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BACKGROUND: Neoadjuvant chemotherapy (NACT) has arisen as a treatment option for breast cancer (BC). However, the response to NACT is still unpredictable and dependent on cancer subtype. Metabolomics is a tool for predicting biomarkers and chemotherapy response. We used plasma to verify metabolomic alterations in BC before NACT, relating to clinical data. METHODS: Liquid chromatography coupled to mass spectrometry (LC-MS) was performed on pre-NACT plasma from patients with BC (n = 75). After data filtering, an SVM model for classification was built and validated with 75%/25% of the data, respectively. RESULTS: The model composed of 19 identified metabolites effectively predicted NACT response for training/validation sets with high sensitivity (95.4%/93.3%), specificity (91.6%/100.0%), and accuracy (94.6%/94.7%). In both sets, the panel correctly classified 95% of resistant and 94% of sensitive females. Most compounds identified by the model were lipids and amino acids and revealed pathway alterations related to chemoresistance. CONCLUSION: We developed a model for predicting patient response to NACT. These metabolite panels allow clinical gain by building precision medicine strategies based on tumor stratification.
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Neoadjuvant chemotherapy (NACT) is offered to patients with operable or inoperable breast cancer (BC) to downstage the disease. Clinical responses to NACT may vary depending on a few known clinical and biological features, but the diversity of responses to NACT is not fully understood. In this study, 80 women had their metabolite profiles of pre-treatment sera analyzed for potential NACT response biomarker candidates in combination with immunohistochemical parameters using Nuclear Magnetic Resonance (NMR). Sixty-four percent of the patients were resistant to chemotherapy. NMR, hormonal receptors (HR), human epidermal growth factor receptor 2 (HER2), and the nuclear protein Ki67 were combined through machine learning (ML) to predict the response to NACT. Metabolites such as leucine, formate, valine, and proline, along with hormone receptor status, were discriminants of response to NACT. The glyoxylate and dicarboxylate metabolism was found to be involved in the resistance to NACT. We obtained an accuracy in excess of 80% for the prediction of response to NACT combining metabolomic and tumor profile data. Our results suggest that NMR data can substantially enhance the prediction of response to NACT when used in combination with already known response prediction factors.
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In 2018, WHO called for global action to eliminate cervical cancer. The complexity of the processes involved in terms of prevention is often underestimated. Low- and middle-income countries do not have a robust healthcare framework to ensure high-quality programs. The present article discusses how fragile healthcare systems are barriers to eliminating cervical cancer, and also reports the experience of a Brazilian prevention program. The article considers how cervical cancer can be interpreted as an indicator of inequality: how women's attitudes and access to care determine an early or late diagnosis, and how strategies combining vaccine and DNA-HPV tests are crucial. New vaccine schemes, the critical analysis of local data, strengthening communication, managing sentinel events, and integrating vaccination and screening data for the health information system are some of the key activities to sustainable improvement in both access and quality of care.
Assuntos
Disparidades em Assistência à Saúde , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Vacinação , Brasil/epidemiologia , Atenção à Saúde/normas , Países em Desenvolvimento , Feminino , Humanos , Programas de Rastreamento , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/prevenção & controleRESUMO
While performing aerobic exercise during chemotherapy has been proven feasible and safe, the efficacy of aerobic training on cardiorespiratory fitness (CRF) in women with breast cancer undergoing chemotherapy has not yet been systematically assessed. Therefore, the objective of this work was to determine (a) the efficacy of aerobic training to improve CRF; (b) the role of aerobic training intensity (moderate or vigorous) on CRF response; (c) the effect of the aerobic training mode (continuous or interval) on changes in CRF in women with breast cancer (BC) receiving chemotherapy. A systematic review and meta-analysis were conducted as per PRISMA guidelines, and randomized controlled trials comparing usual care (UC) and aerobic training in women with BC undergoing chemotherapy were eligible. The results suggest that increases in CRF are favored by (a) aerobic training when compared to usual care; (b) vigorous-intensity aerobic exercise (64-90% of maximal oxygen uptake, VO2max) when compared to moderate-intensity aerobic exercise (46-63% of VO2max); and (c) both continuous and interval aerobic training are effective at increasing the VO2max. Aerobic training improves CRF in women with BC undergoing chemotherapy. Notably, training intensity significantly impacts the VO2max response. Where appropriate, vigorous intensity aerobic training should be considered for women with BC receiving chemotherapy.
