Association between SNP rs527616 in lncRNA AQP4-AS1 and susceptibility to breast cancer in a southern Brazilian population.

Breast cancer (BC) is the leading cause of death by this disease in women worldwide. Among the factors involved in tumorigenesis, long non-coding RNAs (lncRNAs) and their differential expression have been associated. Differences in gene expression may be triggered by variations in DNA sequence, including single nucleotide polymorphisms (SNPs). In the present study, we analyzed the rs527616 (C>G), located in the lncRNA AQP4-AS1, using PCR-SSP in 306 BC patients and 312 controls, from a Brazilian population. In the BC group, the frequency found for CG heterozygotes was above the expected and the overdominant model is the best one to explain our results (OR: 1.70, IC 95%: 1.23-2.34, P<0.001). Furthermore, the SNP were associated with age at BC diagnosis and the risk genotype more frequent in the older age group. According to TCGA data, AQP4-AS1 is down-regulated in BC tissue, and the overexpression is associated with better prognoses, including Luminal A, HER2-, stage 1 of disease and smaller tumor. In conclusion, the CG genotype is associated with increased susceptibility in the southern Brazilian population. This SNP is mapped in the lncRNA AQP4-AS1, showing differential expression in BC samples. Based on these results, we emphasize the potential of the role of AQP4-AS1 in cancer.

Integrated analysis of label-free quantitative proteomics and bioinformatics reveal insights into signaling pathways in male breast cancer.

Male breast cancer (MBC) is a rare malignancy that accounts for about 1.8% of all breast cancer cases. In contrast to the high number of the "omics" studies in breast cancer in women, only recently molecular approaches have been performed in MBC research. High-throughput proteomics based methodologies are promisor strategies to characterize the MBC proteomic signatures and their association with clinico-pathological parameters. In this study, the label-free quantification-mass spectrometry and bioinformatics approaches were applied to analyze the proteomic profiling of a MBC case using the primary breast tumor and the corresponding axillary metastatic lymph nodes and adjacent non-tumor breast tissues. The differentially expressed proteins were identified in the signaling pathways of granzyme B, sirtuins, eIF2, actin cytoskeleton, eNOS, acute phase response and calcium and were connected to the upstream regulators MYC, PI3K SMARCA4 and cancer-related chemical drugs. An additional proteomic comparative analysis was performed with a primary breast tumor of a female patient and revealed an interesting set of proteins, which were mainly involved in cancer biology. Together, our data provide a relevant data source for the MBC research that can help the therapeutic strategies for its management.

A genetic variant in microRNA-146a is associated with sporadic breast cancer in a Southern Brazilian Population.

MicroRNAs (miRNAs) play an essential role in gene expression and affect the development of tumours, including breast cancer (BC). Polymorphisms in miRNA genes can affect the interaction of miRNAs with their target messenger RNA by interfering, creating or disrupting target sites. The single nucleotide polymorphism (SNP) rs2910164, located in the seed region of miR146a, was shown to be associated with BC among different populations. In the present study, we investigated whether rs2910164 is associated with BC in 326 patients and 411 controls from a Brazilian population of predominantly European ancestry. The presence of the allele rs2910164*C was associated with an increased risk of BC (OR=1.4, 95% CI=1.03-1.85, p = 0.03). We also analysed publicly available RNA-seq data to evaluate if miR146a is differentially expressed in different subtypes of BC. Genotyping was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP). By leveraging public data from TCGA database, we analysed 461 patients and found that miR146a is significantly more expressed in BC than in non-tumor tissue (1.47 fold, p = 0.02) and is expressed to a greater degree in aggressive BC subtypes.

Nonprocessed adipose tissue graft in the treatment of peri-implant osseous defects in the rabbit's tibiae: a pilot study.

We hypothesized that a new technique using nonprocessed adipose tissue could regenerate bone around dental implants. Eighteen rabbits received 1 implant per tibia surrounded by a surgically created osseous defect. The defects were assigned for treatment into 3 groups: C, AT, and AB. The percentages of bone-to-implant contact were 17.64% ± 16.22% (AB), 3.54% ± 7.08% (AT), and 12.71% ± 10.11% (C) (ρ = 0.25). The use of adipose tissue around surgically created peri-implant osseous defects interferes with bone formation.

