Three-dimensional Simulation on Patient-reported Outcomes Following Oncoplastic and Reconstructive Surgery of the Breast: A Randomized Trial.

Background: Three-dimensional (3D) imaging using computer simulations is an evolving technology. There is a lack of strong data on the use of this technology for oncoplastic (OP) and reconstructive surgery. Methods: A prospective, randomized, single-center trial including breast cancer patients undergoing OP or mastectomy with immediate breast reconstruction with implant (IBR) enrolled from November 2019 to October 2021 at the Hospital Nossa Senhora das Graças, Breast Unit in Curitiba, Brazil. Both patients undergoing OP and those in the IBR group were randomized to undergo 3D imaging and simulation of postoperative results (intervention group) or 3D imaging without simulation (control group). All patients were invited to complete a patient-reported outcome (BREAST-Q) expectations module and breast reconstruction or reduction/mastopexy module before and 6 months after surgery. Results: A total of 96 patients were enrolled. Sixty-nine patients (45 OP and 24 IBR) completed the pre- and postoperative questionnaires and were randomized for the simulation. Women in the OP group had higher expectations for breast appearance when clothed than those in the IBR implant group (93.4 ± 16.3 versus 82.9 ± 26.5; P = 0.03). The intervention group was more satisfied with information than the control group (P = 0.021). Both patients who underwent OP and IBR believed that the 3D simulation helped them understand the surgical process (86.6% and 75%, respectively). Conclusions: Preoperative 3D simulation significantly improved patient's satisfaction with information and did not decrease postoperative satisfaction with the outcomes. The incorporation of preoperative 3D simulation may be a valuable tool in breast reconstruction.

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.

High-throughput proteomics of breast cancer subtypes: Biological characterization and multiple candidate biomarker panels to patients' stratification.

BACKGROUND AND AIMS: The actual classification of breast tumors in subtypes represents an attempt to stratify patients into clinically cohesive groups, nevertheless, clinicians still lack reproducible and reliable protein biomarkers for breast cancer subtype discrimination. In this study, we aimed to access the differentially expressed proteins between these tumors and its biological implications, contributing to the subtype's biological and clinical characterization, and with protein panels for subtype discrimination. METHODS: In our study, we applied high-throughput mass spectrometry, bioinformatic, and machine learning approaches to investigate the proteome of different breast cancer subtypes. RESULTS: We identified that each subtype depends on different protein expression patterns to sustain its malignancy, and also alterations in pathways and processes that can be associated with each subtype and its biological and clinical behaviors. Regarding subtype biomarkers, our panels achieved performances with at least 75% of sensibility and 92% of specificity. In the validation cohort, the panels obtained acceptable to outstanding performances (AUC = 0.740 to 1.00). CONCLUSIONS: In general, our results expand the accuracy of breast cancer subtypes' proteomic landscape and improve the understanding of its biological heterogeneity. In addition, we identified potential protein biomarkers for the stratification of breast cancer patients, improving the repertoire of reliable protein biomarkers. SIGNIFICANCE: Breast cancer is the most diagnosed cancer type worldwide and the most lethal cancer in women. As a heterogeneous disease, breast cancer tumors can be classified into four major subtypes, each presenting particular molecular alterations, clinical behaviors, and treatment responses. Thus, a pivotal step in patient management and clinical decisions is accurately classifying breast tumor subtypes. Currently, this classification is made by the immunohistochemical detection of four classical markers (estrogen receptor, progesterone receptor, HER2 receptor, and the Ki-67 index); however, it is known that these markers alone do not fully discriminate the breast tumor subtypes. Also, the poor understanding of the molecular alterations of each subtype leads to a challenging decision-making process regarding treatment choice and prognostic determination. This study, through high-throughput label-free mass-spectrometry data acquisition and downstream bioinformatic analysis, advances in the proteomic discrimination of breast tumors and achieves an in-depth characterization of the subtype's proteomes. Here, we indicate how the variations in the subtype's proteome can influence the tumor's biological and clinical differences, highlighting the variation in the expression pattern of oncoproteins and tumor suppressor proteins between subtypes. Also, through our machine-learning approach, we propose multi-protein panels with the potential to discriminate the breast cancer subtypes. Our panels achieved high classification performance in our cohort and in the independent validation cohort, demonstrating their potential to improve the current tumor discrimination system as complements to the classical immunohistochemical classification.

