A Case Study of a Rare Undifferentiated Spindle Cell Sarcoma of the Penis: Establishment and Characterization of Patient-Derived Models.

Rare sarcomas present significant treatment challenges compared to more prevalent soft tissue sarcomas due to limited treatment options and a poor understanding of their biology. This study investigates a unique case of penile sarcoma, providing a comprehensive morphological and molecular analysis. Through the creation of experimental patient-derived models-including patient-derived xenograft (PDX), 3D, and monolayer primary cultures-we successfully replicated crucial molecular traits observed in the patient's tumor, such as smooth muscle actin and CD99 expression, along with specific mutations in genes like TSC2 and FGFR4. These models are helpful in assessing the potential for an in-depth exploration of this tumor's biology. This comprehensive approach holds promise in identifying potential therapeutic avenues for managing this exceedingly rare soft tissue sarcoma.

Low rate of complications in nipple-sparing mastectomy for patients with BRCA1 and BRCA2 mutation.

Background: To describe the indications and outcomes of BRCA mutation carriers undergoing nipple-sparing mastectomy (NSM). Methods: In this retrospective study, 76 BRCA mutation carriers with no cancer who opted to undergo risk reduction NSM or diagnosed with breast cancer (BC) who opted to undergo therapeutic NSM were included. Results: Indications for NSM: cancer treatment (n = 33), bilateral risk reduction (n = 39) and contralateral prophylactic NSM (n = 4). In a mean follow-up of 45 months (median: 30 months), one patient (2.5%) undergoing risk-reducing NSM developed a new BC. One (3%) local, one (3%) ipsilateral axillary and one (3%) distant recurrence were observed in BC patients. No partial or total nipple necrosis occurred. Conclusion: NSM is safe for reducing the risk of BC development in BRCA mutation carriers and for treating cancer.

Gynecologic and Breast Cancers: What's New in Chemoresistance and Chemosensitivity Tests?

Gynecological and breast cancers affect women's health worldwide. Although chemotherapy is one of the principal treatments for cancer, it also has limitations owing to toxicity and tumor resistance to the drugs used. Thus, individualized treatment based on personal tumor characteristics is essential for improving therapeutic outcomes and patient survival. Chemoresistance and chemosensitivity tests can be useful for predicting tumor response and guiding chemotherapy choices. This methodology has already been applied to breast, ovarian, cervical, and endometrial cancers, identifying successfully which drugs cause resistance and sensitivity responses for each individual person, influencing their progression-free survival and overall response. In addition, more recent techniques, such as organoids and patient-derived xenografts, can also recapitulate patients' tumor characteristics and contribute to chemo response evaluation. Therefore, this review compiles information on chemoresistance and chemosensitivity tests performed in gynecologic and breast cancers and their main results for women's health improvement.

A New Brazilian Device for Cervical Cancer Screening: Acceptability and Accuracy of Self-sampling.

OBJECTIVE: To evaluate the accuracy and patient acceptability toward self-sampling using a new device - SelfCervix® - for detecting HPV-DNA. METHODS: A total of 73 women aged 25-65 who underwent regular cervical cancer screening from March to October 2016 were included. Women performed self-sampling followed by a physician-sampling, and the samples were analyzed for HPV-DNA. After that, patients were surveyed about their acceptability of self-sampling. RESULTS: HPV-DNA detection rate of self-sampling presented high accuracy and was similar to physician-collection. Sixty-four (87.7%) patients answered the acceptability survey. Most patients (89%) considered the self-sampling comfortable, and 82.5% preferred self-sampling to physician-sampling. The reasons cited were time-saving and convenience. Fifty-one (79.7%) reported that they would recommend self-sampling. CONCLUSION: Self-sampling using the new Brazilian device SelfCervix® is not inferior in HPV-DNA detection rate compared with physician-collection, and patients are supportive of the method. Therefore, it might be an option to reach under-screened populations in Brazil.

