Could be FOXO3a, miR-96-5p and miR-182-5p useful for Brazilian women with luminal A and triple negative breast cancers prognosis and target therapy?

Abstract FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. Their potential prognostic role for the patients was also evaluated. We identified the miRNAs miR-96-5p and miR-182-5p, de-scribed as negative regulators of FOXO3A, with differential expression both in LA and TN tumors when compared to normal tissue. The miR-96-5p and miR-182-5p miRNAs were upregulated in LA (7.82 times, p < 0.005; 6.12 times, p < 0.005, respectively) and TN breast cancer samples (9.42 times, p < 0.0001; 8.51 times, p < 0.0001) compared to normal tissues. The samples with higher miR-96-5p and miR-182-5p expression (FR ≥ 4) were submitted for FOXO3a immunostaining. Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs.

When to indicate radiotherapy after nipple-sparing mastectomy? Systematic review / Quando indicar radioterapia após mastectomia nipple-sparing? Revisão sistemática

Introduction: Nipple-sparing mastectomy (NSM) and preservation of the nipple-areola complex (NAC) represent a therapeutic option of breast cancer with a better aesthetic result, a positive impact on body image and more satisfaction than the reconstruction of the NAC. It is questioned the indication of radiotherapy when the NAC is maintained and its potential aesthetic impairment. Objective: To examine the indication of radiotherapy in NSM and, secondarily, the incidence of NAC involvement and local recurrence rates. Methods: Systematic review carried out in the PubMed database with the terms ("breast neoplasm" [Mesh] OR "breast cancer") AND ("radiotherapy" OR "radiation therapy") AND ("nipple sparing mastectomy" OR "mastectomies" OR "subcutaneous mastectomies"). The selection of the studies, the evaluation of its quality and data extraction were carried out independently by four reviewers. Results: The indications for radiotherapy after NSM were: positive axilla, tumors over 5 cm and retroareolar tissue remaining greater than 5 mm. The NAC involvement occurred in 5 to 26.1% in the definitive anatomopathological study. NAC recurrence occurred from 2.59 to 10%. NAC necrosis occurred in 2.2 to 43.4%. Conclusions: The radiotherapy indications for NSM seem to follow the same classical indications for radiotherapy after mastectomy. The relapse index in NAC was not shown to be larger and without difference for the type of radiotherapy used. Radiotherapy should be based on factors that suggest a high risk for NAC involvement

Introdução: A mastectomia nipple-sparing (MNS) e a conservação do complexo aréolo-papilar (CAP) representam uma manobra terapêutica do câncer de mama com melhor resultado estético, impacto positivo na imagem corporal e mais satisfação do que a reconstrução do CAP. Questiona-se a indicação de radioterapia quando da manutenção do CAP e seu potencial prejuízo estético. Objetivo: Examinar a indicação de radioterapia em MNS e, secundariamente, a incidência do envolvimento do CAP e as taxas de recorrência local. Métodos: Revisão sistemática realizada na base de dados do PubMed com os termos ("breast neoplasm" [Mesh] OR "breast cancer") AND ("radiotherapy" OR "radiation therapy") AND ("nipple sparing mastectomy" OR "mastectomies" OR "subcutaneous mastectomies"). A seleção dos estudos, a avaliação da qualidade do estudo e a extração de dados foram realizadas de forma independente por quatro revisores. Resultados: As indicações para radioterapia após MNS foram: axila positiva, tumores acima de 5 cm e tecido retroareolar remanescente maior que 5 mm. O envolvimento do CAP ocorreu em 5 a 26,1% no anatomopatológico definitivo. A recorrência no CAP ocorreu de 2,59 a 10%. A necrose do CAP ocorreu em 2,2 a 43,4%. Conclusão: As indicações de radioterapia para MNS parecem seguir as mesmas indicações clássicas para radioterapia após mastectomia. O índice de recidiva no CAP não mostrou ser maior com uso de radioterapia nem ter diferença quanto ao seu tipo. A decisão de realizar a radioterapia deve se basear em fatores que sugerem alto risco para envolvimento do CAP

Analysis of the concordance rates between core needle biopsy and surgical excision in patients with breast cancer / Análise das taxas de concordância entre a biópsia com agulha grossa e a excisão cirúrgica em pacientes com câncer de mama

OBJECTIVE: To evaluate whether immunohistochemical marker studies performed on core needle biopsy (CNB) specimens accurately reflect the marker status of the tumor obtained from final surgical specimen. METHODS: This was a retrospective study that used the database of the Division of Mastology of the Hospital das Clínicas, São Paulo, Brazil. Sixty-nine patients submitted to ultrasound-guided CNB diagnosed with breast cancer were retrospectively analyzed. Immunohistochemistry (IHC) on core biopsy specimens was compared to that of excisional biopsy regarding estrogen receptor (ER), progesterone receptor (PR), human epidermal gowth factor receptor 2 gene (HER2), p53, and Ki67. The analysis of the concordance between CNB and surgical biopsy was performed using the kappa (k) coefficient (95% CI). RESULTS: A perfect concordance between the labeling in the surgical specimens and the preoperative biopsies in p53 (k = 1.0; 95% CI: 0.76-1.0) was identified. There was an almost perfect concordance for ER (k = 0.89; 95% CI: 0.65-1.0) and a substantial concordance for PR (k = 0.70; 95% CI: 0.46-0.93). HER2 (k = 0.61; 95% CI: 0.38-0.84) and Ki-67 (k = 0.74; 95% CI: 0.58-0.98) obtained a substantial concordance this analysis. CONCLUSION: The results of this study indicate that the immunohistochemical analysis of ER, PR, Ki-67, and p53 from core biopsy specimens provided results that accurately reflect the marker status of the tumor. The concordance rate of HER2 was less consistent; although it produced substantial concordance, values were very close to moderate concordance.

OBJETIVO: Avaliar se a análise dos marcadores imunoistoquímicos obtidos por meio de espécimes de core biopsy (CB) refletem com precisão o perfil dos marcadores tumorais obtidos por biópsia cirúrgica excisional (BCE). MÉTODOS: Estudo retrospectivo usando dados da Divisão de Mastologia do Hospital das Clínicas de São Paulo. Sessenta e nove pacientes submetidas à CB guiada por ultrassom com diagnóstico de câncer de mama foram analisadas retrospectivamente. O exame imunoistoquímico dos espécimes de CB foram comparados com aquele obtido a partir da BCE em relação ao receptor de estrogênio (RE), receptor de progesterona (RP), human epidermal gowth factor receptor 2 gene (HER2), p53 e Ki-67. A análise de concordância entre a CB e a BCE foram realizados usando o coeficiente de kappa (k) (IC 95%). RESULTADOS: A concordância perfeita entre a BCE e a CB do p53 (k = 1,0; IC 95%: 0,76-1,0) foi identificada. A concordância foi quase perfeita para o RE (k = 0,89; IC 95%: 0,65-1,0) e concordância substancial foi identificada para o RP (= 0,70; IC 95%: 0,46-0,93). O HER2 (k = 0,61; IC 95%: 0,38-0,84) e Ki-67 (k = 0,74; IC 95%: 0,58-0,98) obtiveram uma concordância substancial nesta análise. CONCLUSÃO: os resultados deste estudo indicam que a análise imunoistoquímica do RE, RP, Ki-67 e p53 a partir dos espécimes de CB fornecem resultados que refletem com precisão o perfil dos marcadores do tumor. O HER2 foi menos consistente, porque apesar de ter produzido uma concordância substancial, os valores foram muito próximos da concordância moderada.