A three-sequence dynamic contrast enhanced abbreviated MRI protocol to evaluate response to breast cancer neoadjuvant chemotherapy.

PURPOSE: To develop an ABP-MRI to evaluate response to NAC for invasive breast carcinoma. STUDY TYPE: A single-center, cross-sectional study. SUBJECTS: A consecutive series of 210 women with invasive breast carcinoma who underwent breast MRI after NAC between 2016 and 2020. FIELD STRENGTH/SEQUENCE: 1.5 T / Dynamic contrast-enhanced. ASSESSMENT: MRI scans were independently reevaluated, with access to dynamic contrast-enhanced without contrast and to the first, second, and third post-contrast time (ABP-MRI 1-3). STATISTICAL TESTS: The diagnostic performance of the ABP-MRIs and the Full protocol (FP-MRI) were analyzed. The Wilcoxon non-parametric test (p-value <0.050) was used to compare the capability in measuring the most extensive residual lesion. RESULTS: The median age was 47 (24-80) years. ABP-MRI 1 showed higher specificity (84.6%; 77/91) but a higher probability of false-negatives (16.8%) and lower sensitivity (83.2%; 99/119) than ABP-MRI 2,3 and the FP-MRI, which were identical in specificity (81.3%; 74/91), probability of false-negatives (8.4%), and sensitivity (91.6%; 109/119). ABP-MRI 2 showed a mean underestimation of only 0.03 cm in the measurement of the longest axis of the residual lesion (p = 0.008) with an average reduction in the acquisition time of 75%, compared with the FP-MRI. CONCLUSION: ABP-MRI 2 showed diagnostic performance equivalent to the FP-MRI with a 75% reduction in the acquisition time.

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.

Prepectoral Direct-to-Implant Breast Reconstruction without Placement of Acellular Dermal Matrix or Mesh after Nipple-Sparing Mastectomy.

BACKGROUND: The aim of this study was to report the results of prepectoral direct-to-implant reconstruction in nipple-sparing mastectomy without acellular dermal matrices or mesh. METHODS: A multicenter cohort of patients undergoing prophylactic or therapeutic nipple-sparing mastectomy was included from 2013 to 2020. All sizes and types of breasts were included, except those with previously failed reconstruction, previous radiotherapy with severe skin damage, locally advanced breast cancer, gigantomasty, severe degree of ptosis, tumors close to the nipple-areola complex (<1 cm on magnetic resonance imaging), or combined autologous-based reconstruction. RESULTS: A total of 280 immediate breast reconstructions were performed in 195 patients. The mean age was 45 years and 32.8 percent of patients were postmenopausal. The mean follow-up period was 16.5 (±17.43) months. Eighty-five patients (43.6 percent) underwent bilateral mastectomy; 116 mastectomies (41.4 percent) were prophylactic and 164 (58.6 percent) were therapeutic. Sixty-eight reconstructions (24 percent) had at least one acute complication, the most common being implant explantation (9.2 percent), which was more frequent in smokers. Late complications included rippling (grades 3 and 4) in seven cases (3.8 percent) and capsular contracture (Baker II through IV) in 29 cases (15.7 percent) [22 Baker II (11.9 percent), six Baker III (3.3 percent), and one Baker IV (0.5 percent)]. One implant rotation was observed. No deformity animation was observed. Cosmetic results were considered good or excellent in 87.3 percent of patients. CONCLUSIONS: Overall complications were similar to those reported in acellular dermal matrices, mesh, or subpectoral series, except for a higher explantation rate. This technique is safe and economically advantageous, as it is a one-stage technique without acellular dermal matrices and mesh. These are preliminary data and larger and comparative studies are needed. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Transcribed Ultraconserved Regions Are Associated with Clinicopathological Features in Breast Cancer.

