according to the variable. RESULTS: The most sensible method was US (0.59; 95% CI, 0.50-0.69), and the most specific was US coupled with FNAC (0.97; 95% CI, 0.92-0.99). Only 2.7% of the patients with normal axillary US had more than 2 metastatic nodes in the axillary lymph node dissection, against 50% of the patients with suspicious lymph nodes in the US and positive FNAC. CONCLUSIONS: Axillary US coupled with FNAC can sort patients who have a few metastatic nodes at most from those with heavy axillary burden and could be one more tool to initially evaluate patients and define treatment strategies.

A propensity score-matched case-control study of laparoscopy and laparotomy for endometrial cancer.

OBJECTIVE: A surgery is essential for the management of early endometrial carcinoma. Due to the comorbidities associated with the disease, the complications of surgery are common. Laparoscopic surgery may reduce surgical complications but also have oncological risks. We aimed to compare recurrence and overall survival (OS) associated with laparoscopy and laparotomy for early endometrial cancer. METHODS: We included women treated for presumed early endometrial carcinoma at the Clinics Hospital of Ribeirão Preto Medical School from January 1998 to December 2017. We designed a 1:2 propensity score-matched case-control and compared the patients' characteristics, short-term outcomes, recurrence, and OS. RESULTS: A total of 252 women were included in this study, 168 underwent laparotomy, and 84 underwent laparoscopy. The two groups were well balanced according to most of the variables, and obesity was a characteristic of patients in both groups. Laparoscopy was associated with increased surgical time (194.7 min vesus 165.6 min; p<0.001) and reduced rate of surgical complications (6.5% versus 0; p=0.038). Laparoscopic surgery was not associated with the risk of tumor recurrence (HR: 0.41, 95%CI 0.14-1.19, p=0.100) or all-cause mortality (HR: 0.49, 95%CI 0.18-1.35, p=0.170). CONCLUSION: Laparoscopy was safe in terms of oncological outcomes and was associated with a lower rate of surgical complications. Our data support the use of minimally invasive surgery as the preferential approach in the management of early endometrial carcinoma.

Epidemiological Analyses Reveal a High Incidence of Breast Cancer in Young Women in Brazil.

PURPOSE: Breast cancer screening is not recommended for young women (< 40 years old); therefore, those diagnosed are more likely to have advanced and metastatic disease, reducing treatment outcomes. This study aimed to investigate breast cancer epidemiology among young women in Brazil. METHODS: Data from three publicly available databases and a cohort from a university hospital in Brazil were analyzed in a retrospective study. Descriptive statistics was performed on disease prevalence and stage distribution across age groups. Incidence was estimated using age-standardized incidence ratio. The impact of age in disease-specific survival was also analyzed. RESULTS: Invasive breast cancer prevalence data by age group revealed that 4.4% and 20.6% of patients were < 35 and < 45 years old, respectively. In the United States, this prevalence was 1.85% and 11.5%, respectively (odds ratio [OR], 2.2; P < .0001). The percentage of regional and metastatic diseases were higher in São Paulo State (Fundação Oncocentro de São Paulo [FOSP]) compared with the United States (45% and 9.8% v 29% and 5.7%, respectively; P < .0001). In FOSP, regional and metastatic disease prevalence were higher among young patients (53.5% and 11.3%, respectively). The median tumor size in patients < 40 years old was higher (25.0 mm × 20.9 mm; P < .0001), and young patients have higher risk to be diagnosed with positive lymph nodes (OR, 1.5; P = .004) and higher proportion of luminal-B and triple-negative (TNBC) tumors. Young patients have a poor disease-specific survival because of late-stage diagnosis and more aggressive breast cancer subtypes (human epidermal growth factor receptor 2-enriched and TNBC) (P < .0001). CONCLUSION: In Brazil, breast cancer prevalence among young patients and late-stage incidence during this age span is higher. Advanced disease and more aggressive subtypes lead to a significant impact on breast cancer-specific survival in young patients.

Analysis of the relationship between hospital characteristics and survival in ovarian cancer: A historical cohort.

