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.

Prospective study: Impact of breast magnetic resonance imaging on oncoplastic surgery and on indications of mastectomy in patients who were previously candidates to breast conserving surgery.

Background: Routine use of magnetic resonance imaging (MRI) in the staging of patients with early breast cancer is still controversial. Oncoplastic surgery (OP) allows for wider resections without compromising the aesthetic results. This study aimed to assess the impact of preoperative MRI on surgical planning and on indications of mastectomy. Methods: Prospective study including T1-T2 breast cancer patients treated between January 2019 and December 2020 in the Breast Unit of the Hospital Nossa Senhora das Graças in Curitiba, Brazil. All patients had indication for breast conserving surgery (BCS) with OP and did a breast MRI after conventional imaging. Results: 131 patients were selected. Indication for BCS was based on clinical examination and conventional imaging (mammography and ultrasound) findings. After undergoing breast MRI, 110 patients (84.0%) underwent BCS with OP and 21 (16.0%) had their surgical procedure changed to mastectomy. Breast MRI revealed additional findings in 52 of 131 patients (38%). Of these additional findings, 47 (90.4%) were confirmed as invasive carcinoma. Of the 21 patients who underwent mastectomies, the mean tumor size was 2.9 cm (± 1,7cm), with all having additional findings on breast MRI (100% of the mastectomies group vs 28.2% of the OP, p<0.01). Of the 110 patients submitted to OP, the mean tumor size was 1,6cm (± 0,8cm), with only 6 (5.4%) presenting positive margins at the final pathology assessment. Conclusion: Preoperative breast MRI has an impact on the OP scenario, bringing additional information that may help surgical planning. It allowed selecting the group with additional tumor foci or greater extension to convert to mastectomy, with a consequent low reoperation rate of 5.4% in the BCS group. This is the first study to assess the impact of breast MRI in the preoperative planning of patients undergoing OP for the treatment of breast cancer.

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.

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.

MicroRNAs miR-142-5p, miR-150-5p, miR-320a-3p, and miR-4433b-5p in Serum and Tissue: Potential Biomarkers in Sporadic Breast Cancer.

Breast cancer (BC) is a heterogeneous disease, and establishing biomarkers is essential to patient management. We previously described that extracellular vesicle-derived miRNAs (EV-miRNAs) miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p in serum discriminated BC from control samples, either alone or combined in a panel. Using these previously described markers, we intend to evaluate whether the same markers identified in EVs are also potential biomarkers in tissue and serum. Expression analysis using RT-qPCR was performed using serum of 67 breast cancer patients (BC-S), 19 serum controls (CT), 83 fresh tumor tissues (BC-T), and 29 adjacent nontumor tissue samples (NT). In addition, analysis from The Cancer Genome Atlas (TCGA) data (832 BC-T and 136 NT) was performed. In all comparisons, we found concordant high expression levels of miR-320a and miR-4433b-5p in BC-S compared to CT in both EVs and cell-free miRNAs (cf-miRNAs). Although miR-150-5p and miR-142-5p were not found to be differentially expressed in serum, panels including these miRNAs improved sensitivity and specificity, supporting our previous findings in EVs. Fresh tissue and data from the TCGA database had, in most comparisons, an opposite behavior when compared to serum and EVs: lower levels of all miRNAs in BC-T than those in NT samples. TCGA analyses revealed reduced expression levels of miR-150-5p and miR-320a-3p in BC-T than those in NT samples and the overexpression of miR-142-5p in BC-T, unlike our RT-qPCR results from tissue in the Brazilian cohort. The fresh tissue analysis showed that all miRNAs individually could discriminate between BC-T and NT in the Brazilian cohort, with high sensitivity and sensibility. Furthermore, combining panels showed higher AUC values and improved sensitivity and specificity. In addition, lower levels of miR-320a-3p in serum were associated with poor overall survival in BC Brazilian patients. In summary, we observed that miR-320a and miR-4433b-5p distinguished BC from controls with high specificity and sensibility, regardless of the sample source. In addition, lower levels of miR-150-5p and higher levels of miR-142-5p were statistically significant biomarkers in tissue, according to TCGA. When combined in panels, all combinations could distinguish BC patients from controls. These results highlight a potential application of these miRNAs as BC biomarkers.