Training in oncoplastic surgery for mastologists.

OBJECTIVE: The radical change in the treatment of breast cancer has promoted the necessity for more comprehensive training of the professionals involved, ensuring the preservation of oncological safety while also allowing for cosmetic interventions to benefit breast cancer survivors. The aim of this study was to present the methods employed in the training of breast surgeons, highlighting the importance of oncoplasty and breast reconstruction. METHODS: A literature review was conducted in two databases, identifying articles related to medical education in the context of oncoplastic surgery and breast reconstruction. We also assessed the Brazilian experience in oncoplastic centers. RESULTS: The basis for educational discussions was derived from 16 articles. We observed approaches that included hands-on courses utilizing simulator models, porcine models, cadaver labs, and fellowship programs. Positive outcomes were observed in Brazil, a fact based on seven oncoplasty training centers for senior mastologists and five training centers for junior mastologists. From 2009 to 2023, an estimated 452 seniors and 42 juniors received training, representing approximately 30% of mastologists in Brazil who have acquired training and experience in oncoplasty. CONCLUSION: Despite the limited number of publications on training methods, oncoplastic centers have made significant progress in Brazil, establishing a successful model that can be replicated in other countries.

Fragmented adipose tissue graft for bone healing: histological and histometric study in rabbits' calvaria.

OBJECTIVE: The adipose tissue represents an important reservoir of stem cells. There are few studies in the literature with which to histologically evaluate whether or not the adipose tissue graft is really a safe option to achieve bone repair. This study histologically analyzed the effect of fragmented autogenous adipose tissue grafts on bone healing in surgically created, critical-size defects (CSD) in a rabbit's calvaria. STUDY DESIGN: Forty-two New Zealand rabbits were used in this study. CSD that were 15 mm in diameter were created in the calvarium of each animal. The defects were randomly divided into two groups: in Group C (control), the defect was filled only by a blood clot and, in Group FAT (i.e., fragmented adipose tissue), the defect was filled with fragmented autogenous adipose tissue grafts. The groups were divided into subgroups (n = 7) for euthanasia at 7, 15, and 40 days after the procedure had been conducted. Histologic and histometric analyses were performed. Data were statistically analysed with ANOVA and Tukey's tests (p < 0.05). RESULTS: The amount of bone formation did not show statistically significant differences seven days after the operation, which indicates that the groups had similar amounts of mineral deposition in the earlier period of the repair. Conversely, a significant of amount of bone matrix deposition was identified in the FAT group at 15 and 40 days following the operation, both on the border and in the body of the defect. Such an outcome was not found in the control group. CONCLUSION: In this study, an autologous adipose tissue graft may be considered as likely biomaterial for bone regeneration, since it positively affected the amount of bone formation in surgically created CSD in the rabbits' calvaria 40 days after the procedure had been performed. Further investigations with a longer time evaluation are warranted to determine the effectiveness of autologous adipose tissue graft in the bone healing.

Oncological safety of nipple-sparing mastectomy after neoadjuvant chemotherapy: a systematic review.

BACKGROUND: the use of nipple-sparing mastectomy (NSM) in local advanced breast cancer after neoadjuvant chemotherapy (NQT) is increasing, despite few studies on the subject. The aim of this systematic review was to determine the safety of NSM after neoadjuvant chemotherapy. METHODS: for this systematic review we searched MEDLINE; Cochrane; Scientific Electronic Library Online (SciELO); Embase and Scopus. A literature search of all original studies including randomized controlled trials, cohort studies and case-control studies comparing women undergoing NSM after neoadjuvant chemotherapy for breast cancer was undertaken. Outcomes were locoregional recurrence (LRR), nipple recurrence and distant recurrence (DR). Data analysis was undertaken to explore the safety of NSM after NQT. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021276778. FINDINGS: a total of 437 articles were identified. Four articles were included with 1466 patients all of which had a high to serious risk of overall bias. Local recurrence in the NSM after the NQT group ranged from zero to 9.8%. Nippleareolar complex (NAC) recurrence ranged from zero to 2.1%. The distant recurrence rate ranged from 6.5% to 16%. Due to the lack of pattern among the control groups, it was not possible to perform a meta-analysis. INTERPRETATION: this review provides information for decision making in performing NSM after NQT. Despite the low rates of local recurrence and patients should be counseled about limited oncological information.