BACKGROUND AND OBJECTIVES: The management of ovarian cancer requires complex surgical and medical interventions. Specialized care is associated with superior outcomes in early and advanced stages. This study aimed to estimate the effect of hospital characteristics on the overall survival of women with epithelial ovarian cancer. METHODS: We established a cohort with data recorded by the Fundação Oncocentro de São Paulo cancer registry. We included 6111 women treated for ovarian cancer in the state of Sao Paulo from January 2000 to December 2018. From 76 hospitals analyzed, 7 were high volume (20 or more cases a year) and 69 low volume. Twenty-nine were teaching and 47 community hospitals. A 10-year survival was analyzed using the Kaplan-Meyer estimator and the Cox model. RESULTS: Fifty-two percent of the epithelial ovarian cancer patients were treated in high-volume hospitals. High-volume - (HR, 0.86; 95% CI, 0.8-0.92; P < .001) and teaching - (HR, 0.91; 95% CI, 0.85-0.99; P = .019) were hospital characteristics associated with low risk of death in 10 years. CONCLUSIONS: High-volume and teaching hospitals are associated with better overall survival in ovarian cancer. Our data suggest that both hospital characteristics are important indicators of good quality of care in ovarian cancer treatment.

Total, renal and hepatic clearances of doxorubicin and formation clearance of doxorubicinol in patients with breast cancer: Estimation of doxorubicin hepatic extraction ratio.

Doxorubicin (DOX) is a cytotoxic drug which has remained as an essential component of chemotherapy regiment for breast cancer. The cardiotoxicity of DOX is related to the accumulation of its main metabolite doxorubicinol (DOXOL) in the cardiac tissue. Although the pharmacokinetics of DOX shows high interindividual variability, there are no significant covariates to improve dose adjustment. The present study reports the pharmacokinetics of both DOX and DOXOL in a homogeneous population of young female patients with breast cancer (n = 12) making use of a standardized drug association, evaluated in the very first chemotherapy cycle, using plasma and urine data that allowed the calculation of the renal clearance of DOX, the formation clearance of DOXOL and the hepatic clearance of DOX. The extensive data availability also made it possible to estimate the hepatic extraction ratio of DOX for the investigated population, as well as to determine DOXOL unbound fraction in plasma for the first time in humans. DOX and DOXOL simultaneous analysis in plasma, plasma ultrafiltrate, and urine were performed by liquid chromatography coupled to mass spectrometry (LC-MS/MS). The pharmacokinetics profile of both DOX and DOXOL showed high variability (geometric coefficient of variation of area under the plasma concentration versus time curve extrapolated to infinity was approximately 215 %). The geometrics means were 0.26 for DOXOL/DOX AUC ratio, 15 % and 17 % for unbound fractions of DOX and DOXOL, respectively, 30.70 L⋅h-1 for total clearance, 0.66 L⋅h-1 for renal clearance, 29.97 L⋅h-1 for hepatic clearance and 0.39 L⋅h-1 for the formation clearance of the metabolite DOXOL. The 95 % confidence interval of the estimated hepatic extraction ratio of DOX ranged from 0.14 to 0.79, which characterizes DOX as a drug of low, intermediate or high hepatic extraction ratio.

Hormonal status affects plasma exposure of tamoxifen and its main metabolites in tamoxifen-treated breast cancer patients.