Intraoperative Assessment of Endogenous Microbiota in the Breast.

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.

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.

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.

Intraoperative Assessment of Endogenous Microbiota in the Breast / Avaliação intraoperatória da microbiota endógena da 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 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.

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.

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.

So alike yet so different. Differential expression of the long non-coding RNAs NORAD and HCG11 in breast cancer subtypes.

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.

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.

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].

Association of FOSL1 copy number alteration and triple negative breast tumors.

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.

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.

Proteins play an essential role in the biological processes associated with cancer. Their altered expression levels can deregulate critical cellular pathways and interactive networks. In this study, the mass spectrometry-based label-free quantification followed by functional annotation was performed to investigate the most significant deregulated proteins among tissues of primary breast tumor (PT) and axillary metastatic lymph node (LN) and corresponding non-tumor tissues contralateral (NCT) and adjacent (ANT) from patients diagnosed with invasive ductal carcinoma. A total of 462 proteins was observed as differentially expressed (DEPs) among the groups analyzed. A high level of similarity was observed in the proteome profile of both non-tumor breast tissues and DEPs (n = 12) were mainly predicted in the RNA metabolism. The DEPs among the malignant and non-tumor breast tissues [n = 396 (PTxNCT) and n = 410 (LNxNCT)] were related to pathways of the LXR/RXR, NO, eNOS, eIF2 and sirtuins, tumor-related functions, fatty acid metabolism and oxidative stress. Remarkable similarity was observed between both malignant tissues, which the DEPs were related to metastatic capabilities. Altogether, our findings revealed differential proteomic profiles that affected cancer associated and interconnected signaling processes. Validation studies are recommended to demonstrate the potential of individual proteins and/or pathways as biological markers in breast cancer. SIGNIFICANCE: The proteomic analysis of this study revealed high similarity in the proteomic profile of the contralateral and adjacent non-tumor breast tissues. Significant differences were identified among the proteome of the malignant and non-tumor tissue groups of the same patients, providing relevant insights into the hallmarks, signaling pathways, biological functions, and interactive protein networks that act during tumorigenesis and breast cancer progression. These proteins are suggested as targets of relevant interest to be explored as potential biological markers related to tumor development and metastatic progression in the breast cancer disease.

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.

LOCAL RE-OPERATION AND RECURRENCE IN ONCOPLASTIC BREAST SURGERY / Reoperação e recidiva local em cirurgia oncoplástica mamária

Introduction: In addition to a surgical option, the oncoplastic surgery (OP) is a new philosophy in the mammary oncologic therapy, since it combines concepts of oncologic surgery and plastic surgery. There was a concern that plastic surgery techniques would compromise the oncologic radicalism, leading to an increased risk of tumor recurrence and damage to the patients' survival. The main purpose of the breast conservative surgery (BCS) is to obtain disease-free surgical margins, with a great esthetic-functional result. However, since the advent of this approach, the search for negative margins has been a problem. Despite the efforts to avoid compromised margins, they occur in 20 to 40% of the cases in the traditional BCS, and in many cases leading to the need of reexcision or even to mastectomy. Objective and method: In the analysis of recent studies, the OP role as a reduction factor of new surgeries and local recurrence is questioned. The aim of this paper is to analyze it based on literature review. Conclusion: According to recent studies, the OP became a safe oncological surgical technique that improves both the esthetic result and the disease local control, decreasing the compromised margins with impact on the mitigation of new surgeries rate.

Introdução: A cirurgia oncoplástica (OP) além de opção cirúrgica é uma nova filosofia no tratamento oncológico mamário, pois combina os princípios da cirurgia oncológica com os da cirurgia plástica. Existia um temor de que as técnicas de mamoplastias redutoras pudessem comprometer a radicalidade oncológica, levando a um risco aumentado para recidivas tumorais e prejuízo na sobrevida das pacientes. O objetivo primário da cirurgia conservadora de mama (CC) é obter margens cirúrgicas livres de doença, com bom resultado estético-funcional. Entretanto, desde o advento dessa abordagem, a busca por margens negativas tem sido problemática. Pois, apesar do esforço para se evitar margens comprometidas, elas ocorrem em 20 a 40% dos casos na CC tradicional, levando, em muitas situações, à necessidade de reexcisão ou até mesmo mastectomia. Objetivo e método: Analisando estudos recentes, questiona-se o papel da OP como um fator redutor de reoperações e recidiva local. O objetivo desse artigo é fazer uma discussão embasada em revisão da literatura. Conclusão: Conforme estudos recentes, a OP consagrou-se como técnica cirúrgica oncologicamente segura, com melhora tanto no resultado estético como no controle local da doença, diminuindo margens comprometidas e impactando na atenuação da taxa de reoperações.

