Abstract Objective Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with triple-negative breast cancer (TNBC) with tumors > 1 cm or positive axillary nodes. Pathologic complete response (pCR) has been used as an endpoint to select patients for treatment scaling. This study aimed to examine the benefit of adding adjuvant capecitabine for TNBC patients who did not achieve pCR after standard NACT in a real-world scenario. Methods This retrospective cohort study included all patients with TNBC who underwent NACT between 2010 and 2020. Clinicopathological data were obtained from the patient records. Univariate and multivariate analyses were conducted at the 5 years follow-up period. Results We included 153 patients, more than half of whom had stage III (58.2%) and high-grade tumors (60.8%). The overall pCR rate was 34.6%, and 41% of the patients with residual disease received adjuvant capecitabine. Disease-specific survival (DSS) among the patients who achieved pCR was significantly higher (p<0.0001). Residual disease after NACT was associated with detrimental effects on DSS. In this cohort, we did not observe any survival benefit of adding adjuvant capecitabine for patients with TNBC subjected to NACT who did not achieve pCR (p=0.52). Conclusion Our study failed to demonstrate a survival benefit of extended capecitabine therapy in patients with TNBC with residual disease after NACT. More studies are warranted to better understand the indication of systemic treatment escalation in this scenario. (NACT triplenegative triple negative (TNBC nodes (pCR scaling realworld real world scenario 201 2020 records followup follow up period 15 58.2% 582 58 2 (58.2% highgrade high grade 60.8%. 608 60.8% . 60 8 (60.8%) 346 34 6 34.6% 41 Diseasespecific Disease specific DSS (DSS p<0.0001. p00001 p p<0.0001 0 0001 (p<0.0001) p=0.52. p052 p=0.52 52 (p=0.52) 20 202 58.2 (58.2 60.8 (60.8% 3 34.6 4 p0000 p<0.000 000 (p<0.0001 p05 p=0.5 (p=0.52 58. (58. 60. (60.8 34. p000 p<0.00 00 (p<0.000 p0 p=0. (p=0.5 (58 (60. p00 p<0.0 (p<0.00 p=0 (p=0. (5 (60 p<0. (p<0.0 p= (p=0 ( (6 p<0 (p<0. (p= p< (p<0 (p (p<

Abstract Objective Although autologous bone grafting is the most widely used treatment for bone defects, the most effective preparation remains unclear. This animal study aimed to compare different autologous bone grafting preparation for the treatment of rats calvaria critical bone defect. Methods 122 rats were randomly allocated into three groups: Simulado, Macerated and Chopped. The specimens underwent craniotomies at the top center of their calvarias with a 7mm diameter circumferential cutter drill. The critical bone defect produced was treated or not according to the group the specimen wasallocated. The rats were euthanized at 3, 6 or 12 weeks post-op and its calvarias were analyzed by histomorphometry, bone densitometry, nanocomputed tomography (nCT), and biomechanical tests. Results The histomorphometry analysis showed the highest percentage of fulfillment of the critical bone defect in the chopped and macerated group when compared to simulado. The densitometry assessment evidenced higher bone mass at all endpoints analysis (p < 0.05) in the chopped group. The nCT data exhibited an expressive increase of bone in the chopped group when compared with the simulado and macerated groups. The biomechanical tests exhibited highest values of deformation, maximum force, and relative stiffness in the chopped group at any time of euthanasia (p < 0.05). Conclusions Our experimental work showed that chopped bone grafting preparation exhibited significant better outcomes than macerated in the treatment of a critical bone defect in rats calvaria. defects unclear groups Simulado Chopped mm drill wasallocated 3 1 postop post op nCT, , (nCT) p 0.05 005 0 05 deformation force 0.05. . (nCT 0.0 00 0.