Comprehensive analysis of the large and small ribosomal proteins in breast cancer: Insights on proteomic and transcriptomic expression patterns, regulation, mutational landscape, and prognostic significance.

Several evidence has demonstrated the involvement of the ribosomal proteins (RPs) in many malignancies, however, the function and clinical relevance of the RPs in breast cancer remains unclear. The present study aims to contribute to the understanding of the role of the RPs in breast tumorigenesis and its clinical implications in the field of biomarker discovery and outcome prediction. We investigated the proteomic and transcriptomic expression of the RPs in non-tumor and tumor tissues of different breast cancer subtypes, and integrated bioinformatics approaches and online databases to comprehensively evaluate the potential functions, regulatory networks, mutational landscape, and prognostic values of the ribosomal proteins in breast cancer. Our results show that 33 RPs have deregulated expression in breast cancer and its subtypes and that 26 RPs have potential as prognostic markers in a subtype-dependent way, with mutations in RP genes being frequent in breast tumors and related to overall survival and relapse-free status. Our RP gene regulatory network indicates the transcription factors MYC, ETS1, and SPI1, and the miRNAs has-let-7c-5p, has-mir-20b-5p, and has-mir-4668-3p as regulators of the RPs expression in breast cancer. The RPs were associated with several clinicopathological parameters of breast cancer and predicted to be involved in ribosomal-independent mechanisms such as regulation of the SLITS-ROBO pathway. This study comprehensively investigated the ribosomal proteins in breast cancer, suggesting that the RPs have clinical potential as biomarkers of diagnostic and prognostic, also providing an in-depth view of the RPs significance in breast cancer.

Exposed Implant after Immediate Breast Reconstruction - Presentation and Analysis of a Clinical Management Protocol.

OBJECTIVE: Infection and exposure of the implant are some of the most common and concerning complications after implant-based breast reconstruction. Currently, there is no consensus on the management of these complications. The aim of the present study was to review our cases and to present a clinical protocol. METHODS: We conducted a retrospective review of consecutive patients submitted to implant-based breast reconstruction between 2014 and 2016. All patients were managed according to a specific and structured protocol. RESULTS: Implant exposure occurred in 33 out of 277 (11.9%) implant-based reconstructions. Among these, two patients had history of radiotherapy and had their implant removed; Delayed reconstruction with a myocutaneous flap was performed in both cases. Signs of severe local infection were observed in 12 patients, and another 5 presented with extensive tissue necrosis, and they were all submitted to implant removal; of them, 8 underwent reconstruction with a tissue expander, and 2, with a myocutaneous flap. The remaining 14 patients had no signs of severe infection, previous irradiation or extensive tissue necrosis, and were submitted to primary suture as an attempt to salvage the implant. Of these, 8 cases (57.1%) managed to keep the original implant. CONCLUSION: Our clinical protocol is based on three key points: history of radiotherapy, severe infection, and extensive tissue necrosis. It is a practical and potentially-reproducible method of managing one of the most common complications of implant-based breast reconstruction.

OBJECTIVO: Infecção e exposição da prótese são algumas das complicações mais comuns e preocupantes após reconstrução da mama com implantes. Atualmente, ainda não há consenso quanto ao manejo destas complicações. O objetivo deste estudo foi o de revisar os casos da nossa instituição e apresentar um protocolo clínico. MéTODOS: Realizou-se uma revisão retrospectiva de todos os casos consecutivos submetidos a reconstrução mamária imediata com prótese entre 2014 e 2016. Todos os casos foram conduzidos de acordo com um protocolo específico e estruturado. RESULTADOS: A exposição do implante ocorreu em 33 de 227 reconstruções (11,9%). Dentre estas, duas pacientes tinham histórico de radioterapia, e foram submetidas a remoção da prótese e posterior reconstrução com retalho miocutâneo. Sinais de infecção local grave foram observados em 12 pacientes, e, em 5, necrose extensa de tecido, e todas foram submetidas a remoção dos implantes; destas, 8 foram reconstruídas com expansor, e 2, com retalho miocutâneo. As 14 pacientes remanecentes não haviam sido submetidas previamente à radioterapia, não tinham sinais de infecção, nem necrose extensa; portanto, foram submetidas a sutura primária em uma tentativa de salvar a prótese. Dessas, 8 pacientes (57,1%) conseguiram manter os implantes originais. CONCLUSãO: Nosso protocolo clínico é baseado em três pontos principais: histórico de radioterapia, infecção grave, e necrose extensa de tecido. Ele constitui um método prático e potencialmente reprodutível de manejo de uma das complicações mais comuns da reconstrução mamária com implantes.

Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients.

MicroRNAs derived from extracellular vesicles (EV-miRNAs) are circulating miRNAs considered as potential new diagnostic markers for cancer that can be easily detected in liquid biopsies. In this study, we performed RNA sequencing analysis as a screening strategy to identify EV-miRNAs derived from serum of clinically well-annotated breast cancer (BC) patients from the south of Brazil. EVs from three groups of samples (healthy controls (CT), luminal A (LA), and triple-negative (TNBC)) were isolated from serum using a precipitation method and analyzed by RNA-seq (screening phase). Subsequently, four EV-miRNAs (miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p) were selected to be quantified by quantitative real-time PCR (RT-qPCR) in individual samples (test phase). A panel composed of miR-142-5p, miR-320a, and miR-4433b-5p distinguished BC patients from CT with an area under the curve (AUC) of 0.8387 (93.33% sensitivity, 68.75% specificity). The combination of miR-142-5p and miR-320a distinguished LA patients from CT with an AUC of 0.9410 (100% sensitivity, 93.80% specificity). Interestingly, decreased expression of miR-142-5p and miR-150-5p were significantly associated with more advanced tumor grades (grade III), while the decreased expression of miR-142-5p and miR-320a was associated with a larger tumor size. These results provide insights into the potential application of EVs-miRNAs from serum as novel specific markers for early diagnosis of BC.

Training in oncoplastic surgery for mastologists

SUMMARY OBJECTIVE: The radical change in the treatment of breast cancer has promoted the necessity for more comprehensive training of the professionals involved, ensuring the preservation of oncological safety while also allowing for cosmetic interventions to benefit breast cancer survivors. The aim of this study was to present the methods employed in the training of breast surgeons, highlighting the importance of oncoplasty and breast reconstruction. METHODS: A literature review was conducted in two databases, identifying articles related to medical education in the context of oncoplastic surgery and breast reconstruction. We also assessed the Brazilian experience in oncoplastic centers. RESULTS: The basis for educational discussions was derived from 16 articles. We observed approaches that included hands-on courses utilizing simulator models, porcine models, cadaver labs, and fellowship programs. Positive outcomes were observed in Brazil, a fact based on seven oncoplasty training centers for senior mastologists and five training centers for junior mastologists. From 2009 to 2023, an estimated 452 seniors and 42 juniors received training, representing approximately 30% of mastologists in Brazil who have acquired training and experience in oncoplasty. CONCLUSION: Despite the limited number of publications on training methods, oncoplastic centers have made significant progress in Brazil, establishing a successful model that can be replicated in other countries.

High-throughput mass spectrometry and bioinformatics analysis of breast cancer proteomic data.

Data present here describe a comparative proteomic analysis among the malignant [primary breast tumor (PT) and axillary metastatic lymph nodes (LN)], and the non-tumor [contralateral (NCT) and adjacent (ANT)] breast tissues. Protein identification and quantification were performed through label-free mass spectrometry using a nano-liquid chromatography coupled to an electrospray ionization-mass spectrometry (nLC-ESI-MS/MS). The mass spectrometry proteomic data have been deposited to the ProteomeXchange Consortium via PRIDE partner repository with the dataset identifier PXD012431. A total of 462 differentially expressed proteins was identified among these tissues and was analyzed in six groups' comparisons (named NCTxANT, PTxNCT, PTxANT, LNxNCT, LNxANT and PTxLN). Proteins at 1.5 log2 fold change were submitted to the Ingenuity® Pathway Analysis (IPA) software version 2.3 (QIAGEN Inc.) to identify biological pathways, disease and function annotation, and interaction networks related to cancer biology. The detailed data present here provides information about the proteome alterations and their role on breast tumorigenesis. This information can lead to novel biological insights on cancer research. For further interpretation of these data, please see our research article 'Quantitative label-free mass spectrometry using contralateral and adjacent breast tissues reveal differentially expressed proteins and their predicted impacts on pathways and cellular functions in breast cancer' [2].