BACKGROUND: Tamoxifen is considered a prodrug of its active metabolite endoxifen, which is dependent on the CYP2D6 and CYP3A enzymes. Tamoxifen pharmacokinetic variability influences endoxifen exposure and, consequently, its clinical outcome. This study investigated the impact of hormonal status on the pharmacokinetics of tamoxifen and its metabolites in TAM-treated breast cancer patients. METHODS: TAM-treated breast cancer patients (n = 40) previously believed to have CYP3A activity within the normal range based on oral midazolam and phenotyped as CYP2D6 normal metabolizers using oral metoprolol were divided into two groups according to premenopausal (n = 20; aged 35-50 years) or postmenopausal (n = 20; aged 60-79 years) status. All patients were treated with 20 mg/day tamoxifen for at least three months. Serial plasma samples were collected within the 24 h dose interval for analysis of unchanged tamoxifen, endoxifen, 4-hydroxytamoxifen and N-desmethyltamoxifen quantified by LC-MS/MS. CYP activities were assessed using midazolam apparent clearance (CYP3A) and the metoprolol/alfa-hydroxymetoprolol plasma metabolic ratio (CYP2D6). CYP3A4, CYP3A5 and CYP2D6 SNPs and copy number variation were investigated using TaqMan assays. RESULTS: Postmenopausal status increased steady-state plasma concentrations (Css) of tamoxifen (116.95 vs 201.23 ng/mL), endoxifen (8.01 vs 18.87 ng/mL), N-desmethyltamoxifen (485.16 vs 843.88 ng/mL) and 4-hydroxytamoxifen (2.67 vs 4.11 ng/mL). The final regression models included hormonal status as the only predictor for Css of tamoxifen [ß-coef ± SE, p-value (75.03 ± 17.71, p = 0.0001)] and 4-hydroxytamoxifen (1.7822 ± 0.4385, p = 0.0002), while endoxifen Css included hormonal status (8.578 ± 3.402, p = 0.02) and race (11.945 ± 2.836, p = 0.007). For N-desmethyltamoxifen Css, the final model was correlated with hormonal status (286.259 ± 76.766, p = 0.0007) and weight (- 8.585 ± 3.060, p = 0.008). CONCLUSION: The premenopausal status was associated with decreased endoxifen plasma concentrations by 135% compared to postmenopausal status. Thus, the endoxifen plasma concentrations should be monitored mainly in the premenopausal period to maintain plasma levels above the efficacy threshold value. TRIAL REGISTRATION: RBR-7tqc7k.

Prognostic factors for response to chemotherapy in advanced tumors of the uterine cervix: the role of neoangiogenesis. / Fatores prognósticos de resposta à quimioterapia em tumores avançados do colo uterino: o papel da neoangiogênese.

OBJECTIVE: to analyze the expression of Vascular Endothelial Growth Factor (VEGF), its receptor (VEGFR-2), age and histological type of advanced cervical carcinomas with respect to the clinical response to neoadjuvant chemotherapy. METHODS: we studied 40 patients with cervical carcinoma (IB2 and IVA) diagnosed by biopsies prior to treatment. All patients underwent neoadjuvant chemotherapy and evaluation for clinical response and expression of VEGF. We considered a tumor regression greater than 50% as a good clinical response. RESULTS: eighteen patients (45%) had good response to chemotherapy, and 22 (55%), poor response. VEGF expression was positive in 16 patients and negative in 24. When analyzed separately for response to chemotherapy, only the positive expression of VEGF was associated with good clinical response (p=0.0157). CONCLUSION: VEGF expression alone was an important marker of good response to neoadjuvant chemotherapy in patients with advanced carcinoma of the cervix.

OBJETIVO: analisar a expressão do Fator de Crescimento do Endotélio Vascular (VEGF), seu receptor (VEGFR-2), idade e tipo histológico de carcinomas avançados de colo uterino com relação à resposta clínica à quimioterapia neoadjuvante. MÉTODOS: foram incluídas 40 pacientes com diagnóstico de carcinoma de colo uterino (IB2 e IVA), com biópsias prévias ao tratamento. Todas as pacientes foram submetidas à quimioterapia neoadjuvante e avaliadas quanto à resposta clínica e à expressão do VEGF. Considerou-se boa resposta clínica uma regressão tumoral total ou maior do que 50%. RESULTADOS: em relação à resposta à quimioterapia, 18 pacientes (45%) apresentaram boa resposta e 22 (55%), má resposta. Quanto à expressão do VEGF, em 16 pacientes foi considerada positiva e em 24, negativa. Quando os casos foram analisados separadamente em relação à resposta à quimioterapia, somente a expressão positiva de VEGF foi associada à boa resposta clínica (p=0,0157). CONCLUSÃO: a expressão de VEGF mostrou ser isoladamente, um importante marcador de boa resposta ao tratamento quimioterápico neoadjuvante das pacientes com carcinoma avançado de colo uterino.

