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.

Resumo Objetivo: A cirurgia de mama é considerada uma cirurgia limpa; entretanto, as taxas de infecção variam entre 3 e 15%. O objetivo deste estudo foi investigar no intraoperatório a presença de microbiota autóctone na mama. Métodos: Pedaços de tecido mamário coletados de 49 pacientes submetidas à cirurgia eletiva da mama (reconstrutiva, diagnóstica ou oncológica) foram cultivados. Os pedaços de tecido mamário tinham aproximadamente 1 cm de diâmetro e foram removidos da área retroareolar e dos quadrantes medial e lateral. Cada pedaço de tecido foi incubado em caldo BHI (brain heart infusion) por 7 dias a 37 ° C, e nos casos em que o meio ficou turvo devido ao crescimento de microrganismos, as amostras foram colocadas em placas de Petri para cultivo e isolamento de cepas e para identificação de espécies usando um contador automatizado. Resultados: O crescimento do microrganismo foi observado nas amostras de 10 das 49 pacientes (20,4%) e em 11 dos 218 pedaços de tecido (5%). As espécies detectadas foram Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus epidermidis, Sphingomonas paucimobilis e Aeromonas salmonicida. Nenhum paciente com amostras positivas apresentou infecção clínica no pós-operatório. Conclusão: A presença dessas bactérias no tecido mamário em aproximadamente 20% das pacientes desta série sugere que a cirurgia mamária deve ser considerada uma fonte potencial de contaminação que pode ter implicações nas reações adversas aos implantes mamários e deve ser estudada em um futuro próximo por suas implicações oncológicas na etiologia do linfoma de células grandes associado ao implante de mama.

Abstract Objective: Breast surgery is considered a clean surgery; however, the rates of infection range between 3 and 15%. The objective of the present study was to intraoperatively investigate the presence of autochthonous microbiota in the breast. Methods: Pieces of breast tissue collected from 49 patients who underwent elective breast surgery (reconstructive, diagnostic, or oncologic) were cultured. The pieces of breast tissue were approximately 1 cm in diameter and were removed from the retroareolar area, medial quadrant, and lateral quadrant. Each piece of tissue was incubated in brain heart infusion (BHI) broth for 7 days at 37°C, and in cases in which the medium became turbid due to microorganism growth, the samples were placed in Petri dishes for culturing and isolating strains and for identifying species using an automated counter. Results: Microorganism growth was observed in the samples of 10 of the 49 patients (20.4%) and in 11 of the 218 pieces of tissue (5%). The detected species were Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus epidermidis, Sphingomonas paucimobilis, and Aeromonas salmonicida. No patient with positive samples had clinical infection postoperatively. Conclusion: The presence of these bacteria in breast tissue in approximately 20% of the patients in this series suggests that breast surgery should be considered a potential source of contamination that may have implications for adverse reactions to breast implants and should be studied in the near future for their oncological implications in breast implant-associated large-cell lymphoma etiology.

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.

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.

Abstract 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.

Abstract 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.

Abstract Breast cancer (BC) is a heterogeneous disease, and it is the leading cause of death among women. NORAD and HCG11 are highly similar lncRNAs that present binding sites for PUMILIO proteins. PUMILIO acts on hundreds of mRNA targets, contributing to the modulation of gene expression. We analyzed the expression levels of NORAD and HCG11 in the BC subtypes luminal A (LA) and basal-like (BL), and the regulatory networks associated with these lncRNAs. In the analysis of TCGA cohort (n=329) and Brazilian BC samples (n=44), NORAD was up-regulated in LA while HCG11 was up-regulated in BL subtype. An increased expression of NORAD is associated with reduced disease-free survival in basal-like patients (p = 0.002), which suggests that its prognostic value could be different in specific subtypes. The biological pathways observed for the HCG11 network are linked to the epithelial-to-mesenchymal transition; while NORAD associated pathways appear to be related to luminal epithelial cell transformation. NORAD and HCG11 regulons respectively present 36% and 21.5% of PUMILIO targets, which suggests that these lncRNAs act as a decoy for PUMILIO. These lncRNAs seem to work as players in the differentiation process that drives breast cells to acquire distinct phenotypes related to a specific BC subtype.

Abstract Copy number alterations (CNAs) are a frequent feature in human breast cancer, and one of the hallmarks of genomic instability. The FOSL1, GSTP1 and CCND1 genes are located at 11q13, a cytoband commonly affected by CNA in breast cancer, with relevant function in progression and invasion. Our main goal was to analyze CNAs of these genes and determine their association with breast cancer subtypes. Seventy-three cases of invasive breast tumors [52 Luminal, 7 HER2+ and 14 triple negative (TNBC) subtypes] were analyzed by TaqMan assays. CNAs were observed for all genes, with gains more frequently observed. Gains of the FOSL1 gene were observed in 71% of the cases. This gene was the only one with a statistically significant difference (p<0.001) among tumor subtypes, with increased copy number in TNBC compared to luminal and HER2+. No significant association of CNA and clinical and histopathological parameters from the patients was observed. Additional studies in larger breast cancer patient cohorts based on more refined molecular subtypes are necessary to confirm the observed association of FOSL1 gain with aggressive breast tumors phenotypes.

Abstract 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.

O linfonodo sentinela é o primeiro linfonodo que recebe a drenagem linfática proveniente do câncer de mama. A sua detecção tem a finalidade de predizer o estado da axila e evitar o esvaziamento axilar nos pacientes sem comprometimento metastático. Os autores realizaram uma ampla revisão da literatura, envolvendo os aspectos cirúrgicos, de Medicina Nuclear e de Anatomia Patológica do linfonodo sentinela. Muitos estudos demonstraram a eficácia do linfonodo sentinela em predizer o comprometimento axilar. Entretanto, existem várias técnicas empregadas para a identificação desse linfonodo, sem haver ainda um consenso em relação ao método mais adequado e reproduzível. A associação do corante vital com o probe, até o presente, é a que tem apresentado os melhores resultados. Também não existe uma padronização do exame patológico intra-operatório do linfonodo sentinela e os índices de falso-negativos encontrados são bastante variáveis. A biópsia do linfonodo sentinela pode oferecer uma alternativa segura à dissecção axilar e com menos efeitos colaterais nos pacientes com axila clinicamente negativa. Entretanto alguns pontos conflitantes devem ser resolvidos antes que o método passe a ser utilizado na prática com o câncer de mama. O objetivo desse trabalho foi discutir os principais aspectos envolvidos no desenvolvimento e na aplicação dessa técnica.

The sentinel lymph node is the first in line to receive lymphatic flow from a primary site in breast cancer. The purpose of this study is to review the most recently results in the literature with this technique. This is a comprehensive review in surgical, nuclear medicine, and pathological aspects of sentinel lymph node in breast cancer. Several reports have demonstrated the accurate prediction of axillary nodal status with sentinel lymph node technique. However, a wide range of different methods and materials has been employed for lymphatic mapping. The association of vital blue and the probe seems to be the most reliable. Also, there is no consensus on the pathologic method for sentinel lymph node examination at the time of surgery. Sentinel node biopsy can offer a safe alternative to routine axillary lymph node dissection for staging patients with breast cancer. The remaining controversial issues must be resolved before sentinel lymph node biopsy becomes a widely accepted part of breast cancer care.