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.

The contribution and perspectives of proteomics to uncover ovarian cancer tumor markers.

Despite all the advances in understanding the mechanisms involved in ovarian cancer (OC) development, many aspects still need to be unraveled and understood. Tumor markers (TMs) are of special interest in this disease. Some aspects of clinical management of OC might be improved by the use of validated TMs, such as differentiating subtypes, defining the most appropriate treatment, monitoring the course of the disease, or predicting clinical outcome. The Food and Drug Administration (FDA) has approved a few TMs for OC: CA125 (cancer antigen 125; monitoring), HE4 (Human epididymis protein; monitoring), ROMA (Risk Of Malignancy Algorithm; HE4+CA125; prediction of malignancy) and OVA1 (Vermillion's first-generation Multivariate Index Assay [MIA]; prediction of malignancy). Proteomics can help advance the research in the field of TMs for OC. A variety of biological materials are being used in proteomic analysis, among them tumor tissues, interstitial fluids, tumor fluids, ascites, plasma, and ovarian cancer cell lines. However, the discovery and validation of new TMs for OC is still very challenging. The enormous heterogeneity of histological types of samples and the individual variability of patients (lifestyle, comorbidities, drug use, and family history) are difficult to overcome in research protocols. In this work, we sought to gather relevant information regarding TMs, OC, biological samples for proteomic analysis, as well as markers and algorithms approved by the FDA for use in clinical routine.

The impact of chemotherapeutic treatment on the oral microbiota of patients with cancer: a systematic review.

OBJECTIVE: Chemotherapy is a type of systemic treatment that inhibits neoplastic cells (cancer cells), produces immunosuppression, and may lead to changes in the oral mucosa and, consequently, in the oral microbiota. The aim of this systematic review was to analyze, in the scientific literature, evidence of the impact of chemotherapy on the oral microbiota. STUDY DESIGN: The authors conducted a search in PubMed/MEDLINE, Scientific Electronic Library Online (SciELO), LILACS, ScienceDirect, Web of Science, and Cochrane Library; to identify studies that discussed change in the oral microbiota of patients with during chemotherapy. Articles published in English until July 2017 were included. The quality of a study was assessed by using the Ottawa-Newcastle scale. RESULTS: Of 5252 articles potentially relevant to this review, 17 were included in this study. Of the 17 studies included, 16 had used culture techniques, and 1 had used genetic sequencing. The most frequently observed bacteria were aerobic gram-negative (Klebsiella spp., Escherichia coli, Enterobacter, Pseudomonas spp.), anaerobic gram-negative (Veillonella spp., Capnocytophaga), and gram-positive bacteria (Streptococcus spp., Staphylococcus spp.). CONCLUSIONS: During chemotherapy, patients with cancer present a more complex oral microbiota under favorable conditions for their development during immunosuppression, and these may be responsible for different serious local or systemic pathologies.

Effects of the Metallic Port in Tissue Expanders on Dose Distribution in Postmastectomy Radiotherapy: A Tridimensional Experimental Model of Dosimetry in Breast Reconstruction.

The purpose of this research was to develop an experimental model of dosimetry using a breast phantom and evaluate the effects of the metallic port in tissue expanders on dose distribution in postmastectomy radiotherapy. Dose distribution was assessed using an experimental acrylic dosimetry simulator in the absence and presence of a metallic disc (MD), which is similar to that used in tissue expanders containing a magnetic port, by collecting coronal and sagittal radiochromic films. Dosimetry film analysis did not show any changes in dose distribution, except for a MD shadow in the sagittal film where the dose distribution rate was on average 14% lower than in other areas. This model very closely resembled actual breast reconstruction with a tissue expander containing a magnetic port. Scattering or attenuation of the irradiation dose due to interference of the MD was not evident in areas that could jeopardize the effectiveness of radiation therapy. Therefore, the presence of the MD inside the tissue expander does not likely have an impact on radiotherapy effectiveness during immediate breast reconstruction.

Alteration of Blood Circulation in the Upper Limb Before and After Surgery for Breast Cancer Associated with Axillary Lymph Node Dissection or Sentinel Lymph Node Biopsy.