Fatores prognósticos de resposta à quimioterapia em tumores avançados do colo uterino: o papel da neoangiogênese / Prognostic factors for response to chemotherapy in advanced tumors of the uterine cervix: the role of neoangiogenesis

RESUMO Objetivo: analisar a expressão do Fator de Crescimento do Endotélio Vascular (VEGF), seu receptor (VEGFR-2), idade e tipo histológico de carcinomas avançados de colo uterino com relação à resposta clínica à quimioterapia neoadjuvante. Métodos: foram incluídas 40 pacientes com diagnóstico de carcinoma de colo uterino (IB2 e IVA), com biópsias prévias ao tratamento. Todas as pacientes foram submetidas à quimioterapia neoadjuvante e avaliadas quanto à resposta clínica e à expressão do VEGF. Considerou-se boa resposta clínica uma regressão tumoral total ou maior do que 50%. Resultados: em relação à resposta à quimioterapia, 18 pacientes (45%) apresentaram boa resposta e 22 (55%), má resposta. Quanto à expressão do VEGF, em 16 pacientes foi considerada positiva e em 24, negativa. Quando os casos foram analisados separadamente em relação à resposta à quimioterapia, somente a expressão positiva de VEGF foi associada à boa resposta clínica (p=0,0157). Conclusão: a expressão de VEGF mostrou ser isoladamente, um importante marcador de boa resposta ao tratamento quimioterápico neoadjuvante das pacientes com carcinoma avançado de colo uterino.

ABSTRACT Objective: to analyze the expression of Vascular Endothelial Growth Factor (VEGF), its receptor (VEGFR-2), age and histological type of advanced cervical carcinomas with respect to the clinical response to neoadjuvant chemotherapy. Methods: we studied 40 patients with cervical carcinoma (IB2 and IVA) diagnosed by biopsies prior to treatment. All patients underwent neoadjuvant chemotherapy and evaluation for clinical response and expression of VEGF. We considered a tumor regression greater than 50% as a good clinical response. Results: eighteen patients (45%) had good response to chemotherapy, and 22 (55%), poor response. VEGF expression was positive in 16 patients and negative in 24. When analyzed separately for response to chemotherapy, only the positive expression of VEGF was associated with good clinical response (p=0.0157). Conclusion: VEGF expression alone was an important marker of good response to neoadjuvant chemotherapy in patients with advanced carcinoma of the cervix.

Weight Gain during Systemic Oncologic Therapy for Breast Cancer: Changes in Food Intake and Physical Activity / Ganho Ponderal durante o Tratamento Oncológico Sistêmico para Câncer de Mama: Mudanças na Ingestão Alimentar e na Atividade Física / Aumento de Peso durante el Tratamiento Oncológico Sistémico para Cáncer de Mama: Cambios en la Ingestión de Alimentos y Actividad Física

Introduction: Weight gain frequently occurs during treatment for breast cancer. Objective: To evaluate changes in dietary intake and physical activity in the weight evolution of women on systemic oncologic treatment for breast cancer. Method: The prospective and comparative study included 89 women submitted to systemic oncologic treatment for breast cancer, grouped according to the occurrence of weight gain in relation to body weight documented before beginning treatment. Patients were classified as 1) Group with weight gain (those with an increase in body weight greater than or equal to 2% over pre-treatment weight); 2) Group without weight gain (those who maintained or lost weight during treatment). We calculated body mass index (BMI) of patients and analyzed their body composition by bioelectrical impedance (BIA). Changes in food intake, gastrointestinal symptoms, and physical activity level, as well as reductions in muscle and fat mass, were documented. Results:Tumor staging (p=0.24), use of antineoplastic drugs (p=0.23) and intention of treatment (p=0.61) were no different between the weight gain group (n=36) and no weight gain group (n=53). No difference was found in anthropometric and BIA data between the groups during oncologic treatment. Frequency of gastrointestinal symptoms was not different between the groups. However, increased food intake and bed rest, and a decrease in physical activity level were more frequent among women who gained weight during therapy. Conclusions: Weight gain in women undergoing systemic oncologic therapy for breast cancer may be, at least in part, caused by higher energy intake and lower physical activity.