Oncological safety of nipple-sparing mastectomy after neoadjuvant chemotherapy: a systematic review / Segurança oncológica da mastectomia conservadora do mamilo após quimioterapia neoadjuvante: revisão sistemática

ABSTRACT Background: the use of nipple-sparing mastectomy (NSM) in local advanced breast cancer after neoadjuvant chemotherapy (NQT) is increasing, despite few studies on the subject. The aim of this systematic review was to determine the safety of NSM after neoadjuvant chemotherapy. Methods: for this systematic review we searched MEDLINE; Cochrane; Scientific Electronic Library Online (SciELO); Embase and Scopus. A literature search of all original studies including randomized controlled trials, cohort studies and case-control studies comparing women undergoing NSM after neoadjuvant chemotherapy for breast cancer was undertaken. Outcomes were locoregional recurrence (LRR), nipple recurrence and distant recurrence (DR). Data analysis was undertaken to explore the safety of NSM after NQT. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021276778. Findings: a total of 437 articles were identified. Four articles were included with 1466 patients all of which had a high to serious risk of overall bias. Local recurrence in the NSM after the NQT group ranged from zero to 9.8%. Nippleareolar complex (NAC) recurrence ranged from zero to 2.1%. The distant recurrence rate ranged from 6.5% to 16%. Due to the lack of pattern among the control groups, it was not possible to perform a meta-analysis. Interpretation: this review provides information for decision making in performing NSM after NQT. Despite the low rates of local recurrence and patients should be counseled about limited oncological information.

RESUMO Introdução: O uso de mastectomia preservadora de complexo aréolo-papilar (MPCAP) no câncer de mama localmente avançado após quimioterapia neoadjuvante (QTN) é crescente, apesar de ainda haver poucos estudos abordando o assunto. O objetivo desta revisão sistemática foi determinar a segurança da MPCAP após a quimioterapia neoadjuvante. Métodos: para esta revisão sistemática, pesquisamos no MEDLINE; Cochrane; Scientific Electronic Library Online (SciELO); Embase e Scopus. Foi realizada uma busca na literatura de todos os estudos originais, incluindo ensaios clínicos randomizados, estudos de coorte e estudos de caso-controle comparando mulheres submetidas a MPCAP após quimioterapia neoadjuvante para câncer de mama. Os desfechos foram recorrência locorregional, recidiva em papila e recorrência à distância. A análise dos dados foi realizada para avaliar a segurança da mastectomia preservadora de complexo aréolo-papilar após o QTN. A qualidade da evidência foi avaliada com a ferramenta de avaliação de risco de viés da Cochrane - ROBINS-I. Este estudo está registrado no PROSPERO, número CRD42021276778. Resultados: Um total de 437 artigos foram identificados. Quatro artigos foram incluídos na análise, totalizando 1466 pacientes, todos com risco de viés geral moderado a alto. A recorrência local no grupo MPCAP após QTN variou de zero a 9,8%. A recorrência no complexo aréolo-papilar (CAP) variou de zero a 2,1%. A taxa de recorrência à distância variou de 6,5% a 16%. Devido à falta de padrão entre os grupos de controle, não foi possível realizar uma meta-análise. Interpretação: esta revisão fornece informações para a tomada de decisão na realização de NSM após QTN. Apesar das baixas taxas de recorrência local, os pacientes devem ser orientados sobre as informações oncológicas limitadas.

Cancer stem cell markers ALDH1 and CD44+/CD24- phenotype and their prognosis impact in invasive ductal carcinoma.