Ultraconserved regions (UCRs) are 481 genome segments, with length longer than 200 bp, that are 100% conserved among humans, mice, and rats. The majority of UCRs are transcriptionally active (T-UCRs) as many of them produce non-coding RNAs. In a previous study, we evaluated the expression level of T-UCRs in breast cancer (BC) patients and found that 63% of transcripts correlated with some clinical and/or molecular parameter of BC. In this study, we delved into the expression levels of 12 T-UCRs and correlated them with clinicopathological parameters, immunohistochemical markers, and overall survival in two breast cancer cohorts: TCGA and Brazilian patients. We found that uc.268 is more expressed in TCGA patients under 40 years of age, associated with progesterone receptor (PR) and estrogen receptor (ER), and its high expression is found in luminal A. Lower uc.84 and uc.376 were respectively observed in metastatic and stage IV tumors associated with good prognostic in luminal B. Moreover, uc.84 was only related to the HER2+, while uc.376 was related to ER+ and PR+, and HER2+. A panel composed of uc.147, uc.271, and uc.427 distinguished luminal A from triple negative patients with an AUC of 0.9531 (sensitivity 92.19% and specificity 86.76%). These results highlight the potential role of T-UCRs in BC and provide insights into the potential application of T-UCRs as 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.

Trends in breast cancer surgery in private patients under opportunistic screening / Tendências na cirurgia de câncer de mama em pacientes de um serviço privado sob rastreio oportunístico

Objective: This study aims to determine the evolution of staging and surgical treatment in patients with breast cancer in a private clinic over the last 40 years. Methods: Retrospective descriptive observational study, through statistical analysis of the medical records of 2105 patients treated at a private clinic in Curitiba, Paraná, between 1977 and 2017. Results: Data analyzed from 2,105 patients diagnosed with breast cancer revealed that, over time, radical surgeries predominated when compared to conservative ones. However, when analyzed proportionally over the years, it is possible to observe an inversion of the surgical modalities. It was demonstrated that from 1977 to 2017, there was a 273% increase in the number of conservative surgeries and a 45.5% decrease in mastectomies. In addition to this data, there was a decrease in the number of axillary emptying and, consequently, of positive sentinel lymph nodes. In addition, tumors diagnosed early (T1) have increased over the years. Conclusion: Patients had an early diagnosis of the disease, resulting in less invasive surgical treatments and, consequently, lower morbidity and mortality.

Objetivo: A pesquisa visa determinar a evolução do estadiamento e do tratamento cirúrgico em pacientes com câncer de mama em uma clínica privada, nos últimos 40 anos. Métodos: Estudo observacional descritivo retrospectivo, por meio da análise estatística dos prontuários de 2105 pacientes atendidas em clínica privada em Curitiba, Paraná, entre 1977 e 2017. Resultados: Dados analisados de 2.105 pacientes diagnosticadas com câncer de mama revelaram que, ao longo do tempo, as cirurgias radicais predominaram quando comparadas às cirurgias conservadoras. No entanto, quando analisadas proporcionalmente ao longo dos anos, é possível constatar uma inversão das modalidades cirúrgicas. Demonstrou-se que de 1977 a 2017, houve aumento de 273% do número das cirurgias conservadoras e queda de 45,5% das mastectomias. Associado a esse dado, notou-se diminuição do número de esvaziamento axilar e consequentemente de linfonodos sentinela positivos. Além disso, os tumores diagnosticados em fase inicial (T1) aumentaram ao longo dos anos. Conclusão: As pacientes tiveram um diagnóstico em estadiamento mais precoce da doença, proporcionando tratamentos cirúrgicos menos invasivos e, consequentemente, menor morbidade.

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.

HER2-expressing breast tumors are associated with breast cancer stem-cell phenotype CD44+/CD24- / Tumores de mama que superexpressam HER2 estão associados ao fenótipo de células-tronco tumorais CD44+/CD24-