BACKGROUND: This aim of this study was to assess and compare arterial and venous circulation in women with axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) before and after breast cancer surgery. METHODS AND RESULTS: Fifty-two women took part in the study, divided into three groups: those undergoing ALND at levels I, II, and III (ALNDG), with mean age of 56.29 ± 10.85 years old; those undergoing sentinel lymph node biopsy (SLNBG), with mean age of 57.7 ± 7.07 years old; and controls without diagnosis of breast cancer (CG), with mean age of 53.92 ± 8.85 years old. Maximum venous and arterial flow velocities in upper limbs were assessed before and after surgical treatment for breast cancer by means of Doppler ultrasonography (Nicolet Vascular Versalab SE®). Data normality was assessed by using the Shapiro-Wilk's test, with normally distributed variables being analyzed with analysis of variance (ANOVA) and post hoc Tukey's test or t-test. For variables with non-normal distribution, Kruskal-Wallis' test and post hoc Dunn's test were used at p < 0.05. There was significant difference in the maximum blood flow velocities, both venous (ALNDG) and arterial (SLNBG). CONCLUSION: The results suggest that ALND and SLNB can interfere with the upper limp blood circulation.

Accuracy and Reliability of Infrared Thermography in Assessment of the Breasts of Women Affected by Cancer.

Evaluate reliability and accuracy of infrared thermography in the assessment of women wth breasts cancer. Thirty-five participants had unilateral breast cancer and 17 control subjects were assessed using infrared thermography. To evaluate reliability, two professionals, who were experienced, measured the temperature of the infrared images in two different moments, with a one-week interval. Biopsy was used as a gold standard exam with regard identify breast cancer. The analysis illustrated excellent reliability in terms of the affected, contralateral and control breasts with the intra-class correlation coefficient values ranging from 0.948 to 0.999. Standard measurement error ranged from 0.04 to 0.28 °C, and minimum detectable change deviated from 0.11 to 0.78 °C. Moreover, low to moderate accuracy were observed in terms of the establishment of the breast cancer diagnosis with values of the area under the receiver operating characteristic (ROC) curve ranging from 0.571 and 0.749. Breasts affected by cancer present higher skin temperature compared to contralateral and control. Furthermore, excellent reliability of the analysis of the infrared images and low-moderate accuracy in terms diagnosis were observed. Considering the results, infrared thermography can be applied as an instrument complement the assessment of breast cancer patients, but not for diagnostic purposes.

Supervised physical therapy in women treated with radiotherapy for breast cancer.

OBJECTIVE: to evaluate the effect of physical therapy on the range of motion of the shoulders and perimetry of the upper limbs in women treated with radiotherapy for breast cancer. METHODS: a total of 35 participants were randomized into two groups, with 18 in the control group (CG) and 17 in the study group (SG). Both of the groups underwent three evaluations to assess the range of motion of the shoulders and perimetry of the upper limbs, and the study group underwent supervised physical therapy for the upper limbs. RESULTS: the CG had deficits in external rotation in evaluations 1, 2, and 3, whereas the SG had deficits in flexion, abduction, and external rotation in evaluation 1. The deficit in abduction was recovered in evaluation 2, whereas the deficits in all movements were recovered in evaluation 3. No significant differences in perimetry were observed between the groups. CONCLUSION: the applied supervised physical therapy was effective in recovering the deficit in abduction after radiotherapy, and the deficits in flexion and external rotation were recovered within two months after the end of radiotherapy. Registration number of the clinical trial: NCT02198118. OBJETIVO: avaliar o efeito da fisioterapia na amplitude de movimento do ombro e na perimetria do membro superior, aplicada durante o período da radioterapia nas mulheres em tratamento para o câncer de mama. MÉTODOS: 35 voluntárias foram randomizadas em dois grupos, 18 para o grupo controle e 17 para o grupo de estudo. Os dois grupos foram submetidos a três avaliações da amplitude de movimento do ombro e perimetria do membro superior, sendo o grupo de estudo também submetido à fisioterapia supervisionada para os membros superiores. RESULTADOS: o grupo controle apresentou déficit entre os membros para o movimento de rotação externa nas avaliações 1, 2 e 3. O grupo de estudo apresentou déficit entre os membros para os movimentos de flexão, abdução e rotação externa na avaliação 1. Houve recuperação do déficit de movimento de abdução na avaliação 2 e, na avaliação 3, os déficits de todos os movimentos estavam recuperados. Na análise da perimetria não foi observada diferença significativa. CONCLUSÃO: o protocolo fisioterapêutico supervisionado aplicado foi efetivo na recuperação do déficit de abdução pós-radioterapia e de flexão e rotação externa quando avaliados até 2 meses após o término da radioterapia. Número do registro do ensaio clínico: NCT02198118. OBJETIVO: evaluar el efecto de la terapia física en el rango de movimiento de los hombros y la perimetría de las extremidades superiores en mujeres tratadas con radioterapia debido a cáncer de mama. MÉTODOS: un total de 35 participantes fueron aleatorizadas en dos grupos, 18 en el grupo control y 17 en el grupo de estudio. Ambos grupos fueron sometidos a tres evaluaciones para evaluar el rango de movimiento de los hombros y la perimetría de las extremidades superiores, y el grupo de estudio fue sometido a terapia física supervisada de las extremidades superiores. RESULTADOS: el grupo de control tuvo déficits en la rotación externa en la evaluación 1, 2, y 3, mientras que el grupo de estudio tuvo déficits en la flexión, abducción y rotación externa en la evaluación 1. El déficit en la abducción fue recuperado en la evaluación 2, mientras que los déficits en todos los movimientos fueron recuperados en la evaluación 3. No se observaron diferencias significativas en la perimetría. CONCLUSIÓN: la terapia física supervisada aplicada fue efectiva en la recuperación del déficit en la abducción después de la radioterapia y los déficits en flexión y rotación externa fueron recuperados dos meses después de terminada la radioterapia. Número de registro del ensayo clínico: NCT02198118.