OBJETIVO: Avaliar a acurácia e aceitabilidade da auto-coleta utilizando um novo coletor - SelfCervix® - para a detecção de DNA de HPV. MéTODOS: Foram incluídas no estudo 73 mulheres com idade entre 25­65 anos que realizaram seu rastreamento regular do câncer de colo do útero entre Março e Outubro de 2016. Estas mulheres realizaram a auto-coleta, seguida de coleta profissional e as amostras foram analisadas para a presença de DNA de HPV. Após, elas responderam um questionário sobre a experiência da auto-coleta. RESULTADOS: As taxas de detecção de DNA de HPV por auto-coleta foram altas e similares as da coleta profissional. Sessenta e quatro (87,7%) pacientes responderam o questionário de experiência. A maioria (89%) considerou a auto-coleta confortável, e 82,5% preferiram o método comparado a coleta profissional. As razões citadas foram economia de tempo e conveniência. Cinquenta e uma (79,7%) mulheres confirmaram que recomendariam a auto-coleta. CONCLUSãO: Auto-coleta utilizando o novo coletor desenvolvido no Brasil não é inferior na detecção de DNA de HPV quando comparada a coleta profissional, e apresenta uma boa aceitabilidade pelas mulheres. Desta maneira, pode ser uma opção para alcançar populações que não realizam o rastreamento padrão.

A New Brazilian Device for Cervical Cancer Screening: Acceptability and Accuracy of Self-sampling / Um Novo Dispositivo Brasileiro para Diagnóstico de Câncer Cervical: Aceitabilidade e Precisão da Autoamostragem

Abstract Objective To evaluate the accuracy and patient acceptability toward self-sampling using a new device - SelfCervix® - for detecting HPV-DNA. Methods A total of 73 women aged 25-65 who underwent regular cervical cancer screening from March to October 2016 were included. Women performed self-sampling followed by a physician-sampling, and the samples were analyzed for HPV-DNA. After that, patients were surveyed about their acceptability of self-sampling. Results HPV-DNA detection rate of self-sampling presented high accuracy and was similar to physician-collection. Sixty-four (87.7%) patients answered the acceptability survey. Most patients (89%) considered the self-sampling comfortable, and 82.5% preferred self-sampling to physician-sampling. The reasons cited were time-saving and convenience. Fifty-one (79.7%) reported that they would recommend self-sampling. Conclusion Self-sampling using the new Brazilian device SelfCervix® is not inferior in HPV-DNA detection rate compared with physician-collection, and patients are supportive of the method. Therefore, it might be an option to reach under-screened populations in Brazil.

Resumo Objetivo Avaliar a acurácia e aceitabilidade da auto-coleta utilizando um novo coletor - SelfCervix® - para a detecção de DNA de HPV. Métodos Foram incluídas no estudo 73 mulheres com idade entre 25-65 anos que realizaram seu rastreamento regular do câncer de colo do útero entre Março e Outubro de 2016. Estas mulheres realizaram a auto-coleta, seguida de coleta profissional e as amostras foram analisadas paraa presença de DNA de HPV. Após, elas responderam um questionário sobre a experiência da auto-coleta. Resultados As taxas de detecção de DNA de HPV por auto-coleta foram altas e similares as da coleta profissional. Sessenta e quatro (87,7%) pacientes responderam o questionário de experiência. A maioria (89%) considerou a auto-coleta confortável, e 82,5% preferiram o método comparado a coleta profissional. As razões citadas foram economia de tempo e conveniência. Cinquenta e uma (79,7%) mulheres confirmaram que recomendariam a auto-coleta. Conclusão Auto-coleta utilizando o novo coletor desenvolvido no Brasil não é inferior na detecção de DNA de HPV quando comparada a coleta profissional, e apresenta uma boa aceitabilidade pelas mulheres. Desta maneira, pode ser uma opção para alcançar populações que não realizam o rastreamento padrão.