Breast cancer is a very heterogeneous disease. The intrinsic molecular subtypes can explain the intertumoral heterogeneity and the cancer stem cell (CSC) hypothesis can explain the intratumoral heterogeneity of this kind of tumor. CD44+/CD24- phenotype and ALDH1 expression are the major CSC markers described in invasive breast cancer. In the present study, 144 samples of invasive breast carcinoma, no special type were distributed in 15 tissue microarrays (TMA) and then evaluated for expression of the CD44+/CD24- phenotype and ALDH1 to understand the importance of these CSC markers and the clinical aspects of breast cancer. The samples were classified into four molecular subtypes according to clinicopathological criteria: Luminal A, Luminal B, HER2, and Basal-like. A statistical association was found between the molecular subtypes and the CSC markers, with HER2 the most frequent subtype for both markers. ALDH1 was also associated with other poor prognostic variables, such as a high histological grade and larger tumors, but it was not associated with the patients' prognosis in this sample and nor was the CD44+/CD24- phenotype in a multivariate analysis. There are still many controversies about the role of these markers in breast cancer molecular subtypes. The identification of these populations of cells, through immunohistochemical markers, can help to better understand the CSC theory in clinical practice and, in the near future, contribute to developing new target therapies.

A percepção e conduta sobre a medida da pressão arterial em pacientes com neoplasia de mama em cardiologistas e mastologistas / The perception and management of blood pressure measurement in patients with breast cancer in cardiologists and mastologistas

Embora pacientes submetidas ao tratamento cirúrgico para Neoplasia de Mama, de modo geral e frequente, recebam orientações para não medir a pressão arterial no braço homolateral ao seu tratamento, devemos reavaliar contemporaneamente e cientificamente estas recomendações. O propósito deste trabalho é demonstrar os dados de Medicina Baseada em Evidências e considerar a evolução da abordagem cirúrgica neste grupo de pacientes, atualizando estas recomendações e demostram dados de enquete sobre o assunto entre médicos de diferentes especialidades. Há suficiente suporte científico e explicações para que orientemos de forma individualizada e coerentemente estas pacientes em relação a medida da pressão arterial e consequentemente sua relação com o aparecimento do linfedema no braço homolateral, porém a Sociedade Brasileira de Cardiologia, pelo seu Departamento de Hipertensão Arterial não tem recomendações sobre este assunto. Que deve ser contextualizado devido a má percepção sobre o assunto, em repostas a uma enquete feita com Cardiologistas e Mastologistas sobre este tema (AU)

Although patients undergoing surgical treatment for breast cancer are often advised against measuring blood pressure in the arm on the same side as their treatment, it is crucial to reevaluate these recommendations using contemporary and scientific evidence. The objective of this study is to present empirical data on Evidence-Based Medicine and explore the evolving surgical approaches in this patient population. By updating these recommendations and showcasing survey results from physicians across different specialties, we aim to provide comprehensive guidance on the topic. While there is ample scientific support and explanations to individually and coherently guide these patients regarding blood pressure measurement and its potential association with lymphedema in the affected arm, it is important to note that the Brazilian Society of Cardiology, specifically its Department of Arterial Hypertension, does not currently offer recommendations on this matter. This contextualization is necessary due to the limited awareness and understanding of the subject, as revealed through responses obtained from Cardiologists and Mastologists participating in our survey.

Exposed Implant after Immediate Breast Reconstruction - Presentation and Analysis of a Clinical Management Protocol / Exposição de prótese após reconstrução imediata da mama: apresentação e análise de protocolo clínico

Abstract Objective Infection and exposure of the implant are some of the most common and concerning complications after implant-based breast reconstruction. Currently, there is no consensus on the management of these complications. The aim of the present study was to review our cases and to present a clinical protocol. Methods We conducted a retrospective review of consecutive patients submitted to implant-based breast reconstruction between 2014 and 2016. All patients were managed according to a specific and structured protocol. Results Implant exposure occurred in 33 out of 277 (11.9%) implant-based reconstructions. Among these, two patients had history of radiotherapy and had their implant removed; Delayed reconstruction with a myocutaneous flap was performed in both cases. Signs of severe local infection were observed in 12 patients, and another 5 presented with extensive tissue necrosis, and they were all submitted to implant removal; of them, 8 underwent reconstruction with a tissue expander, and 2, with a myocutaneous flap. The remaining 14 patients had no signs of severe infection, previous irradiation or extensive tissue necrosis, and were submitted to primary suture as an attempt to salvage the implant. Of these, 8 cases (57.1%) managed to keep the Conclusion Our clinical protocol is based on three key points: history of radiotherapy, severe infection, and extensive tissue necrosis. It is a practical and potentially-reproducible method of managing one of the most common complications of implant-based breast reconstruction.