Introdução: O ganho ponderal ocorre com frequência durante o tratamento oncológico para o câncer de mama. Objetivo: Avaliar as mudanças da ingestão alimentar e da atividade física na evolução ponderal de mulheres sob tratamento oncológico sistêmico para câncer de mama. Método: Estudo prospectivo e comparativo que incluiu 89 mulheres submetidas a tratamento oncológico sistêmico para neoplasia mamária, agrupadas de acordo com a ocorrência de aumento ponderal em relação ao peso corporal documentado antes do início do tratamento. As pacientes foram classificadas em 1) Grupo com ganho ponderal (aumento ≥2% em relação ao peso pré-tratamento); 2) Grupo sem ganho ponderal (ganho ou manutenção do peso durante o tratamento). O índice de massa corporal foi calculado e a composição corporal foi determinada por impedância bioelétrica. Foram documentadas mudanças na ingestão de alimentos e no padrão de atividade física, queixas digestivas e alterações da massa corporal muscular e adiposa. Resultados: Os grupos com ganho ponderal (n=36) e sem ganho ponderal (n=53) foram semelhantes quanto ao estadiamento tumoral (p=0,24), emprego das classes de drogas antineoplásicas (p=0,23) e modalidade de tratamento oncológico (p=0,61). Durante o tratamento oncológico sistêmico, a composição corporal foi semelhante entre os grupos de estudo. Comparadas com o grupo sem ganho de peso, houve maior proporção de aumento na ingestão alimentar e de restrição na atividade física entre as mulheres que ganharam peso. Conclusão: O ganho ponderal em mulheres com neoplasia mamária em tratamento oncológico sistêmico pode ser atribuído à maior ingestão energética e à redução na atividade física.

Introducción: El aumento de peso es frecuente durante el tratamiento oncológico para el cáncer de mama. Objetivo: Evaluar los cambios de la ingesta alimentaria y de la actividad física en la evolución ponderal de las mujeres en tratamiento oncológico sistémico para el cáncer de mama. Método: El estudio prospectivo y comparativo incluyó 89 mujeres sometidas a tratamiento sistémico oncológico por neoplasia mamaria, agrupadas de acuerdo con la ocurrencia de aumento ponderal en relación al peso corporal al início del tratamiento. Las pacientes fueron clasificadas en 1) Grupo con ganancia ponderal (≥2% en relación al peso pretratamiento); 2) Grupo sin ganancia ponderal (mantenimiento o pérdida de peso durante el tratamiento). El índice de masa corporal fue calculado y la composición corporal fue determinada por impedancia bioeléctrica. Fueron documentadas las variaciones en la ingestión de alimentos y el patrón de actividad física, quejas digestivas y redución en la masa corporal. Resultados: Los grupos con ganancia ponderal (n=36) y sin ganancia ponderal (n=53) fueron semejantes cuanto a estadificación tumoral (p=0,24), empleo de medicamentos antineoplásicos (p=0,23) y modalidad del tratamiento oncológico (p=0,61). Durante el tratamiento oncológico, la composición corporal fue semejante entre los grupos de estudio. Comparados con el grupo sin aumento de peso, se observó aumento en la ingestión de alimentos y restricción en la actividad física entre las mujeres que ganaron peso. Conclusión: El aumento de peso en mujeres sometidas a tratamiento oncológico para cáncer de mama, puede ser atribuido a mayor ingestión energética y reducción de actividad física.

Development of New Formulations of Biologics: Expectations, Immunogenicity, and Safety for Subcutaneous Trastuzumab.

Subcutaneous (SC) trastuzumab has long been approved as a cancer treatment for early and advanced HER2-positive (HER2+) breast cancer by both the European Medicines Agency (EMA) and Agência Nacional de Vigilância Sanitária (ANVISA), the Brazilian National Health Surveillance Agency. A pivotal non-inferiority phase III trial, which aimed to provide a more convenient and cost-effective treatment in the HER2+ breast cancer neoadjuvant setting, showed that the SC group met prespecified efficacy endpoints and the SC formulation was considered as safe as the intravenous (IV) formulation. Considering the recent approval of several biosimilars, new SC formulations are also an interesting manufacturer strategy as these drugs can obtain patent protection. Despite being considered non-inferior to the IV formulation of trastuzumab, in clinical development, the SC formulation elicited higher immunogenicity, mainly related to overall anti-drug antibodies (ADAs); however, this finding was classified as clinically non-significant. In this article, we explore different aspects of the benefits and risks of the SC trastuzumab formulation according to published data.

Identification of a Subtype of Poorly Differentiated Invasive Ductal Carcinoma of the Breast Based on Vimentin and E-cadherin Expression.