Nipple-sparing Mastectomy with Immediate Implant-based Reconstruction for Patients with Pure Ductal Carcinoma in Situ.

OBJECTIVE: The presence of an extensive intraductal component is associated to an increasing risk of relapse in the nipple-areola complex. The aim of the present study was to evaluate the outcomes of patients diagnosed with ductal carcinoma in situ (DCIS) who underwent nipple-sparing mastectomy (NSM) with immediate breast reconstruction using silicone implants. METHODS: We retrospectively analyzed the postoperative complications and oncological safety of 67 breast cancer patients diagnosed with pure DCIS who underwent NSM with immediate breast reconstruction using silicone implants between 2004 and 2018. RESULTS: Among the 127 NSM procedures performed, 2 hematomas (1.5%) and 1 partial nipple necrosis (0.7%) were observed. After a mean follow-up of 60 months, the local recurrence rate was of 8.9%, the disease-free survival rate was of 90%, and 1 of the patients died. CONCLUSION: Despite the local recurrence rate, we showed that NSM with immediate breast reconstruction using silicone implants is a feasible surgical approach, with a low rate of complications and high survival rates for patients with a diagnosis of pure DCIS when breast-conserving surgery is not an option.

OBJETIVO: A presença de componente intraductal extenso é associada ao risco aumentado de recorrência no complexo aréolo-mamilar. O objetivo deste estudo foi avaliar os resultados de pacientes diagnosticados com carcinoma ductal in situ (CDIS) submetidas a adenomastectomia (nipple-sparing mastectomy, NSM, em inglês) com reconstrução mamária imediata utilizando prótese de silicone. MéTODOS: Restrospectivamente, foram analisadas as complicações pós-operatórias e a segurança oncológica de 67 pacientes com câncer de mama diagnosticadas com CDIS puro, e submetidas a NSM com reconstrução mamária imediata utilizando prótese de silicone, entre 2004 e 2018. RESULTADOS: Entre os 127 procedimentos realizados, 2 hematomas (1,5%) e 1 necrose parcial de mamilo (0,7%) foram observados. Após um período médio de 60 meses de seguimento, a taxa de recorrência local foi de 8,9%, a sobrevida livre de doença, de 90%, e apenas 1 paciente foi a óbito. CONCLUSãO: Apesar da taxa de recorrência local, demostrou-se que NSM com reconstrução mamária imediata com prótese de silicone é um procedimento viável, com baixa taxa de complicação e alta sobrevida para pacientes com diagnóstico de CDIS puro quando a cirurgia conservadora da mama não é uma opção.

Salvage Nipple-sparing Mastectomy for Patients with Breast Cancer Recurrence: A Case Series of Brazilian Patients / Mastectomia preservadora de mamilo para pacientes com recidiva de câncer de mama: Uma série de casos de pacientes brasileiras

Abstract Objective Few studies analyzed the safety of salvage nipple-sparing mastectomy (NSM) for local relapse treatment. We evaluated the outcomes of patients with indications for mastectomy who chose to undergo NSM for ipsilateral breast tumor recurrence (IBTR). Methods Between January 2001 and December 2018, we evaluated 24 women who underwent NSM for local relapse after conservative surgery. Results Thepatientswere followedupfor amean time of132months since thefirst surgery. After the NSM, 5 (20.8%) patients were diagnosed with local recurrence and only 1 (4.2%) patient died. The patients presented 4.8% (2) of partial and 2.4% (1) of total nipple necrosis. Conclusion In this long-term follow-up since the first surgery, we observed low rates of complication and good survival, although associated with high local recurrence in patients diagnosed with IBTR undergoing NSM as salvage surgery.We demonstrated that NSMmay be considered after IBTR for patients who did not want to undergo total mastectomy.