Resumo Objectivo Infecção e exposição da prótese são algumas das complicações mais comuns e preocupantes após reconstrução da mama com implantes. Atualmente, ainda não há consenso quanto ao manejo destas complicações. O objetivo deste estudo foi o de revisar os casos da nossa instituição e apresentar um protocolo clínico. Métodos Realizou-se uma revisão retrospectiva de todos os casos consecutivos submetidos a reconstrução mamária imediata com prótese entre 2014 e 2016. Todos os casos foram conduzidos de acordo com um protocolo específico e estruturado. Resultados A exposição do implante ocorreu em 33 de 227 reconstruções (11,9%). Dentre estas, duas pacientes tinham histórico de radioterapia, e foram submetidas a remoção da prótese e posterior reconstrução com retalho miocutâneo. Sinais de infecção local grave foram observados em 12 pacientes, e, em 5, necrose extensa de tecido, e todas foram submetidas a remoção dos implantes; destas, 8 foram recons truídas com expansor, e 2, com retalho miocutâneo. As 14 pacientes remanecentes não haviam sido submetidas previamente à radioterapia, não tinham sinais de infecção, nem necrose extensa; portanto, foram submetidas a sutura primária em uma tentativa de salvar a prótese. Dessas, 8 pacientes (57,1%) conseguiram manter os implantes originais. Conclusão Nosso protocolo clínico é baseado em três pontos principais: histórico de radioterapia, infecção grave, e necrose extensa de tecido. Ele constitui um método prático e potencialmente reprodutível de manejo de uma das complicações mais comuns da reconstrução mamária com implantes.

Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines.

MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. The gene is located at 9p21, a chromosome region often deleted in breast carcinomas, similar to CDKN2A, a recognized tumor suppressor gene. Several research groups have shown that MTAP acts as a tumor suppressor, and some therapeutic approaches were proposed based on a tumors´ MTAP status. We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer. Cytotoxicity assays with inhibitors of de novo adenine synthesis (5-FU, AZA and MTX) after MTAP gene knockdown showed an increased sensitivity, mainly to 5-FU. MTAP expression was also evaluated in two groups of samples from breast cancer patients, fresh tumors and paired normal breast tissue, and from formalin-fixed paraffin embedded (FFPE) core breast cancer samples diagnosed as Luminal-A tumors and triple negative breast tumors (TNBC). The difference of MTAP expression between fresh tumors and normal tissues was not statistically significant. However, MTAP expression was significantly higher in Luminal-A breast tumors than in TNBC, suggesting the lack of expression in more aggressive breast tumors and the possibility of using the new approaches based on MTAP status in TNBC.

When to indicate radiotherapy after nipple-sparing mastectomy? Systematic review / Quando indicar radioterapia após mastectomia nipple-sparing? Revisão sistemática

Introduction: Nipple-sparing mastectomy (NSM) and preservation of the nipple-areola complex (NAC) represent a therapeutic option of breast cancer with a better aesthetic result, a positive impact on body image and more satisfaction than the reconstruction of the NAC. It is questioned the indication of radiotherapy when the NAC is maintained and its potential aesthetic impairment. Objective: To examine the indication of radiotherapy in NSM and, secondarily, the incidence of NAC involvement and local recurrence rates. Methods: Systematic review carried out in the PubMed database with the terms ("breast neoplasm" [Mesh] OR "breast cancer") AND ("radiotherapy" OR "radiation therapy") AND ("nipple sparing mastectomy" OR "mastectomies" OR "subcutaneous mastectomies"). The selection of the studies, the evaluation of its quality and data extraction were carried out independently by four reviewers. Results: The indications for radiotherapy after NSM were: positive axilla, tumors over 5 cm and retroareolar tissue remaining greater than 5 mm. The NAC involvement occurred in 5 to 26.1% in the definitive anatomopathological study. NAC recurrence occurred from 2.59 to 10%. NAC necrosis occurred in 2.2 to 43.4%. Conclusions: The radiotherapy indications for NSM seem to follow the same classical indications for radiotherapy after mastectomy. The relapse index in NAC was not shown to be larger and without difference for the type of radiotherapy used. Radiotherapy should be based on factors that suggest a high risk for NAC involvement