A proteomic signature of ovarian cancer tumor fluid identified by highthroughput and verified by targeted proteomics.

UNLABELLED: Tumor fluid samples have emerged as a rich source for the identification of ovarian cancer in the context of proteomics studies. To uncover differences among benign and malignant ovarian samples, we performed a quantitative proteomic study consisting of albumin immunodepletion, isotope labeling with acrylamide and in-depth proteomic profiling by LC-MS/MS in a pool of 10 samples of each histological type. 1135 proteins were identified, corresponding to 505 gene products. 223 proteins presented associated quantification and the comparative analysis of histological types revealed 75 differentially abundant proteins. Based on this, we developed a panel for targeted proteomic analysis using the multiple reaction monitoring (MRM) method for validation of 51 proteins in individual samples of high-grade serous ovarian tumor fluids (malignant) and benign serous cystadenoma tumor fluids. This analysis showed concordant results in terms of average amounts of proteins, and APOE, SERPINF2, SERPING1, ADAM17, CD44 and OVGP1 were statistically significant between benign and malignant group. The results observed in the MRM for APOE were confirmed by western blotting, where APOE was more abundant in malignant samples. This molecular signature can contribute to improve tumor stratification and shall be investigated in combination with current biomarkers in larger cohorts to improve ovarian cancer diagnosis. BIOLOGICAL SIGNIFICANCE: Despite advances in cancer research, ovarian cancer has a high mortality and remains a major challenge due to a number of particularities of the disease, especially late diagnosis caused by vague clinical symptoms, the cellular and molecular heterogeneity of tumors, and the lack of effective treatment. Thus, efforts are directed to better understand this neoplasia, its origin, development and, particularly the identification and validation of biomarkers for early detection of the disease in asymptomatic stage. In the present work, we confirmed by MRM method in individual ovarian tumor fluid samples the regulation of 27 proteins out of 33 identified in a highthroughput study. We speculate that the presence and/or differential abundance observed in tumor fluid is a cooperation primarily of high rates of secretion of such tumor proteins to extra tumor environment that will at the end accumulate in plasma, and also the accumulation of acute-phase proteins throughout the entire body. On top of that, consideration of physiological influences in the interpretation of expression observed, including age, menopause status, route-of-elimination kinetics and metabolism of the tumor marker, coexisting disease, hormonal imbalances, life-style influences (smoking, alcoholism, obesity), among others, are mandatory to enable the selection of good protein tumor marker candidates for extensive validation.