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One of the promising tools to evaluate collagen in the extracellular matrix is the second-harmonic generation microscopy (SHG). This approach may shed light on the biological behavior of cancers and their taxonomy, but has not yet been applied to characterize collagen fibers in cases diagnosed as invasive breast carcinoma (BC) of histological special types (IBC-ST). Tissue sections from 99 patients with IBC-ST and 21 of invasive breast carcinoma of no special type (IBC-NST) were submitted to evaluation of collagen parameters by SHG. Tissue microarray was performed to evaluate immunohistochemical-based molecular subtype. In intratumoral areas, fSHG and bSHG (forward-SHG and backward-SHG) collagen parameters achieved their lowest values in mucinous, papillary and medullary carcinomas, whereas the highest values were found in classic invasive lobular and tubular carcinomas. Unsupervised hierarchical cluster analysis and minimal spanning tree using intratumoral collagen parameters allowed the identification of three main groups of breast cancer: group A (classic invasive lobular and tubular carcinomas); group B (IBC-NST, metaplastic, invasive apocrine and micropapillary carcinomas); and group C (medullary, mucinous and papillary carcinomas). Our findings provide further characterization of the tumor microenvironment of IBC-ST. This understanding may add information to build more consistent tumor categorization and to refine prognostication.
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Neoplasias da Mama/ultraestrutura , Carcinoma/ultraestrutura , Colágeno/análise , Matriz Extracelular/ultraestrutura , Idoso , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Carcinoma/química , Carcinoma/classificação , Carcinoma/patologia , Estrogênios , Matriz Extracelular/química , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Hormônio-Dependentes/química , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Hormônio-Dependentes/ultraestrutura , Progesterona , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/ultraestruturaRESUMO
BACKGROUND: As the most incident tumor among women worldwide, breast cancer is a heterogeneous disease. Tremendous efforts have been made to understand how tumor characteristics as histological type, molecular subtype, and tumor microenvironment collectively influence disease diagnosis to treatment, which impact outcomes. Differences between populations and environmental and cultural factors have impacts on the origin and evolution of the disease, as well as the therapeutic challenges that arise due to these factors. We, then, compared copy number variations (CNVs) in mucinous and nonmucinous luminal breast tumors from a Brazilian cohort to investigate major CNV imbalances in mucinous tumors versus non-mucinous luminal tumors, taking into account their clinical and pathological features. METHODS: 48 breast tumor samples and 48 matched control blood samples from Brazilian women were assessed for CNVs by chromosome microarray. Logistic regression and random forest models were used in order to assess CNVs in chromosomal regions from tumors. RESULTS: CNVs that were identified in chromosomes 1, 5, 8, 17, 19, and 21 classify tumors according to their histological type, ethnicity, disease stage, and familial history. CONCLUSION: Copy number alterations described in this study provide a better understanding of the landscape of genomic aberrations in mucinous breast cancers that are associated with clinical features.
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Neoplasias da Mama/genética , Variações do Número de Cópias de DNA/genética , Adenocarcinoma Mucinoso/genética , Adulto , Brasil/epidemiologia , Carcinoma Ductal de Mama/genética , Estudos de Coortes , Feminino , Genômica/métodos , Humanos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Laboratory reports on adipose tissue suggest that fat grafting to the breast may pose an oncologic risk. One possible reason for this is the theoretic chronic inflammation due to adipokynes released by grafted white adipose tissue (WAT). OBJECTIVES: The aim of this study was to analyze inflammatory activity in lipofilled breast through the use of proinflammatory markers. METHODS: Fifty-four paired-breasts of female rats were divided into 4 groups: control, sham, and breasts grafted with either autologous subcutaneous (SC) WAT or autologous omentum (OM). The WAT was prepared through centrifugation, and the grafting was performed with the use of 0.9-mm blunt-tip cannula. The rats were killed 8 weeks postoperatively, and their breasts were harvested for immunohistochemical staining for CD68-expressing macrophages, gene expression (real-time PCR) for monocyte chemoattractant protein 1 (MCP-1), F4/80, Cox-2, and IL-6. RESULTS: The weights of the rats that underwent a procedure differed from those of the unmanipulated control group (P < 0.01). The macrophage counts of CD68 differed only between breasts lipofilled with OM and control (P < 0.01). MCP-1, F4/80, and Cox-2 were similarly expressed among the groups (P = 0.422, P = 0.143, and P = 0.209, respectively). The expression of IL-6 differed between breast samples grafted with SC and OM WAT (P = 0.015), but not between samples of control and OM (P = 0.752), and control and SC (P = 0.056). CONCLUSIONS: No inflammation activity was identified in the microenvironment of lipofilled breasts, indicating that chronic inflammation does not seem to be triggered by the breast lipofilling procedure.