Resumo Objetivo Há poucos estudos sobre a segurança de se realizar adenomastectomia (nipple-sparing mastectomy, NSM, em inglês) para tratamento de recidiva local. O objetivo deste estudo foi avaliar os resultados de pacientes com indicação para mastectomia que optaram por se submeter a NSM para o tratamento de recorrência local. Métodos Foram analisadas 24 pacientes submetidas a NSM para tratamento de recidiva local após tratamento conservador entre janeiro de 2001 e dezembro de 2018. Resultados As pacientes foramacompanhadas por um períodomédio de 132meses a partir da primeira cirurgia. Após a NSM, 5 (20,8%) pacientes foram diagnosticadas com recorrência local, e apenas 1 paciente foi a óbito. As pacientes apresentaram 4,8% de necrose parcial e 2,4% de necrose total do mamilo. Conclusão Em um longo período de acompanhamento desde a primeira cirurgia, foram observadas baixas taxas de complicação pós-operatória e boa sobrevida, porém, associadas comuma alta taxa de recorrência local em pacientes submetidas a NSM para tratamento de recidiva local após cirurgia conservadora. Neste estudo, demonstrou-se que a NSM pode ser considerada uma opção cirúrgica para pacientes que não querem se submeter a mastectomia total.

Nipple-sparing Mastectomy with Immediate Implant-based Reconstruction for Patients with Pure Ductal Carcinoma in Situ / Mastectomia preservadora demamilo com reconstrução imediata baseada em implante para pacientes com carcinoma ductal puro in situ

Abstract Objective The presence of an extensive intraductal component is associated to an increasing risk of relapse in the nipple-areola complex. The aim of the present study was to evaluate the outcomes of patients diagnosed with ductal carcinoma in situ (DCIS) who underwent nipple-sparing mastectomy (NSM) with immediate breast reconstruction using silicone implants. Methods We retrospectively analyzed the postoperative complications and oncological safety of 67 breast cancer patients diagnosed with pure DCIS who underwent NSM with immediate breast reconstruction using silicone implants between 2004 and 2018. Results Among the 127 NSM procedures performed, 2 hematomas (1.5%) and 1 partial nipple necrosis (0.7%) were observed. After a mean follow-up of 60months, the local recurrence rate was of 8.9%, the disease-free survival rate was of 90%, and 1 of the patients died. Conclusion Despite the local recurrence rate, we showed that NSM with immediate breast reconstruction using silicone implants is a feasible surgical approach, with a low rate of complications and high survival rates for patients with a diagnosis of pure DCIS when breast-conserving surgery is not an option.

Resumo Objetivo A presença de componente intraductal extenso é associada ao risco aumentado de recorrência no complexo aréolo-mamilar. O objetivo deste estudo foi avaliar os resultados de pacientes diagnosticados com carcinoma ductal in situ (CDIS)submetidas a adenomastectomia (nipple-sparing mastectomy, NSM, em inglês) com reconstrução mamária imediata utilizando prótese de silicone. Métodos Restrospectivamente, foramanalisadas as complicações pós-operatórias e a segurança oncológica de 67 pacientes com câncer de mama diagnosticadas com CDIS puro, e submetidas a NSM com reconstrução mamária imediata utilizando prótese de silicone, entre 2004 e 2018. Resultados Entre os 127 procedimentos realizados, 2 hematomas (1,5%) e 1 necrose parcial de mamilo (0,7%) foram observados. Após um período médio de 60 meses de seguimento, a taxa de recorrência local foi de 8,9%, a sobrevida livre de doença, de 90%, e apenas 1 paciente foi a óbito. Conclusão Apesar da taxa de recorrência local, demostrou-se que NSM com reconstrução mamária imediata comprótese de silicone é umprocedimento viável, combaixa taxa de complicação e alta sobrevida para pacientes com diagnóstico de CDIS puro quando a cirurgia conservadora da mama não é uma opção.

Salvage Nipple-sparing Mastectomy for Patients with Breast Cancer Recurrence: A Case Series of Brazilian Patients.