Supervised physical therapy in women treated with radiotherapy for breast cancer / Fisioterapia supervisionada nas mulheres em radioterapia para o câncer de mama / Terapia física supervisada en mujeres tratadas con radioterapia debido a cáncer de mama

ABSTRACT Objective: to evaluate the effect of physical therapy on the range of motion of the shoulders and perimetry of the upper limbs in women treated with radiotherapy for breast cancer. Methods: a total of 35 participants were randomized into two groups, with 18 in the control group (CG) and 17 in the study group (SG). Both of the groups underwent three evaluations to assess the range of motion of the shoulders and perimetry of the upper limbs, and the study group underwent supervised physical therapy for the upper limbs. Results: the CG had deficits in external rotation in evaluations 1, 2, and 3, whereas the SG had deficits in flexion, abduction, and external rotation in evaluation 1. The deficit in abduction was recovered in evaluation 2, whereas the deficits in all movements were recovered in evaluation 3. No significant differences in perimetry were observed between the groups. Conclusion: the applied supervised physical therapy was effective in recovering the deficit in abduction after radiotherapy, and the deficits in flexion and external rotation were recovered within two months after the end of radiotherapy. Registration number of the clinical trial: NCT02198118.

RESUMO Objetivo: avaliar o efeito da fisioterapia na amplitude de movimento do ombro e na perimetria do membro superior, aplicada durante o período da radioterapia nas mulheres em tratamento para o câncer de mama. Métodos: 35 voluntárias foram randomizadas em dois grupos, 18 para o grupo controle e 17 para o grupo de estudo. Os dois grupos foram submetidos a três avaliações da amplitude de movimento do ombro e perimetria do membro superior, sendo o grupo de estudo também submetido à fisioterapia supervisionada para os membros superiores. Resultados: o grupo controle apresentou déficit entre os membros para o movimento de rotação externa nas avaliações 1, 2 e 3. O grupo de estudo apresentou déficit entre os membros para os movimentos de flexão, abdução e rotação externa na avaliação 1. Houve recuperação do déficit de movimento de abdução na avaliação 2 e, na avaliação 3, os déficits de todos os movimentos estavam recuperados. Na análise da perimetria não foi observada diferença significativa. Conclusão: o protocolo fisioterapêutico supervisionado aplicado foi efetivo na recuperação do déficit de abdução pós-radioterapia e de flexão e rotação externa quando avaliados até 2 meses após o término da radioterapia. Número do registro do ensaio clínico: NCT02198118.

RESUMEN Objetivo: evaluar el efecto de la terapia física en el rango de movimiento de los hombros y la perimetría de las extremidades superiores en mujeres tratadas con radioterapia debido a cáncer de mama. Métodos: un total de 35 participantes fueron aleatorizadas en dos grupos, 18 en el grupo control y 17 en el grupo de estudio. Ambos grupos fueron sometidos a tres evaluaciones para evaluar el rango de movimiento de los hombros y la perimetría de las extremidades superiores, y el grupo de estudio fue sometido a terapia física supervisada de las extremidades superiores. Resultados: el grupo de control tuvo déficits en la rotación externa en la evaluación 1, 2, y 3, mientras que el grupo de estudio tuvo déficits en la flexión, abducción y rotación externa en la evaluación 1. El déficit en la abducción fue recuperado en la evaluación 2, mientras que los déficits en todos los movimientos fueron recuperados en la evaluación 3. No se observaron diferencias significativas en la perimetría. Conclusión: la terapia física supervisada aplicada fue efectiva en la recuperación del déficit en la abducción después de la radioterapia y los déficits en flexión y rotación externa fueron recuperados dos meses después de terminada la radioterapia. Número de registro del ensayo clínico: NCT02198118.

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.

Associação entre câncer de mama e doença periodontal / Association between breast cancer and periodontal disease

A doença periodontal (DP) é uma patologia inflamatória comumente relacionada à perda dental, na qual, em resposta à microbiota subgengival, o hospedeiro libera uma série de mediadores inflamatórios e enzimas que levam à degradação dos tecidos periodontais. Atualmente, tem sido sugerido que a inflamação associada ao câncer é similar àquela vista em inflamações crônicas. As células inflamatórias são recrutadas para dentro dos processos neoplásicos e liberam fatores que podem atuar na supressão do tumor por estímulo da resposta imune antitumoral ou, sob certas condições, parecem estimular o desenvolvimento do câncer. A ideia de que a resposta imunoinflamatória é o fator-chave que poderia explicar uma possível associação entre DP e câncer tem levado a comunidade científica a investigar quais os possíveis mecanismos envolvidos nessa relação. Diante disso, o objetivo deste trabalho foi analisar, na literatura científica, evidências da associação entre câncer de mama e DP, utilizando as bases de dados Pubmed, Cochrane, Lilacs e SciELO, abrangendo estudos publicados na última década.

ABCG2 is a potential marker of tumor-initiating cells in breast cancer.