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Gordura Abdominal/transplante , Mama/patologia , Gordura Subcutânea/transplante , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Contagem de Células , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Imuno-Histoquímica , Injeções Subcutâneas , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos/metabolismo , Modelos Animais , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo RealRESUMO
PURPOSE: We aimed to evaluate the ADNEX MR scoring system for the prediction of adnexal mass malignancy, using a simplified magnetic resonance imaging (MRI) protocol. METHODS: In this prospective study, 200 patients with 237 adnexal masses underwent MRI between February 2014 and February 2016 and were followed until February 2017. Two radiologists calculated ADNEX MR scores using an MRI protocol with a simplified dynamic study, not a high temporal resolution study, as originally proposed. Sensitivity, specificity, positive and negative predictive values, likelihood ratios, and the area under the receiver operating characteristic curve were calculated (cutoff for malignancy, score ≥ 4). The reference standard was histopathologic diagnosis or imaging findings during >12 months of follow-up. RESULTS: Of 237 lesions, 79 (33.3%) were malignant. The ADNEX MR scoring system, using a simplified MRI protocol, showed 94.9% (95% confidence interval [CI], 87.5%-98.6%) sensitivity and 97.5% (95% CI, 93.6%-99.3%) specificity in malignancy prediction; it was thus highly accurate, like the original system. The level of interobserver agreement on simplified scoring was high (κ = 0.91). CONCLUSION: In a tertiary cancer center, the ADNEX MR scoring system, even based on a simplified MRI protocol, performed well in the prediction of malignant adnexal masses. This scoring system may enable the standardization of MRI reporting on adnexal masses, thereby improving communication between radiologists and gynecologists.
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Anexos Uterinos/diagnóstico por imagem , Doenças dos Anexos/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Anexos Uterinos/anatomia & histologia , Anexos Uterinos/patologia , Doenças dos Anexos/patologia , Doenças dos Anexos/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Variações Dependentes do Observador , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos , Centros de Atenção TerciáriaRESUMO
Background: The results of experimental studies indicate that grafting of autologous adipose tissue may induce tumorigenesis at the recipient site, but clinical results do not support a carcinogenic effect of fat grafting to the breast. Objectives: The authors assessed cancer risk following transplantation of autologous fat into murine mammary tissue. Methods: In this animal study, mammary tissues from 54 breasts of 9 female rats were either grafted with autologous subcutaneous fat, grafted with autologous omental fat, or unmanipulated. Tissues were harvested and processed for histologic and immunohistochemical analyses, and the mRNA expression levels of specific genes were determined. Results: No atypia or changes in lobular structures were observed in lipofilled breasts compared with controls. The numbers of ductal cell layers and terminal ductal units were similar for lipofilled and control breasts. Macrophage concentrations also were similar for the 3 groups. The localization and magnitude of plasminogen activator inhibitor 1 were similar for lipofilled and unmanipulated breast tissue. The percentages of cells expressing Ki67 or estrogen receptor (ER) and the ER/Ki67 balance were similar for the 3 groups. Gene expression was not altered in lipofilled breasts, compared with controls. Conclusions: No theoretical risk of cancer was detected in the microenvironment of the lipofilled rat breast.