OBJECTIVE: Few studies analyzed the safety of salvage nipple-sparing mastectomy (NSM) for local relapse treatment. We evaluated the outcomes of patients with indications for mastectomy who chose to undergo NSM for ipsilateral breast tumor recurrence (IBTR). METHODS: Between January 2001 and December 2018, we evaluated 24 women who underwent NSM for local relapse after conservative surgery. RESULTS: The patients were followed up for a mean time of 132 months since the first surgery. After the NSM, 5 (20.8%) patients were diagnosed with local recurrence and only 1 (4.2%) patient died. The patients presented 4.8% (2) of partial and 2.4% (1) of total nipple necrosis. CONCLUSION: In this long-term follow-up since the first surgery, we observed low rates of complication and good survival, although associated with high local recurrence in patients diagnosed with IBTR undergoing NSM as salvage surgery. We demonstrated that NSM may be considered after IBTR for patients who did not want to undergo total mastectomy.

OBJETIVO: Há poucos estudos sobre a segurança de se realizar adenomastectomia (nipple-sparing mastectomy, NSM, em inglês) para tratamento de recidiva local. O objetivo deste estudo foi avaliar os resultados de pacientes com indicação para mastectomia que optaram por se submeter a NSM para o tratamento de recorrência local. MéTODOS: Foram analisadas 24 pacientes submetidas a NSM para tratamento de recidiva local após tratamento conservador entre janeiro de 2001 e dezembro de 2018. RESULTADOS: As pacientes foram acompanhadas por um período médio de 132 meses a partir da primeira cirurgia. Após a NSM, 5 (20,8%) pacientes foram diagnosticadas com recorrência local, e apenas 1 paciente foi a óbito. As pacientes apresentaram 4,8% de necrose parcial e 2,4% de necrose total do mamilo. CONCLUSãO: Em um longo período de acompanhamento desde a primeira cirurgia, foram observadas baixas taxas de complicação pós-operatória e boa sobrevida, porém, associadas com uma alta taxa de recorrência local em pacientes submetidas a NSM para tratamento de recidiva local após cirurgia conservadora. Neste estudo, demonstrou-se que a NSM pode ser considerada uma opção cirúrgica para pacientes que não querem se submeter a mastectomia total.

Sentinel lymph node biopsy using single-agent mapping tracer (blue dye) after neoadjuvant chemotherapy in a Brazilian cohort of breast cancer patients. Real world evidence.

PURPOSE: To reduce false-negative rates (FNR) in sentinel lymph node biopsy (SLNB) of clinically positive (cN+) axilla in patients undergoing neoadjuvant chemotherapy (NAC). The removal of three or more lymph nodes with dual-tracer mapping including a radioisotope was used. However, in the Brazilian Unified Health System, the radioisotope tracer is not feasible in some hospitals. We conducted a cross-sectional study to evaluate the detection rate of sentinel lymph node (SLN) in patients who converted from cN+ to ycN0 after NAC using blue dye as a single-agent mapping tracer. METHODS: During the period of March 2018 to September 2019, 34 patients who underwent NAC with cN+ who converted to ycN0 were enrolled in the study. The SLNB was performed using blue dye as a single-agent mapping followed by axillary lymph node dissection (ALND). RESULTS: The detection rate of sentinel lymph node was of 85.3%, being SLNB not possible for five patients (14.7%), due to fibrosis. The mean number of removed SLN was 2.5. CONCLUSIONS: The use of blue dye as a single-agent mapping tracer demonstrated an acceptable detection rate of 85.3%. Although the FNR was possible to be determined, the small sample size might overestimate this rate. The removal of three or more lymph nodes with single-agent mapping tracer might be indicated for breast cancer patients who converted to ycN0 after NAC in the Brazilian health public services, in which radioisotope tracer is not suitable.