The existence of tumor-initiating cells (TICs) within solid tumors has been hypothesized to explain tumor heterogeneity and resistance to cancer therapy. In breast cancer, the expression of CD44 and CD24 and the activity of aldehyde dehydrogenase 1 (ALDH1) can be used to selectively isolate a cell population enriched in TICs. However, the ideal marker to identify TICs has not been established. The aim of this study was to evaluate the expression of novel potential markers for TIC in breast carcinoma. We prospectively analyzed the expression of CD44, CD24, ABCG2, and CXCR4, and the activity of ALDH1 by using flow cytometry in 48 invasive ductal carcinomas from locally advanced and metastatic breast cancer patients who were administered primary chemotherapy. A mammosphere assay was employed in 30 samples. The relationship among flow cytometric analyses, ABCG2 gene expression, and clinical and pathological responses to therapy was analyzed. The GSE32646 database was analyzed in silico to identify genes associated with tumors with low and high ABCG2 expression. We observed that the presence of ABCG2(+) cells within the primary tumor was the only marker to predict the formation of mammospheres in vitro (R (2) = 0.15, p = 0.029). Quantitative polymerase chain reaction (qPCR) revealed a positive correlation between ABCG2 expression and the presence of ABCG2(+) cells within the primary tumor. The expression of ABCG2 was predictive of the response to neoadjuvant chemotherapy in our experiments and in the GSE32646 dataset (p = 0.04 and p = 0.002, respectively). The in silico analysis demonstrated that ABCG2(Up) breast cancer samples have a slower cell cycle and a higher expression of membrane proteins but a greater potential for chromosomal instability, metastasis, immune evasion, and resistance to hypoxia. Such genetic characteristics are compatible with highly aggressive and resistant tumors. Our results support the hypothesis that the presence of ABCG2(+) cells in breast carcinomas is a marker of resistance to chemotherapy, and based on in vitro assays and the genetic profile, we show, for the first time, that ABCG2 protein can be used as an independent marker for TIC identification in breast cancer.

Oral health after breast cancer treatment in postmenopausal women.

OBJECTIVE: Oral health can affect a patient's general health and quality of life. Given the increase in breast cancer survival rates, investigations of factors influencing the quality of life of survivors have gained importance. Therefore, the objective of our study was to characterize oral health in postmenopausal breast cancer survivors. METHODS: We conducted a matched case-control study. Forty-eight women who survived breast cancer (age 62.1±9.1 years) and 48 healthy controls (age 61.8±8.6 years) were included. For each case and control, a complete oral evaluation chart was completed. RESULTS: The prevalence of chronic periodontal disease was 98% in breast cancer survivors and 87% in controls. The breast cancer survivors had a median of 16 remaining teeth, whereas controls had a median of 22 remaining teeth (p = 0.03). The percentage of sites with gingival bleeding was 16.05% (0-100%) in breast cancer survivors and 0% (0-72%) in controls (p = 0.04). CONCLUSION: Chronic periodontal disease and tooth loss were highly prevalent in postmenopausal breast cancer survivors. To improve survivors' quality of life, a preventive oral health evaluation should be available prior to cancer treatment.

Avaliação oncológica após reconstrução mamária com lipoenxertia / Oncologic evaluation after breast reconstruction with fat grafting

Introdução: A reconstrução mamária é etapa fundamental no tratamento de pacientes com câncer de mama, sendo a lipoenxertia um importante recurso para melhora no resultado estético. Todavia, recentemente, alguns autores têm questionado a segurança da lipoenxertia, sugerindo que essa técnica possa aumentar o risco de recidiva tumoral local. Métodos: Estudo retrospectivo, tipo coorte transversal, realizado por meio de revisão de prontuários médicos de pacientes submetidas a reconstrução mamária com lipoenxertia pela Divisão de Cirurgia Plástica do Hospital das Clínicas da FMRP-USP, no período de 2006 a 2010. Resultados: Foram selecionadas 18 pacientes, sendo que oito (44%) apresentaram tumor do tipo histológico ductal. Três pacientes (17%) foram submetidas a quimioterapia neoadjuvante, sendo que destas, duas (11%) foram submetidas também a quimioterapia adjuvante; nove (50%) foram submetidas apenas a quimioterapia adjuvante. Onze pacientes (61%) foram submetidas a radioterapia adjuvante, e treze (72%) fizeram tratamento hormonal. Quanto à reconstrução da mama, oito pacientes (44,4%) realizaram TRAM, seis (33,3%), expansor mais prótese e quatro (22,2%), grande dorsal mais prótese. O número de sessões de lipoenxertia variou entre um e quatro. Não foi identificado nenhum caso de recidiva tumoral locorregional. Conclusão: Não foi evidenciado nenhum caso de recidiva tumoral locorregional, o que acrescenta, até o momento, confiabilidade e segurança à lipoenxertia como arsenal para os procedimentos que visam melhorar os resultados da reconstrução mamária após o tratamento oncológico.