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Gordura Intra-Abdominal/transplante , Mamoplastia/efeitos adversos , Neoplasias Mamárias Experimentais/etiologia , Gordura Subcutânea/transplante , Transplante de Tecidos/efeitos adversos , Microambiente Tumoral , Animais , Mama/química , Mama/cirurgia , Carcinogênese , Feminino , Humanos , Imuno-Histoquímica , Gordura Intra-Abdominal/química , Gordura Intra-Abdominal/patologia , Antígeno Ki-67/análise , Omento , Inibidor 1 de Ativador de Plasminogênio/análise , Ratos , Ratos Sprague-Dawley , Medição de Risco , Gordura Subcutânea/patologia , Transplante Autólogo/efeitos adversosRESUMO
OBJECTIVE: This study aims to investigate the impact of digital image compression on manual and semiautomatic quantification of angiogenesis in ovarian epithelial neoplasms (including benign, borderline, and malignant specimens). DESIGN: We examined 405 digital images (obtained from a previously validated computer-assisted analysis system), which were equally divided into 5 groups: images captured in Tagged Image File Format (TIFF), low and high compression Joint Photographic Experts Group (JPEG) formats, and low and high compression JPEG images converted from the TIFF files. MEASUREMENTS: Microvessel density counts and CD34 endothelial areas manually and semiautomatically determined from TIFF images were compared with those from the other 4 groups. RESULTS: Mostly, the correlations between TIFF and JPEG images were very high (intraclass correlation coefficients >0.8), especially for low compression JPEG images obtained by capture, regardless of the variable considered. The only exception consisted in the use of high compression JPEG files for semiautomatic microvessel density counts, which resulted in intraclass correlation coefficients of <0.7. Nonetheless, even then, interconversion between TIFF and JPEG values could be successfully achieved using prediction models established by linear regression. CONCLUSION: Image compression does not seem to significantly compromise the accuracy of angiogenesis quantitation in the ovarian epithelial tumors, although low compression JPEG images should always be preferred over high compression ones.
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Compressão de Dados/métodos , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ovário/metabolismo , Ovário/patologia , Antígenos CD34/metabolismo , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Imuno-Histoquímica/instrumentação , Imuno-Histoquímica/métodosAssuntos
Neoplasias/terapia , Cuidados Paliativos , Qualidade de Vida , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Modelos Lineares , Saúde Mental , Pessoa de Meia-Idade , Análise Multivariada , Psicometria , Apoio SocialRESUMO
BACKGROUND: The objective of this study was to evaluate the correlation between the 2001 Bethesda classification of endocervical glandular abnormalities and histological diagnosis. STUDY DESIGN: A series of 155 women with endocervical glandular abnormalities on cervical smears were included: 91 with atypical glandular cells (AGC) not otherwise specified (NOS), 15 with AGC-favor neoplastic (FN); 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) as combined diagnosis and 14 with adenocarcinoma in situ (AIS). RESULTS: Histological outcome of squamous neoplasias (CIN 2 or worse) and adenocarcinoma were significantly associated with AGC-FN and AIS, taking as reference AGC-NOS, and more associated with AIS than AGC-FN. Similar associations were observed for histological outcome of adenocarcinoma, but no association was observed for only squamous neoplasia. Histological outcome of CIN2 or worse was strongly associated with AGC when HSIL was also present, but no association was observed with only for adenocarcinoma histological outcome. CONCLUSIONS: AGC-NOS, AGC-FN and AIS cytological diagnosis represent a progressively increasing association with neoplastic diagnosis, due to progressively increasing association with adenocarcinoma. Histological outcome of squamous neoplasia is frequent but does not differ with these cytological interpretations. The presence of HSIL associated with AGC represents greater probability of squamous neoplasia but not adenocarcinoma.
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Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/métodos , Displasia do Colo do Útero/diagnósticoRESUMO
OBJECTIVE: To assess the role of HPV as determinant of the incident cytological abnormalities (SIL) and cervical lesions (CIN) during a 24-month follow-up of baseline PAP smear-negative subgroup of women included in the Latin American Screening study (LAMS). STUDY DESIGN: A group of 365 women with normal Pap smear and negative or positive high-risk Hybrid Capture II test were prospectively followed-up for 24 months at Campinas and São Paulo (Brazil). The incidence rate (IR) and risk ratio (RR and 95% CI) of developing cytological or histological abnormality during the follow-up was calculated for HPV-negative and HPV-positive women. RESULTS: During the 12-month follow-up, women HPV-positive at baseline had developed a significantly higher rate of incident LSIL (IR=3.5%, RR=1.4; 95% CI 1.1-1.7) and HSIL (IR=0.7%, RR=1.5; 95% CI 1.4-1.7) abnormality. For HSIL, the IR increased to 2.1% and the RR increased to 1.7 (95% CI 1.5-1.9) among those followed for 24 months. Similarly, women with positive HPV tests were at a higher risk of developing CIN 2-3 (IR=2.6%, RR=1.5; 95% CI 1.4-1.6) during the first 12 months of follow-up, and for those followed for 24 months, this RR increased further to 1.7 (95% CI 1.5-1.9) although the IR was 0.7%. CONCLUSIONS: Oncogenic HPV infections comprise a significant risk factor for incident cervical abnormalities, and HPV test is a useful adjunct to cytology in detecting the high-risk patients among baseline PAP smear-negative women.