Resumo Objetivo Embora enxertos ósseos autólogos sejam o tratamento mais utilizado para defeitos ósseos, a preparação mais eficaz ainda é obscura. Este estudo animal teve como objetivo comparar diferentes preparações de enxerto ósseo autólogo para o tratamento de defeito ósseo crítico no crânio de ratos. Métodos No total, 122 ratos foram alocados aleatoriamente em três grupos: Simulado, enxerto macerado e enxerto picado. Os espécimes foram submetidos a craniotomias no centro superior do crânio com broca de corte circunferencial de 7 mm de diâmetro. O defeito ósseo crítico produzido foi tratado ou não de acordo com o grupo de alocação do animal. Os ratos foram eutanasiados às 3, 6 ou 12 semanas após a cirurgia e seus crânios foram analisados por histomorfometria, densitometria óssea, nanotomografia computadorizada (nTC) e testes biomecânicos. Resultados A análise histomorfométrica mostrou maior percentual de preenchimento do defeito ósseo crítico no grupo picado e macerado em comparação ao simulado. A avaliação densitométrica evidenciou maior massa óssea em todos os desfechos de análise (p < 0,05) no grupo picado. Os dados de nTC revelaram um aumento ósseo expressivo no grupo picado em comparação aos grupos simulado e macerado. Os testes biomecânicos mostraram maiores valores de deformação, resistência máxima e rigidez relativa no grupo picado em qualquer momento da eutanásia (p < 0,05). Conclusões Nosso estudo mostrou que a preparação de enxerto ósseo picado gerou resultados significativamente melhores do que os enxertos macerados no tratamento de defeitos ósseos críticos no crânio de ratos. obscura total Simulado diâmetro 3 1 histomorfometria (nTC p 0,05 005 0 05 deformação 0,05. . 0,0 00 0,

Abstract Objectives The COVID-19 pandemic has had a significant global impact since its declaration in March 2020. The COVID-19 pandemic has disproportionately impacted cancer patients, particularly those with breast cancer. This study aims to analyze the effects of the pandemic on women diagnosed with breast cancer recurrence. Methods A cohort study was conducted at a tertiary public hospital in São Paulo State, Brazil. Data were collected from electronic records. Patients diagnosed with breast cancer and experiencing recurrence between January 2011 and March 2022 were included. Survival analysis was performed using the Kaplan-Meier estimator and Cox regression. Results The study included 187 patients, 45 in the pandemic group (recurrence after March 23, 2020) and 142 in the pre-pandemic group. Distant recurrences were more frequent in both groups (pre-pandemic: 62.7 %, pandemic: 75.5 %). Compared to the pre-pandemic group (1.8 years), the pandemic group experienced a longer mean time to recurrence detection (2.9 years) and significantly decreased median survival (9 months vs. 22 months). The Cox regression analysis confirmed an increased risk of death for women diagnosed with breast cancer recurrence during the pandemic period (HR = 1.92, 95 % CI 1.19‒3.12). Conclusion The present study is among the first to investigate the pandemic's specific effects on breast cancer recurrence, revealing concerning delays in detection and a decrease in survival rates. Prompt diagnosis, timely treatment initiation, and comprehensive support are crucial during public health crises. These findings urge healthcare systems to prioritize tailored care for breast cancer patients during pandemics. COVID19 COVID 19 COVID-1 2020 State Brazil records 201 202 KaplanMeier Kaplan Meier 18 4 23 14 prepandemic pre (pre-pandemic 627 62 7 62. 755 75 5 75. %. . %) 1.8 1 8 (1. years, years , 2.9 29 2 9 (2. ( vs months. months) HR 192 92 1.92 1.19‒3.12. 119312 1.19‒3.12 3 12 1.19‒3.12) pandemics s rates diagnosis initiation crises COVID1 COVID- 20 6 1. (1 2. (2 1.9 11931 1.19‒3.1 1193 1.19‒3. 119 1.19‒3 11 1.19‒ 1.19 1.1

SUMMARY OBJECTIVE: A surgery is essential for the management of early endometrial carcinoma. Due to the comorbidities associated with the disease, the complications of surgery are common. Laparoscopic surgery may reduce surgical complications but also have oncological risks. We aimed to compare recurrence and overall survival (OS) associated with laparoscopy and laparotomy for early endometrial cancer. METHODS: We included women treated for presumed early endometrial carcinoma at the Clinics Hospital of Ribeirão Preto Medical School from January 1998 to December 2017. We designed a 1:2 propensity score-matched case-control and compared the patients’ characteristics, short-term outcomes, recurrence, and OS. RESULTS: A total of 252 women were included in this study, 168 underwent laparotomy, and 84 underwent laparoscopy. The two groups were well balanced according to most of the variables, and obesity was a characteristic of patients in both groups. Laparoscopy was associated with increased surgical time (194.7 min vesus 165.6 min; p<0.001) and reduced rate of surgical complications (6.5% versus 0; p=0.038). Laparoscopic surgery was not associated with the risk of tumor recurrence (HR: 0.41, 95%CI 0.14-1.19, p=0.100) or all-cause mortality (HR: 0.49, 95%CI 0.18-1.35, p=0.170). CONCLUSION: Laparoscopy was safe in terms of oncological outcomes and was associated with a lower rate of surgical complications. Our data support the use of minimally invasive surgery as the preferential approach in the management of early endometrial carcinoma.