ABSTRACT INTRODUCTION: According to the cancer stem-cell theory, tumors originate from a small population of cancer stem cells, which lose the mechanism of self-regulation and begin to differentiate and proliferate indefinitely. The CD44+/CD24- phenotype may be considered a stem-cell marker in breast cancer. OBJECTIVE: To evaluate the correlation between CD44+/CD24- phenotype and different molecular subtypes of breast cancer in invasive ductal carcinoma samples. METHODS: The expression of CD44, CD44v6, and CD24 markers was investigated in 133 cases of invasive mammary carcinoma with immunohistochemistry. CD44+/CD24- phenotype was identified and correlated with the molecular subtypes and classical prognostic factors such as age, histological grade, tumor size, and lymph node status. RESULTS: Eighteen (14%) cases were positive for CD44+/CD24- (CD44+/CD24- or CD44v6+/CD24-) phenotype; among these, 11.1%, 27.8%, 38.9%, and 22.2% were luminal, luminal B-human epidermal growth factor receptor 2 (HER2), HER2, and triple-negative subtype, respectively. CD44+/ CD24- phenotype was more common in HER2 subgroup (p = 0.0197). CONCLUSION: CD44+/CD24- phenotype was correlated with molecular subtypes of breast cancer. The highest expression of CD44+/CD24- phenotype was reported in patients with HER2+ disease, a molecular subtype associated with more aggressive behavior and worse prognosis.

RESUMO INTRODUÇÃO: De acordo com a teoria das células-tronco tumorais, os tumores são originários de uma pequena população de células-tronco que perdem o mecanismo de autorregulação e começam a se diferenciar e proliferar indefinidamente. O fenótipo CD44+/CD24- pode ser considerado um marcador de células-tronco tumorais no câncer de mama. OBJETIVO: Avaliar a correlação entre o fenótipo CD44+/CD24- e os diferentes subtipos moleculares do câncer de mama em amostras de carcinoma ductal invasor. MÉTODOS: A expressão dos marcadores CD44, CD44v6 e CD24 foi investigada em 133 casos de carcinoma mamário invasor por meio de imuno-histoquímica. O fenótipo CD44+/CD24- foi identificado e correlacionado com os subtipos moleculares e os fatores prognósticos clássicos, como idade, grau histológico, tamanho do tumor e status do linfonodo. RESULTADOS: Dezoito (14%) casos foram positivos para o fenótipo CD44+/CD24- (CD44+/CD24- ou CD44v6+/CD24-), sendo 11, 1%, 27, 8%, 38, 9% e 22, 2% dos subtipos luminal, luminal B-human epidermal growth factor receptor 2 (HER2), HER2 e triplo negativo, respectivamente. O fenótipo CD44+/CD24- foi mais comum no subgrupo HER2 (p = 0, 0197). CONCLUSÃO: O fenótipo CD44+/CD24- foi correlacionado com os subtipos moleculares do câncer de mama. A maior expressão do fenótipo CD44+/CD24- foi encontrada em pacientes com doença HER2+, subtipo molecular associado a um comportamento mais agressivo e a um pior prognóstico.

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.

Down regulation of ADAM33 as a Predictive Biomarker of Aggressive Breast Cancer.

Breast cancer is a heterogeneous disease with differences in its clinical, molecular and biological features. Traditionally, immunohistochemical markers together with clinicopathologic parameters are used to classify breast cancer and to predict disease outcome. Triple-negative breast cancer (TNBC) is a particular type of breast cancer that is defined by a lack of expression of hormonal receptors and the HER2 gene. Most cases of TNBC also have a basal-like phenotype (BLBC) with expression of cytokeratin 5/6 and/or EGFR. A basal marker alone is insufficient for a better understanding of the tumor biology of TNBC. In that regard, the ADAM33 gene is silenced by DNA hypermethylation in breast cancer, which suggests that ADAM33 might be useful as a molecular marker. In the present study, we have produced monoclonal antibodies against the ADAM33 protein and have investigated the role of ADAM33 protein in breast cancer. We used 212 breast tumor samples and lower levels of ADAM33 were correlated with TNBC and basal-like markers. A lower level of ADAM33 was also correlated with shorter overall survival and metastasis-free survival and was considered an independent prognostic factor suggesting that ADAM33 is a novel molecular biomarker of TNBC and BLBC that might be useful as a prognostic factor.

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.

Oncoplastic principles in breast conserving surgery.