Introduction: Breast reconstruction is an essential step in the treatment of patients with breast cancer. Fat grafting is an important resource for improved esthetic results. Recently, however, some authors have questioned the safety of fat grafting, suggestoncolóing that this technique can increase the risk of local tumor recurrence. Methods: A retrospective, cross-sectional cohort study was conducted through a review of medical records of patients who underwent breast reconstruction with fat grafting by the Plastic Surgery Division of the Clinical Hospital of the Ribeirão Preto Faculty of Medicine of the University of São Paulo (FMRP-USP), from 2006 to 2010. Results: We selected 18 patients, of whom eight (44%) had ductal carcinoma by histology. Three patients (17%) underwent neoadjuvant chemotherapy, and of these, two (11%) were also subjected to adjuvant chemotherapy. Nine (50%) received only adjuvant chemotherapy. Eleven patients (61%) underwent adjuvant radiotherapy, and thirteen (72%) had hormonal therapy. For breast reconstruction, eight patients (44.4%) underwent a transverse rectus abdominis myocutaneous (TRAM) flap procedure, six (33.3%) had an expander and prostheses, and four (22.2%) underwent a procedure with the latissimus dorsi muscle flap and prostheses. The number of fat grafting sessions ranged from one to four. No cases of locoregional recurrence of breast cancer were identified. Conclusion: There has been no evidence of locoregional recurrence to date, demonstrating that fat grafting is a reliable and safe procedure for improving the results of breast reconstruction after cancer treatment.

Expression of the Classical and Nonclassical HLA Molecules in Breast Cancer.

Considering that downregulation of HLA expression could represent a potential mechanism for breast carcinogenesis and metastasis, the aim of the present study was to use immunohistochemical methods to analyze the expression of HLA-Ia, HLA-DR, HLA-DQ, HLA-E, and HLA-G in invasive ductal carcinoma (IDC) of the breast and to relate this HLA profile to anatomopathological parameters. Fifty-two IDC from breast biopsies were stratified according to histological differentiation (well, moderately, and poorly differentiated) and to the presence of metastases in axillary lymph nodes. The expression of HLA molecules was assessed by immunohistochemistry, using a computer-assisted system. Overall, 31 (59.6%) out of the 52 IDC breast biopsies exhibited high expression of HLA-G, but only 14 (26.9%) showed high expression of HLA-E. A large number (41, 78.8%) of the biopsies showed low expression of HLA-Ia, while 45 (86.5%) showed high expression of HLA-DQ and 36 (69.2%) underexpressed HLA-DR. Moreover, 24 (41.2%) of 52 biopsies had both low HLA-Ia expression and high HLA-G expression, while 11 (21.2%) had low HLA-Ia expression and high HLA-E expression. These results suggest that, by different mechanisms, the downregulation of HLA-Ia, HLA-E, and HLA-DR and the upregulation of HLA-G and HLA-DQ are associated with immune response evasion and breast cancer aggressiveness.

Tumor neuroendócrino primário de mama: relato de três casos e revisão de literatura / Primary neuroendocrine carcinoma of the breast: case report and literature review

Os tumores neuroendócrinos primários de mama (TNPMs) são incomuns e não há consenso quanto a tratamento e prognóstico. No presente trabalho, foram revisados os diagnósticos de 1.184 pacientes com câncer de mama atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP/USP), identificando três casos que preenchiam os critérios de TNPM, segundo classificação estabelecida pela Organização Mundial da Saúde (OMS) em 2003. Foram avaliados os achados clinicopatológicos e imuno-histoquímicos e as terapias realizadas, buscando caracterizar os padrões histopatológicos e de comportamento distintos dos carcinomas convencionais de mama.