Sentinel lymph node biopsy using single-agent mapping tracer (blue dye) after neoadjuvant chemotherapy in a Brazilian cohort of breast cancer patients. Real world evidence

ABSTRACT Purpose To reduce false-negative rates (FNR) in sentinel lymph node biopsy (SLNB) of clinically positive (cN+) axilla in patients undergoing neoadjuvant chemotherapy (NAC). The removal of three or more lymph nodes with dual-tracer mapping including a radioisotope was used. However, in the Brazilian Unified Health System, the radioisotope tracer is not feasible in some hospitals. We conducted a cross-sectional study to evaluate the detection rate of sentinel lymph node (SLN) in patients who converted from cN+ to ycN0 after NAC using blue dye as a single-agent mapping tracer. Methods During the period of March 2018 to September 2019, 34 patients who underwent NAC with cN+ who converted to ycN0 were enrolled in the study. The SLNB was performed using blue dye as a single-agent mapping followed by axillary lymph node dissection (ALND). Results The detection rate of sentinel lymph node was of 85.3%, being SLNB not possible for five patients (14.7%), due to fibrosis. The mean number of removed SLN was 2.5. Conclusions The use of blue dye as a single-agent mapping tracer demonstrated an acceptable detection rate of 85.3%. Although the FNR was possible to be determined, the small sample size might overestimate this rate. The removal of three or more lymph nodes with single-agent mapping tracer might be indicated for breast cancer patients who converted to ycN0 after NAC in the Brazilian health public services, in which radioisotope tracer is not suitable.

Axillary management for patients with breast cancer after neoadjuvant chemotherapy: Results of a survey among Brazilian breast surgeons.

BACKGROUND: Currently, there are broadly differing patterns in the management of the axilla after neoadjuvant chemotherapy (NAC) and no consensus with clinically strong evidence on the subject. A survey was performed to assess the current axillary management after NAC among Brazilian breast cancer surgeons. METHODS: The Brazilian Society of Mastology members were invited by email to complete an anonymous online survey and a total of 426 responses were collected. RESULTS: The majority of responders (67%) indicated performing routine axillary staging by physical exam, ultrasound, and fine needle biopsy in case of a suspicious node before NAC. Among breast surgeons working in the Brazilian Public Unified Health System, 11.3% answered that sentinel lymph node biopsy (SLNB) is not reasonable after NAC in their services. Seventy-seven responders (18.2%) reported performing SLNB instead of axillary lymph node dissection (ALND) only in patients who are clinically node-negative before NAC. Axillary complete pathologic response is necessary to omit ALND for 42.8% of responders. The molecular profile of a breast tumor is not considered when choosing axillary management after NAC for 73.7% of responders. CONCLUSIONS: Our survey highlighted the trend towards de-escalation of axillary surgery and observed high heterogeneity in axillary management after chemotherapy in a group of brazilian breast surgeons.

Risk-reducing mastectomy: a case series of 124 procedures in Brazilian patients.

PURPOSE: Women with mutations in breast cancer predisposition genes have a significantly higher lifetime risk of developing breast cancer and can opt for risk-reducing mastectomy. Women with positive family history of cancer can also opt for prophylactic surgery as a preventive method in selected cases. Current studies showed reduced risk of developing breast cancer after prophylactic nipple-sparing mastectomy, however, despite the good clinical outcomes, one of the main concerns regarding nipple-sparing mastectomy (NSM) is the oncological safety of nipple-areola complex preservation. In this study, we aimed to evaluate the indications, complication rates, and unfavorable events of 62 Brazilian patients that underwent risk-reducing NSM from 2004 to 2018. METHODS: Patient data were reviewed retrospectively and descriptive statistics were utilized to summarize the findings. RESULTS: The mean patients age was 43.8 years. The main indication for risk-reducing NSM was the presence of pathogenic mutation (53.3%), followed by atypia or lobular carcinoma in situ (25.8), and family history of breast cancer and/or ovarian cancer (20.9%). There were four (3.2%) incidental diagnosis of ductal carcinoma in situ and one invasive ductal carcinoma (0.8%). From the 124 prophylactic NSM performed, two (1.6%) complications had occurred: one (0.8%) infection and one (0.8%) partial nipple necrosis. In a mean follow-up of 50 months, there was one (1.6%) newly diagnosed breast cancer in the 62 patients undergoing prophylactic NSM. CONCLUSIONS: Our findings demonstrated efficacy and safety to perform NSM as prophylactic surgery with good oncological outcomes and low complication rates in a case series of Brazilian patients.