OBJECTIVE: The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs). METHODS: We have constructed a tissue microarray (TMA) from 87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B (n = 39), HER2 enriched (n = 25), and triple-negative (TNBC) (n = 23), based on the IHC expression. RESULTS: We have observed that luminal A and B tumors lack the VIM+/CDH1-/low phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors (p = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM+/CDH1-/low phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) (p = 0.02). The median Ki67 index in the VIM+/CDH1-/low tumors was 13.6 (range: 17.8-45.4) compared with 9.8 (range: 4.1-38.1) in other tumors (p = 0.0007). The presence of lymph node metastasis was less frequent in patients with VIM+/CDH1-/low tumors (23% versus 61%; X2 test; p = 0.01). CONCLUSION: Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index.

OBJETIVO: O uso de marcadores moleculares pode identificar subtipos tumorais com diferentes taxas de recidiva. O objetivo do presente estudo é caracterizar a expressão imunohistoquímica da vimentina (VIM), da E-caderina (CDH1) e de CK5 em pacientes com carcinoma ductal invasivo (CDI) da mama. MéTODOS: Utilizamos uma matriz de amostras teciduais (TMA, na sigla em inglês) de 87 pacientes com CDI da mama. Para avaliar a expressão dos receptores de estrogênio (RE) e receptores de progesterona (RP), HER2, VIM, CDH1, CK5 e Ki67, utilizamos imunohistoquímica. Os tumores foram classificados como luminal A e B (n = 39), HER2+ (n = 25) e triplo negativo (TNBC) (n = 23). RESULTADOS: Foi observado que tumores luminais A e B não expressaram o fenótipo VIM+/CDH1-/low. Este fenótipo foi observado em 16,5% dos tumores HER2+ e em 60% dos tumores TNBC (p = 0,0001). Dos 20 tumores TNBC, a CK5 (marcador de tumor basalóide) foi super expressa em 11 amostras. O fenótipo VIM+/CDH1-/low foi observado em 5 tumores CK5+ TNBC (45%) e em 7 dos 9 tumores CK5- TNBC (78%) (p = 0,02). A expressão média de Ki67 nos tumores VIM+/CDH1-/low foi 13.6 (amplitude de 17,8 a 45,4) comparado com 9,8 (amplitude de 4,1 a 38,1) nos outros tumores (p = 0,0007). A presença de metástase linfonodal foi menor em tumores com fenótipo VIM+/CDH1-/low (23% contra 61%; teste X2 ; p = 0,01). CONCLUSãO: Nossos achados sugerem que a expressão de VIM e CDH1 pode identificar um subtipo de CDI da mama com fenótipo mesenquimal associado a pior prognóstico, lesões de alto grau e alto índice mitótico.

Increased STAT1 Expression in High Grade Serous Ovarian Cancer Is Associated With a Better Outcome.

OBJECTIVE: Recently it has been demonstrated that constitutively activated signal transducer and activator of transcription 1 (STAT1) gene expression may act as a biomarker of ovarian cancer chemotherapy response. In this study, our objective was to validate the use of STAT1 immunohistochemistry as a prognostic biomarker for disease outcome using a cohort derived from Latin America. METHODS: We evaluated a cohort of Brazilian high-grade serous ovarian cancer, comprising 65 patients with outcome data covering more than 5 years to determine the prognostic and predictive value of STAT1 expression levels. High-grade serous ovarian cancer tumors were used to construct a tissue microarray. Exploratory analyses were conducted on clinical, histopathological, and STAT1 expression data that included descriptive statistics and Pearson correlative analyses. Survival curves for disease-free survival and overall survival were obtained by the Kaplan-Meier method, and the significance of homogeneity between the classes was assessed by log-rank statistics (Mantel-Cox). RESULTS: High expression of STAT1 in tumors was significantly associated with improved disease-free survival (P = 0.0256) and overall survival (P = 0.0193). Proportional hazards regression analysis showed STAT1 expression had an independent effect on both disease-free survival (P = 0.0358) and overall survival (P = 0.0469). CONCLUSIONS: These findings from a Brazilian cohort of patients with ovarian cancer reinforce the association of high STAT1 expression with better response to chemotherapy, providing additional validation of this protein as both a prognostic and predictive biomarker. Collectively, these results together with other recently published studies increase the feasibility of using the STAT1 pathway for the development of novel immunomodulator drugs that could enhance response to treatment.

Quality of Life in Women With Breast Cancer Treated With or Without Chemotherapy.