Oncoplastic surgery (OP) represents a major advance in breast cancer surgery. It is based on three principles: ideal oncology surgery with free margins and adequate local control of disease, immediate breast reconstruction and symmetry, with the transposition of plastic surgery techniques into breast cancer surgery. Its original focus was to improve the quality of life of patients undergoing oncological treatments that can be more effective from the aesthetic-functional point of view than the traditional breast conserving techniques. As it happens with all changes of paradigms, it brings new challenges for the traversal formation of all involved in the treatment of breast cancer. Besides that, it opens to new perspectives of surgical research related to the aesthetic results, quality of life and local control, as well as optimization of operative timing and reduction of both adverse effects and costs. The aim of this review was to present the principles of this approach and the main techniques applied, evaluating its indications and limits in conservative breast cancer surgery.

Immediate breast reconstruction in pregnancy and lactation / Reconstrução mamária imediata na gestação e na lactação

Introduction: Pregnancy-associated breast cancer(PABC) incluides breast cancer diagnosed during pregnancy and within a year after delivery. At least 10% of the patients with breast cancer who are younger than 40 years of age are pregnant at their diagnosis. Although mastectomy is the most frequent indication, there are no data about immediate breast reconstruction, and most authors recommend delayed reconstruction. Objective: The purpose of this paper was to present a model that allows immediate breast reconstruction in this complex group of patients, which no compromise neither oncologic treatment nor the fetus evolution. Methods: This study was carried out as retrospective and prospective analysis of consecutive PABC patients who had undergone mastectomy, axillary dissection and immediate breast reconstruction in the Breast Unit of Nossa Senhora das Graças Hospital, in Curitiba (PR), Brazil, from March 2004 until July 2008. Results: From a total number of 598 cases of invasive breast cancer, 10 PABC cases (1.7%) were selected. These patients were younger and with more aggressive tumors than non-pregnant ones. Breast reconstructions were performed following a specific decision model designed in our Unit. First trimester patient (n=1) was submitted to immediate reconstruction in one-step surgery with breast implants and contra-lateral symmetry. Second and third trimester patients (n=2) were submitted to temporary expanders. Lactation patients (n=5) were submitted to temporary expanders, or one-step surgery with implants in cases of lactation ceased at least three months ago (n=l). No surgical complications or delay in adjuvant therapy were observed. Only one patient needed postoperative radiotherapy, resulting in Baker 2 capsular contracture. Conclusions: All the patients were alive without disease in this group, and the fetus evolutions were not compromised by the surgery. This reconstructive approach minimizes the effects of mastectomy...

Introdução: Câncer de mama associado à gestação (CAG) inclui todos aqueles casos diagnosticados durante o período da gestação até aqueles detectados um ano depois, no período da lactação. Até 10% das pacientes diagnosticadas com câncer de mama antes dos 40 anos estão grávidas. Embora a mastectomia seja a indicação mais frequente nesse grupo, não existem dados sobre a reconstrução mamária imediata, e a maioria dos autores indica que se adie a reconstrução. Objetivo: O objetivo deste estudo foi apresentar um modelo que permite a reconstrução mamária imediata nesse grupo complexo de pacientes, sem comprometimento para o tratamento oncológico ou para a evolução fetal. Métodos: Trata-se de uma série de pacientes consecutivas com CAG, acompanhadas de maneira retrospectiva e prospectiva, e submetidas à mastectomia e reconstrução mamária imediata na Unidade de Mama do Hospital Nossa Senhora das Graças em Curitiba, no período entre Março de 2004 até Julho de 2008. Resultados: Entre um total de 598 casos de carcinomas invasivos, 10 (1,7%) CAG foram selecionados para este estudo. Essas pacientes eram mais jovens e com tumores biologicamente mais agressivos do que as pacientes fora do período associado com a gestação. A decisão sobre a reconstrução mamária imediata seguiu um protocolo específico criado dentro da unidade. Uma paciente do primeiro trimestre (n=1) foi submetida à reconstrução mamária imediata com prótese definitiva e simetrização. Duas pacientes do segundo e terceiros trimestres (n=2) foram submetidas à reconstrução mamária imediata com expansores. As pacientes diagnosticadas durante a lactação foram submetidas à reconstrução imediata com expansores temporários (n=5) e uma (n=1), cuja lactação tinha cessado há três meses, foi submetida à reconstrução mamária imediata com prótese definitiva e simetrização imediata. Não foram observadas complicações ou atraso no início do tratamento adjuvante neste grupo de pacientes. Uma paciente necessitou...