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.

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.

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.

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.

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.

IMPACT OF PREOPERATORY MAGNETIC RESONANCE IMAGING IN ONCOPLASTIC SURGERY / Impacto da ressonância magnética pré-operatória na cirurgia oncoplástica

Objective: There is no data about magnetic resonance image (MRI) impact in oncoplastic surgery (OP). The objective of this study was to evaluate the impact of MRI on the surgical planning and the changes of conduct in patients with initial breast cancer and candidates to perform the OP. Methods: This is a prospective cohort of 60 patients who were candidates to OP between January 2013 and July 2014. All of them underwent to a preoperative MRI, in addition to mammography (MG) and ultrasound (US). Any additional tumor in the MRI classified as BIRADS 4-5 were biopsied or marked with carbon and radiotracer in order to be localized during the surgery. Surgical impact of additional MRI findings were evaluated as to changes of approach to mastectomy or to wider resection. Results: Of the patients, 29/60 (48.3%) had additional findings on MRI, 16/29 (55%) were multifocal tumors, 1/29 (3.4%) was multicentric, 5/29 (17%) were contralateral tumors, and 9/29 (31%) presented tumor size larger than 10 mm in the MRI. Of 22 patients who showed additional lesions on MRI, 15 (68.2%) had invasive carcinomas in the definitive anatomopathological exam. Sensibility of MRI was higher in the estimation of the tumor size. Of the patients, 12/60 (20%) underwent to mastectomy, and 17/60 (28.3%) to wider resections. Only 5% of patients had positive margins in the entire group, and in the group of patients that had additional findings on MRI only 3.4% had positive margins. Conclusions: MRI is better than MG and US in evaluating the extension of the tumor, and in the detection of multicentricity, multifocality and bilaterality. In consequence, it contributed in this series for a better surgical planning in OP with a low rate of compromised margins and re-operations.

Objetivo: Não há dados sobre o impacto da imagem de ressonância magnética (RM) na cirurgia oncoplástica. O objetivo deste trabalho foi avaliar o impacto da RM no planejamento cirúrgico e nas mudanças de conduta em pacientes com câncer de mama inicial e candidatas a realizar a cirurgia oncoplástica. Métodos: Trata-se de uma coorte prospectiva de 60 pacientes que foram candidatas à cirurgia oncoplástica entre janeiro de 2013 e julho de 2014. Todos elas foram submetidas a uma RM pré-operatória, além de mamografia (MG) e ultrassom (US). Qualquer tumor adicional na RM classificada como BIRADS 4-5 foi biopsiado ou marcado com carvão e ROLL para serem localizados durante a cirurgia. O impacto cirúrgico dos achados adicionais da RM foi avaliado quanto a mudanças para mastectomia ou ressecção mais ampla. Resultados: Das pacientes, 29/60 (48,3%) apresentaram achados adicionais na ressonância magnética, 16/29 (55%) foram tumores multifocais, 1/29 (3,4%) foi multicêntrico, 5/29 (17%) foram tumores contralaterais e 9/29 (31%) apresentaram tamanho de tumor maior que 10 mm na RM. Das 22 pacientes que apresentaram lesões adicionais na RM, 15 (68,2%) apresentaram carcinomas invasivos no exame anatomopatológico definitivo. A sensibilidade da RM foi maior na estimativa do tamanho do tumor. Das pacientes, 12/60 (20%) foram submetidas à mastectomia e 17/60 (28,3%) a ressecções mais amplas. Apenas 5% das pacientes apresentaram margens positivas em todo o grupo. No grupo de pacientes que apresentaram resultados adicionais na RM, apenas 3,4% tiveram margens positivas. Conclusões: A RM é melhor que a MG e o US na avaliação da extensão do tumor e na detecção de tumores multicêntricos, multifocais e bilaterais. Em consequência, contribuiu nesta série para um melhor planejamento cirúrgico na cirurgia oncoplástica com baixa taxa de margens comprometidas e reexcisão.

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.