BACKGROUND: The diagnosis and treatment of breast cancer may negatively affect the quality of life (QOL) of women. OBJECTIVES: The aim of this study is to assess QOL in women with breast cancer who were treated with or without chemotherapy and to identify factors associated with improved or worsening QOL in these women. METHODS: This cross-sectional study enrolled 112 women who were treated with chemotherapy (CTX group, with 85 [75.9%] women) or without chemotherapy (non-CTX group, with 27 [24.1%] women) for breast cancer. The Short-Form Health Survey (SF-36) assessed QOL and the Hospital Anxiety and Depression scale assessed anxiety and depression. RESULTS: The overall mean SF-36 score was below 50 in all domains. Relative to CTX women, non-CTX women were significantly older (P = .001) and more likely to engage in physical exercise (P = .002). The non-CTX group had higher scores in the Physical Functioning (P = .001) and Role-Physical (P = .0009) domains of the SF-36 relative to the CTX group, and the fluoruracil + epirubicin + cyclophosphamide group had significantly lower scores in the SF-36 domains Physical Functioning (P = .009) and Role-Physical (P = .02). CONCLUSION: Chemotherapy treatment for breast cancer worsens QOL in the Physical Functioning and the Role-Physical domains of the SF-36 relative to women treated without chemotherapy. IMPLICATIONS FOR PRACTICE: Nurses should assess Physical Functioning and the Role-Physical before treatment, as a woman who was not physically active before breast cancer is not likely to become physically active after treatment. Establishing support groups and providing educational sessions about the disease and its management, supportive care can improve the QOL of this population.

Cervical cancer: what's new? / Câncer de colo do útero: o que há de novo?

SUMMARY Cervical cancer is the most common gynecological cancer in Brazil. Among women, it is the second most frequent, second only to breast cancer. It is the fourth leading cause of cancer death in the country, with estimated 15,590 new cases (2014) and 5,430 deaths (2013). In order to update information to improve outcomes, reduce morbidity and optimize the treatment of this cancer, this article will address the advancement of knowledge on cervical cancer. The topics covered include the role of surgery in different stages, treatment of locally advanced carcinomas, fertility preservation, the role of the sentinel lymph node technique, indications and techniques of radiotherapy and chemotherapy, and some special situations.

RESUMO O câncer de colo uterino é o câncer ginecológico mais frequente em nosso meio. Entre as mulheres, é o segundo mais frequente, atrás apenas do câncer de mama. É a quarta causa de morte por câncer no Brasil, com estimativa de 15.590 casos novos (2014) e com 5.430 mortes (2013). No intuito de atualizar informações para a melhora do prognóstico, redução da morbidade e otimização do tratamento dessa neoplasia, serão abordados neste artigo os avanços nos conhecimentos sobre o câncer cervical. Entre os temas apresentados, estão o papel da cirurgia nos diferentes estádios, o tratamento dos carcinomas localmente avançados, a preservação da fertilidade, o papel da técnica do linfonodo sentinela, indicações e técnicas da radio e quimioterapia, além de situações especiais.

Detection of human mammaglobin A mRNA in peripheral blood of breast cancer patients before treatment and association with metastasis.

BACKGROUND: Mammaglobin A (MGA), mainly expressed in the breast epithelium, is overexpressed in breast cancer, and has been established as a tumor and promissory marker for the early detection of metastasis. AIM: The main aim of this study was to evaluate the association between the presence of the MGA transcript in the peripheral blood of Brazilian breast cancer patients and healthy women and the development of breast cancer and tumor progression. MATERIAL AND METHODS: The expression of the MGA transcript in peripheral blood of 102 breast cancer patients and 102 healthy women was assessed by RT-PCR. RESULTS: MGA mRNA was expressed in the peripheral blood of 39 breast cancer patients and in none of the women from the control group. The presence of MGA was significantly associated with presence of metastasis and age at onset after 60 years. The presence of MGA mRNA in peripheral blood displayed a sensitivity of 38.2%, specificity of 100.0%, positive predictive value (PPV) of 100.0%, and negative predictive value (NPV) of 61.8% as a breast cancer marker. CONCLUSION: This study provides additional evidence of the presence of MGA in the peripheral blood of breast cancer patients, and its applicability as an efficient biomarker for breast cancer (High specificity and PPV). To our knowledge, this is the first study to assess the expression of MGA mRNA in peripheral blood obtained from the Brazilian population.