Resumo Objetivo O uso de marcadores moleculares pode identificar subtipos tumorais com diferentes taxas de recidiva. O objetivo do presente estudo é caracterizar a expressão imunohistoquímica da vimentina (VIM), da E-caderina (CDH1) e de CK5 em pacientes com carcinoma ductal invasivo (CDI) da mama. Métodos Utilizamos uma matriz de amostras teciduais (TMA, na sigla em inglês) de 87 pacientes com CDI da mama. Para avaliar a expressão dos receptores de estrogênio (RE) e receptores de progesterona (RP), HER2, VIM, CDH1, CK5 e Ki67, utilizamos imunohistoquímica. Os tumores foram classificados como luminal A e B (n = 39), HER2+ (n = 25) e triplo negativo (TNBC) (n = 23). Resultados Foi observado que tumores luminais A e B não expressaram o fenótipo VIM+/CDH1-/low. Este fenótipo foi observado em 16,5% dos tumores HER2+ e em 60% dos tumores TNBC (p = 0,0001). Dos 20 tumores TNBC, a CK5 (marcador de tumor basalóide) foi super expressa em 11 amostras. O fenótipo VIM+/CDH1-/low foi observado em 5 tumores CK5+ TNBC (45%) e em 7 dos 9 tumores CK5- TNBC (78%) (p = 0,02). A expressão média de Ki67 nos tumores VIM+/CDH1-/low foi 13.6 (amplitude de 17,8 a 45,4) comparado com 9,8 (amplitude de 4,1 a 38,1) nos outros tumores (p = 0,0007). A presença demetástase linfonodal foimenor em tumores com fenótipo VIM+/CDH1-/low (23% contra 61%; teste X2; p = 0,01). Conclusão Nossos achados sugerem que a expressão de VIM e CDH1 pode identificar um subtipo de CDI da mama com fenótipo mesenquimal associado a pior prognóstico, lesões de alto grau e alto índice mitótico.

Abstract Objective The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs). Methods We have constructed a tissuemicroarray (TMA) from87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B (n = 39), HER2 enriched (n = 25), and triple-negative (TNBC) (n = 23), based on the IHC expression. Results We have observed that luminal A and B tumors lack the VIM+/CDH1-/low phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors (p = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM+/CDH1-/low phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) (p = 0.02). The median Ki67 index in the VIM+/CDH1-/low tumors was 13.6 (range: 17.8-45.4) compared with 9.8 (range: 4.1-38.1) in other tumors (p = 0.0007). The presence of lymph nodemetastasis was less frequent in patients with VIM+/CDH1-/low tumors (23% versus 61%; X2 test; p = 0.01). Conclusion Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index.

O objetivo deste artigo é descrever os aspectos de imagem mais característicos do carcinoma mucinoso de mama, destacando-se os padrões relacionados a melhor prognóstico. Foram selecionados casos de carcinoma mucinoso de mama enfatizando as características de imagem que sugiram esse subtipo de neoplasia mamária, seja na mamografia, ultrassonografia ou ressonância magnética.

The present essay is aimed at describing the most characteristic imaging findings of mucinous carcinoma of the breast, with emphasis on the patterns related to better prognosis. The authors selected cases of mucinous carcinoma of the breast whose images were available, highlighting the imaging findings suggestive of this subtype of breast cancer, either at mammography, ultrasonography or magnetic resonance imaging.