Effect of intraoperative radiotherapy for early breast cancer on 10-year recurrence rates and overall survival.

The aim of this study was to evaluate 10-year local control and overall survival of IORT for early breast cancer treatment. We analyzed 68 patients submitted to breast conservative surgery and IORT, in the accelerator room of the Radiotherapy Service in South Brazil. In the long-term follow-up, we had 17.6% of patients with ipsilateral breast cancer recurrence, 2.9% with regional recurrence, 2.9% with contralateral breast recurrence, and 5.9% with distant metastasis. The 10-year overall survival was 82.8%. Our data show high local recurrence rates, however, good overall survival in early breast cancer patients treated with breast-conserving surgery and intraoperative radiotherapy with electron beams in the long-term follow-up.

AESTHETIC OUTCOME AND ONCOLOGICAL SAFETY OF NIPPLE-SPARING MASTECTOMY / Resultado estético e segurança oncológica da mastectomia poupadora do mamilo

Background: Nipple-sparing mastectomy (NSM) has been performed for breast cancer treatment and for women at high risk. NSM provides better aesthetic outcomes; however, its oncological safety is still controversial. Objective: To evaluate the surgical complications, oncological safety and aesthetic satisfaction of breast cancer patients undergoing NSM with immediate breast reconstruction operated by the same medical team in a Breast Cancer Center in Brazil. Method: From 2004 to 2011, an aesthetic satisfaction questionnaire was administered to women undergoing NSM followed by immediate breast reconstruction 30 or 60 days after surgery. Aesthetic satisfaction, complication rates and oncological safety were analyzed. Results: Thirty-six breast cancer patients who underwent NSMs followed by immediate reconstruction answered the questionnaire. Most of them considered their results good (51%) or great (43%) and all patients will recommend NSM as a therapeutic treatment for other women with breast cancer. Only one patient presented infection and loss of the mammary implant, and recurrence rates were satisfactory (5.5%). Conclusion: Our findings showed low complication rate, oncological safety and good aesthetic outcome related to NSM with immediate reconstruction in patients from a Breast Cancer Center in Brazil. Despite the limitations of our study, we support the use of NSM with immediate reconstruction for a better aesthetic outcome with oncological safety.

Introdução: A Mastectomia Poupadora do Mamilo (MPM)tem sido realizada em tratamentos de câncer de mama e em mulheres em situação de risco. A cirurgia traz melhores resultados estéticos; todavia, a sua segurança oncológica ainda é controversa. Objetivo: Avaliar as complicações cirúrgicas, a segurança oncológica e a satisfação estética de pacientes com câncer de mama submetendose à MPM com reconstrução imediata da mama operadas pela mesma equipe médica em um centro de câncer de mama no Brasil. Método: De 2004 a 2011, um questionário de satisfação estética foi administrado a mulheres submetidas à MPM seguida de reconstrução imediata de mama 30 ou 60 dias após a cirurgia. Foram analisadas a satisfação estética, as taxas de complicações e a segurança oncológica. Resultados: Trinta e seis pacientes com câncer que se submeteram a MPMs seguidas de reconstrução imediata responderam ao questionário. A sua maioria considerou os resultados bons (51%) ou ótimos (43%) e todos os pacientes a recomendarão como tratamento terapêutico a outras mulheres com câncer de mama. Apenas uma paciente apresentou infecção e perda do implante mamário, e as taxas de recorrência foram satisfatórias (5,5%). Conclusão: Nossas descobertas mostraram baixa taxa de complicação, segurança oncológica e bom resultado estético relacionado à MPM com reconstrução imediata em pacientes de um centro de câncer de mama no Brasil. Apesar das limitações do nosso estudo, nós apoiamos o uso da MPM com reconstrução imediata para um melhor resultado estético com segurança oncológica.