Uso de pericárdio bovino na reconstrução mamária imediata com prótese definitiva em paciente previamente irradiada / The use of bovine pericardium in immediate breast reconstructionwith definitive form-stable implant in a previously irradiated patient

A reconstrução mamária em pacientes previamente irradiadas é realizada na maioria das vezes com o uso de retalhos miocutâneos. Esta sempre foi considerada como uma contraindicação re? lativa para o uso de expansores e próteses. Este foi o primeiro relato do uso do pericárdio bovino em reconstrução mamária imediata com prótese definitiva em paciente previamente irradiada. Apesar do alto risco para perda da prótese e para contratura capsular tardia, devido à radiote? rapia, ainda assim, a paciente apresentou pós?operatório sem complicações e, um ano e meio depois, não foi constatada contratura capsular. Além disso, o pericárdio bovino não provocou alterações nos exames de imagem que pudessem comprometer o seu seguimento oncológico. Novos estudos, com séries maiores de pacientes, são necessários para comprovar a segurança e a eficácia do pericárdio bovino na reconstrução mamária.

Breast reconstruction in previously irradiated patients most of times is done with autologus flaps. This condition has been always a contraindication for implants. This is the first report of the use of bovine pericardium in immediate breast reconstruction with definitive implant in a previously irradi? ated patient. Despite of her high risk to extrusion and capsular contracture due to the radiotherapy ef? fects, this patient had no complications on her long?term follow?up. Moreover, the bovine pericardium did not have any alterations in their breast exams. So, future studies are necessary to prove safety and efficacy of this device in breast reconstruction.

Resultados do exame intraoperatório do linfonodo sentinela na Unidade de Mama do Hospital Nossa Senhora das Graças em Curitiba / Intraoperatory sentinel node exam at the Hospital NossaSenhora das Graças Breast Unit in Curitiba

A biópsia do linfonodo sentinela (LS) é o procedimento padrão para as pacientes com axila clinicamente negativa. O seu exame intraoperatório ainda gera dificuldades na sua abordagem. Assim, o objetivo deste estudo foi avaliar a eficácia desse exame no câncer de mama. Foram avaliadas 342 pacientes que foram operadas na Unidade de Mama do Hospital Nossa Senhora das Graças em Curitiba (PR), no período de 2000 a 2012. No exame intraoperatrório eram rea lizados cortes longitudinais, ao longo do maior eixo, a cada 2 ou 3mm. Em seguida eram feitos imprints em cada face de cada fatia e, então, realizavam se cortes histológicos em criostato em três níveis. Tanto os imprints quanto os cortes eram corados com azul de toluidina. Em sua maio ria eram tumores T1c (n=151), e 60 (17,5%) delas apresentaram axila comprometida no exame definitivo. A acurácia foi de 92%, o valor preditivo negativo, de 91% e a taxa de falso negativo, de 8%. Não foram encontrados fatores de risco significativos para falência da técnica dentro dos parâmetros estudados.

Sentinel node (SN) biopsy is the standard of care for patients with clinically negative axilla. However, in traoperatory pathological exam remains as a controversial issue. So, the aim of this study was to evaluate its efficacy in 342 breast cancer patients operated at the Hospital Nossa Senhora das Graças Breast Unit in Curitiba (PR), in the period between 2000 2012. In the intraoperatory evaluation, all SNs were cutted in the major axis, in three levels, combining frozen sections with imprints, using toluidin blue. The majority of patients were T1c (n=151), and 60 (17.5%) had positive axila in the definitive pathology evaluation. Accuracy was 92%, predictive negative value was 91%, and false negative rate was 8%. We did not find any significant risk factor for false negative SN in this series.