OBJETIVO: Foi determinar se a avaliação clínica é adequada na determinação do volume a ser ressecado em cirurgias conservadoras de mama após tratamento neoadjuvante. MÉTODOS: Avaliamos 279 pacientes com diagnóstico histológico de carcinoma invasor de mama submetidas à terapia neoadjuvante seguida de tratamento cirúrgico ou tratadas com cirurgia primária. O volume de tecido excisado, o volume da massa tumoral e o volume ótimo para a excissão cirúrgica baseado em uma margem de 1 cm foram calculados. O excesso de volume excisado foi estimado pelo cálculo da taxa de ressecção determinada pelo volume de tecido excisado dividido pelo volume ótimo para a excisão cirúrgica. Analisamos a extensão da ressecção cirúrgica e o efeito do exesso de tecido ressecado na obtenção de margens cirúrgicas. RESULTADOS: A mediana do diâmetro tumoral foi de 2,0 e 1,5 cm nos grupos de cirurgia primária e terapia neoadjuvante, respectivamente. A mediana do volume de tecido mamário ressecado foi de 64,3 cm³ no grupo de cirurgia primária e de 90,7 cm³ no grupo de tratamento neoadjuvante. A taxa mediana de ressecção nos grupos de cirurgia primária e terapia neoadjuvante foram 2,0 e 3,3 respectivamente (p<0,0001). Os dados relacionados à margem cirúrgica foram similares em ambos os grupos. A comparação do volume de tecido ressecado mostrou correlação positiva no grupo de cirurgia primária, porém não no grupo de tratamento neoadjuvante. CONCLUSÃO: Existe uma tendência dos cirurgiões a removerem maior quantidade de tecido mamário durante cirurgias conservadoras de mama de pacientes que foram submetidas à tratamento neoadjuvante, resultando na perda da correlação entre o diâmetro tumoral e o volume do espécime excisado.

PURPOSE: We aimed to determine whether clinical examination could adequately ascertain the volume of tissue to be resected during breast-conserving surgery after neoadjuvant therapy. METHODS: We reviewed the clinical reports of 279 patients with histologically diagnosed invasive breast carcinomas treated with neoadjuvant therapy followed by surgery or with primary surgery alone. We estimated volumes of excised tissues, the volume of the tumor mass and the optimal volume required for excision based on 1 cm of clear margins. The actual excess of resected volume was estimated by calculating the resection ratio measured as the volume of the resected specimen divided by the optimal specimen volume. The study endpoints were to analyze the extent of tissue resection and to ascertain the effect of excess resected tissue on surgical margins in both groups of patients. RESULTS: The median tumor diameter was 2.0 and 1.5 cm in the surgery and neoadjuvant therapy groups, respectively. The median volume of resected mammary tissue was 64.3 cm³ in the primary surgery group and 90.7 cm³ in the neoadjuvant therapy group. The median resection ratios in the primary surgery and neoadjuvant therapy groups were 2.0 and 3.3, respectively (p<0.0001). Surgical margin data were similar in both groups. Comparison of the volume of resected mammary tissues with the tumor diameters showed a positive correlation in the primary surgery group and no correlation in the neoadjuvant therapy group. CONCLUSION: Surgeons tend to excise large volumes of tissue during breast-conserving surgery after neoadjuvant therapy, thereby resulting in a loss of the correlation between tumor diameter and volume of the excised specimen.

OBJECTIVE: To analyze the expression of hypoxia-inducible factors (hypoxia-inducible factor 1A and hypoxia-inducible factor 2A) and aldehyde dehydrogenase proteins in patients with locally advanced breast carcinoma who were subjected to neoadjuvant chemotherapy. METHODS: We included 90 patients with histologically confirmed stage II and III breast carcinoma who were treated with neoadjuvant chemotherapy between 2000 and 2005. Immunohistochemistry for aldehyde dehydrogenase, hypoxia-inducible factor 1A, and hypoxia-inducible factor 2A was performed before and after neoadjuvant chemotherapy. We analyzed the influence of clinical and pathological features on clinical and pathological response, disease-free survival, and overall survival. RESULTS: An objective clinical response to neoadjuvant chemotherapy was observed in 80% of patients, with 12% showing a complete pathological response. Among all clinical and pathological parameters, only the expression of hypoxia-inducible factor 1A was associated with a pathological response. A positive association was found between expression of aldehyde dehydrogenase and that of hypoxia-inducible factor 1A before and after chemotherapy. Aldehyde dehydrogenase expression was associated with expression of hypoxia inducible-factor 2A in tumors after neoadjuvant treatment. In a univariate analysis, prognosis was influenced by age, pathological response, metastasis to axillary lymph nodes after neoadjuvant chemotherapy, overexpression of hypoxia-inducible factor 2, and the presence of aldehyde dehydrogenase-positive cells within the primary tumor after neoadjuvant chemotherapy. In a multivariate analysis, only age and the presence of aldehyde dehydrogenase-positive cells after chemotherapy were associated with reduced overall survival. CONCLUSION: The presence of aldehyde dehydrogenase-positive cells within the residual tumor after neoadjuvant chemotherapy is associated with an increase in the expression of hypoxia-inducible factor 2A and with poor prognosis in patients with locally advanced breast cancer.