The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

Administration of a Histone Deacetylase Inhibitor into the Basolateral Amygdala Enhances Memory Consolidation, Delays Extinction, and Increases Hippocampal BDNF Levels.

Gene expression related to the formation and modification of memories is regulated epigenetically by chromatin remodeling through histone acetylation. Memory formation and extinction can be enhanced by treatment with inhibitors of histone deacetylases (HDACs). The basolateral amygdala (BLA) is a brain area critically involved in regulating memory for inhibitory avoidance (IA). However, previous studies have not examined the effects of HDAC inhibition in the amygdala on memory for IA. Here we show that infusion of an HDAC inhibitor (HDACi), trichostatin A (TSA), into the BLA, enhanced consolidation of IA memory in rats when given at 1.5, 3, or 6 h posttraining, but not when the drug was infused immediately after training. In addition, intra-BLA administration of TSA immediately after retrieval delayed extinction learning. Moreover, we show that intra-BLA TSA in rats given IA training increased the levels of brain-derived neurotrophic factor in the dorsal hippocampus, but not in the BLA itself. These findings reveal novel aspects of the regulation of fear memory by epigenetic mechanisms in the amygdala.

Histone deacetylase inhibition prevents the impairing effects of hippocampal gastrin-releasing peptide receptor antagonism on memory consolidation and extinction.

Hippocampal gastrin-releasing peptide receptors (GRPR) regulate memory formation and extinction, and disturbances in GRPR signaling may contribute to cognitive impairment associated with neurodevelopmental disorders. Histone acetylation is an important epigenetic mechanism that regulates gene expression involved in memory formation, and histone deacetylase inhibitors (HDACis) rescue memory deficits in several models. The present study determined whether inhibiting histone deacetylation would prevent memory impairments produced by GRPR blockade in the hippocampus. Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or the HDACi sodium butyrate (NaB) shortly before inhibitory avoidance (IA) training, followed by an infusion of either SAL or the selective GRPR antagonist RC-3095 immediately after training. In a second experiment, the infusions were administered before and after a retention test trial that served as extinction training. As expected, RC-3095 significantly impaired consolidation and extinction of IA memory. More importantly, pretraining administration of NaB, at a dose that had no effect when given alone, prevented the effects of RC-3095. In addition, the combination of NaB and RC-3095 increased hippocampal levels of the brain-derived neurotrophic factor (BDNF). These findings indicate that HDAC inhibition can protect against memory impairment caused by GRPR blockade.

TrkB blockade in the hippocampus after training or retrieval impairs memory: protection from consolidation impairment by histone deacetylase inhibition.

Relatively little is known about the requirement of signaling initiated by brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), in the early phases of memory consolidation, as well as about its possible functional interactions with epigenetic mechanisms. Here we show that blocking TrkB in the dorsal hippocampus after learning or retrieval impairs retention of memory for inhibitory avoidance (IA). More importantly, the impairing effect of TrkB antagonism on consolidation was completely prevented by the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB). Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or NaB before training, followed by an infusion of either vehicle (VEH) or the selective TrkB antagonist ANA-12 immediately after training. In a second experiment, the infusions were administered before and after retrieval. ANA-12 after either training or retrieval produced a significant impairment in a subsequent memory retention test. Pretraining administration of NaB prevented the effect of ANA-12, although NaB given before retrieval did not alter the impairment resulting from TrkB blockade. The results indicate that inhibition of BDNF/TrkB in the hippocampus can hinder consolidation and reconsolidation of IA memory. However, TrkB activity is not required for consolidation in the presence of NaB, suggesting that a dysfunction in BDNF/TrkB signaling can be fully compensated by HDAC inhibition to allow hippocampal memory formation.