Introdução: A mastectomia nipple-sparing (MNS) e a conservação do complexo aréolo-papilar (CAP) representam uma manobra terapêutica do câncer de mama com melhor resultado estético, impacto positivo na imagem corporal e mais satisfação do que a reconstrução do CAP. Questiona-se a indicação de radioterapia quando da manutenção do CAP e seu potencial prejuízo estético. Objetivo: Examinar a indicação de radioterapia em MNS e, secundariamente, a incidência do envolvimento do CAP e as taxas de recorrência local. Métodos: Revisão sistemática realizada na base de dados do PubMed com os termos ("breast neoplasm" [Mesh] OR "breast cancer") AND ("radiotherapy" OR "radiation therapy") AND ("nipple sparing mastectomy" OR "mastectomies" OR "subcutaneous mastectomies"). A seleção dos estudos, a avaliação da qualidade do estudo e a extração de dados foram realizadas de forma independente por quatro revisores. Resultados: As indicações para radioterapia após MNS foram: axila positiva, tumores acima de 5 cm e tecido retroareolar remanescente maior que 5 mm. O envolvimento do CAP ocorreu em 5 a 26,1% no anatomopatológico definitivo. A recorrência no CAP ocorreu de 2,59 a 10%. A necrose do CAP ocorreu em 2,2 a 43,4%. Conclusão: As indicações de radioterapia para MNS parecem seguir as mesmas indicações clássicas para radioterapia após mastectomia. O índice de recidiva no CAP não mostrou ser maior com uso de radioterapia nem ter diferença quanto ao seu tipo. A decisão de realizar a radioterapia deve se basear em fatores que sugerem alto risco para envolvimento do CAP

MANAGEMENT OF COMPLICATIONS IN RECONSTRUCTIVE MAMMOPLASTIES WITH PROSTHESES: SYSTEMATIC REVIEW / Condutas em complicações de mastectomias reconstruídas com próteses: revisão sistemática

Objective: The aims of this study were to determine the main managements of surgical complications in reconstructive mammoplasties with prostheses through a systematic literature review, and to evaluate the effectiveness in preserving the reconstruction. The secondary objective was to analyze factors regarding prosthetic loss. Methods: We used the MedLine database through the following expressions: "breast cancer" or "breast neoplasm" or "breast and neoplasm" or "breast and cancer" and "implants complications" or "implants and complications". The reference period for these studies comprised January 2000 to July 2016. Results: Of the 856 articles found, seven were included to analyze the applied protocols. The rate of saved prostheses after stratification of complications and use of managements varied from 45 to 100%, depending on the degree of complication. Other 12 articles that evaluated the factors associated with prosthetic loss were secondarily chosen. Radiotherapy was considered the most frequent factor and was found in seven studies. The number of lost prostheses varied from 0.9 to 22.7% in such studies. Conclusion: There is still no agreement on how to manage complications of reconstructive mammoplasties with prostheses. The decision remains a challenge, and therefore surgeons need to know the possible conducts in order to establish the most appropriate treatment.

Objetivos: O objetivo principal deste estudo foi determinar, por meio de revisão sistemática da literatura, as principais condutas nas complicações cirúrgicas de mastectomias reconstruídas com próteses, bem como avaliar a eficácia em preservar a reconstrução. O objetivo secundário foi analisar fatores relacionados à perda da prótese. Métodos: Foi empregado o banco de dados do MedLine, utilizando as expressões: breast cancer, ou breast neoplasm ou breast and neoplasm ou breast and cancer e implants complications ou implants and complications. O período de referência desses estudos foi de janeiro de 2000 até julho de 2016. Resultados: Dos 856 artigos encontrados, 7 foram incluídos para análise dos protocolos de condutas aplicados. A taxa de próteses salvas após estratificação das complicações e aplicação das condutas variou de 45 a 100%, a depender do grau de complexidade. Foram selecionados, secundariamente, outros 12 artigos que avaliaram fatores associados à perda da prótese. A mais frequente foi a radioterapia com 7 estudos. O número de próteses perdidas variou entre 0,9 e 22,7% nesses estudos. Conclusão: Ainda não existe unanimidade no manejo das complicações de mastectomias reconstruídas com próteses. Portanto, a decisão permanece desafiadora e o cirurgião necessita conhecer as possíveis condutas para definir a mais apropriada.