PURPOSE: To develop a mouse model to study the influence of hypoxia in breast cancer progression and metastasis. METHODS: The 4T1 cell line was used to engraft the kidneys of female BALB/c mice. Placing an aneurysm clip on the kidney hilum, hypoxia can be directed to tumor site. Histological evaluation was used to analyze the morphological changes induced by ischemia in kidney cortex, and to verify the metastatic potential. RESULTS: 4T1 cells can be engrafted into the renal cortex and the renal ischemia caused by using a clip to clamp the renal hilum induces hypoxia at the tumor site. This procedure maintains the ability of 4T1 cells to metastasize. In fact, our preliminary results showed that tumor hypoxia precipitates the metastatic dissemination of tumor cells. After 14 days of engraftment, lung metastases were observed only in mice that were subjected to tumor hypoxia. CONCLUSION: This model can help us to understand how low oxygen tension mediates hypoxia-induced proteomic and genomic changes in breast cancer.

Os tumores neuroendócrinos primários de mama (TNPMs) são incomuns e não há consenso quanto a tratamento e prognóstico. No presente trabalho, foram revisados os diagnósticos de 1.184 pacientes com câncer de mama atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP/USP), identificando três casos que preenchiam os critérios de TNPM, segundo classificação estabelecida pela Organização Mundial da Saúde (OMS) em 2003. Foram avaliados os achados clinicopatológicos e imuno-histoquímicos e as terapias realizadas, buscando caracterizar os padrões histopatológicos e de comportamento distintos dos carcinomas convencionais de mama.

Primary neuroendocrine breast carcinomas (NECs) are uncommon. Moreover, there is no consensus as to its treatment and prognosis. In this study, the diagnoses of 1,184 cases of breast cancer treated at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto/Universidade de São Paulo (HCFMRP/USP) were reviewed. Three among them fulfilled the criteria for primary NEC according to the classification established by the World Health Organization (WHO) in 2003. Clinicopathological, immunohistochemical features and treatments were assessed in order to characterize histopathological and distinct patterns of conventional breast carcinomas.

BACKGROUND: Locally advanced breast cancers are more prevalent in underdeveloped countries. Targeted therapy has been improved to identify hallmarks that are specific to these subtypes of tumors. OBJECTIVES: We aimed to prospectively assess the expression of Hypoxia inducible factor-1 α and vascular endothelial growth factor-C in locally advanced breast cancer patients. METHODS: Thirty women underwent incisional biopsies for the histopathological diagnosis of breast carcinoma and participated in neoadjuvant chemotherapy. The association of Hypoxia inducible factor-1 α and vascular endothelial growth factor-C with age, tumor size, histological grade, clinical staging, hormonal and axillary status, clinical and pathological response after neoadjuvant chemotherapy, expression of estrogen and progesterone receptors, and the presence of c-erbB-2 antigen was studied. RESULTS: Hypoxia inducible factor-1 α expression and Vascular endothelial growth factor-C expression were observed in 66.7% and 63.3% of all patients, respectively, and were marginally associated with each other (p = 0.06). Among the studied variables, only positive axillary status was associated with the presence of HIF-1α (p = 0.02). Complete pathological response was significantly associated (p = 0.04) with the expression of vascular endothelial growth factor-C prior to neoadjuvant chemotherapy. CONCLUSION: We concluded that Hypoxia inducible factor-1 α was associated with a poor prognosis and that vascular endothelial growth factor-C could be used as a predictive factor in locally advanced breast cancer patients with complete pathological response after neoadjuvant chemotherapy.