Primary neuroendocrine breast carcinomas (NECs) are uncommon. Moreover, there is no consensus as to its treatment and prognosis. In this study, the diagnoses of 1,184 cases of breast cancer treated at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto/Universidade de São Paulo (HCFMRP/USP) were reviewed. Three among them fulfilled the criteria for primary NEC according to the classification established by the World Health Organization (WHO) in 2003. Clinicopathological, immunohistochemical features and treatments were assessed in order to characterize histopathological and distinct patterns of conventional breast carcinomas.

CD44+/CD24- cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast.

The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), anti-human CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumor-initiating cells in stage I and II breast cancer.

Linfedema pós-câncer de mama: comparação de duas técnicas fisioterapêuticas - estudo piloto / Lymphedema after breast cancer: comparison between two physical therapy techniques - a pilot study

INTRODUÇÃO: O câncer de mama apresenta relevantes efeitos físicos e psicológicos. Entre as formas de tratamento, as cirurgias conservadoras, muitas vezes com esvaziamento linfático axilar e seguidas por radioterapia, têm papel preponderante. Uma importante complicação pós-tratamento é o surgimento do linfedema no membro superior homolateral. A principal terapêutica para o linfedema é a fisioterapia complexa descongestiva. A estimulação elétrica vem sendo utilizada na prática clínica para a redução do edema, sendo, por isso, uma nova alternativa para o tratamento do linfedema a ser pesquisada. OBJETIVO: Realizar um estudo piloto para comparar os efeitos da fisioterapia complexa descongestiva com um protocolo que inclui estimulação elétrica, exercícios terapêuticos e uso da braçadeira elástica na redução do linfedema secundário com o esvaziamento linfático axilar. MATERIAIS E MÉTODOS: Doze voluntárias foram divididas aleatoriamente em dois grupos e submetidas a diferentes protocolos terapêuticos (FCD e EAV). A redução do linfedema foi avaliada por meio da perimetria e da volumetria de ambos os membros superiores. As intervenções foram realizadas duas vezes por semana por um período de sete semanas. RESULTADOS: Não se observou diferença na redução do linfedema entre os protocolos utilizados. CONCLUSÃO: Com uma amostra pequena de pacientes, não se observaram diferenças entre as técnicas na redução do linfedema quando aplicadas na fase de manutenção. Fatores como tempo de instalação do linfedema, grau de esvaziamento axilar, radicalidade da cirurgia e aplicação de radioterapia na região afetada contribuem para o estágio do linfedema e sucesso de seu tratamento.

INTRODUCTION: Breast cancer is an illness with physical and psychological important effects. Its treatment forms include axillary dissection sugery. A considerable postoperative consequence is the upper limb lymphedema. The principal therapy of lymphedema is descongestive lymphatic therapy. Electrical stimulation has been applied clinically in reduction of edema. Due to this, it is a new alternative for lymphedema treatment to be studied. OBJECTIVE: To compare the descongestive lymphatic therapy with a protocol that includes electrical stimulation, upper limb exercises and compression by bandages in the reduction of axillary dissection secondary lymphedema. METHOD: twelve volunteers were distributed randomly in the two groups and they were submitted to different treatments (FCD and EAV). The reduction of lymphedema was valued by perimetry and volumetry of upper limb. The interventions were realized twice a week during a period of seven weeks. RESULTS: It did not reach statistic significance in reduction of edema. CONCLUSION: With a small sample of patients, there was no difference between the techniques in reducing lymphedema when applied to the maintenance phase. The time of installation of lymphedema, axillary dissection, sugery and radiotherapy contribute for degree of lymphedema and its treatment. The use of bandages compressive by the patients influences the success of therapy.

Variability in estrogen-metabolizing genes and their association with genomic instability in untreated breast cancer patients and healthy women.

In the present study, we investigated the relationship between polymorphisms in the estrogen-metabolizing genes CYP17, CYP1B1, CYP1A1, and COMT and genomic instability in the peripheral blood lymphocytes of 62 BC patients and 62 controls considering that increased or prolonged exposure to estrogen can damage the DNA molecule and increase the genomic instability process in breast tissue. Our data demonstrated increased genomic instability in BC patients and that individuals with higher frequencies of MN exhibited higher risk to BC when belonging Val/Met genotype of the COMT gene. We also observed that CYP17 and CYP1A1 polymorphisms can modify the risk to BC depending on the menopause status. We can conclude that the genetic background in estrogen metabolism pathway can modulate chromosome damage in healthy controls and patients and thereby influence the risk to BC. These findings suggest the importance to ally biomarkers of susceptibility and effects to estimate risk groups.