Background: Breast cancer is a heterogeneous disease associated with different patient prognosis and responses to therapy. Vitamin D has been emerging as a potential treatment for cancer, as it has been demonstrated that it modulates proliferation, apoptosis, invasion and metastasis, among others. It acts mostly through the Vitamin D receptor (VDR) and the synthesis and degradation of this hormone are regulated by the enzymes CYP27B1 and CYP24A1, respectively. We aimed to study the expression of these three proteins by immunohistochemistry in a series of breast lesions. Methods: We have used a cohort comprising normal breast, benign mammary lesions, carcinomas in situ and invasive carcinomas and assessed the expression of the VDR, CYP27B1 and CYP24A1 by immunohistochemistry. Results: The results that we have obtained show that all proteins are expressed in the various breast tissues, although at different amounts. The VDR was frequently expressed in benign lesions (93.5%) and its levels of expression were diminished in invasive tumours (56.2%). Additionally, the VDR was strongly associated with the oestrogen receptor positivity in breast carcinomas. CYP27B1 expression is slightly lower in invasive carcinomas (44.6%) than in benign lesions (55.8%). In contrast, CYP24A1 expression was augmented in carcinomas (56.0% in in situ and 53.7% in invasive carcinomas) when compared with that in benign lesions (19.0%). Conclusions: From this study, we conclude that there is a deregulation of the Vitamin D signalling and metabolic pathways in breast cancer, favouring tumour progression. Thus, during mammary malignant transformation, tumour cells lose their ability to synthesize the active form of Vitamin D and respond to VDR-mediated Vitamin D effects, while increasing their ability to degrade this hormone.
Introduction: The expression of additional genes, other than oestrogen receptor (ER), may be important to the hormone-responsive phenotype of breast cancer. Microarray analyses have revealed that forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA-3) are expressed in close association with ERα, both encoding for transcription factors with a potential involvement in the ERα-mediated action in breast cancer. The purpose of this study was to explore if the expression of FOXA1 and GATA-3 may provide an opportunity to stratify subsets of patients that could have better outcome, among the ERα-negative/poor prognosis breast cancer group. Methods: We evaluate FOXA1 and GATA-3 expression in 249 breast carcinomas by immunohistochemistry, associating it with breast cancer molecular markers, clinicopathological features and patient's survival. The clinicopathological features and immunohistochemical markers of the tumours were compared using the chi-square test and ANOVA. Disease-free survival was analysed through Kaplan–Meier survival curves and Cox regression. Results: FOXA1 expression was demonstrated in 42% of invasive carcinomas, while GATA-3 was detected in 48% of the cases. FOXA1 expression was inversely associated with tumour size, Nottingham Prognostic Index, histological grade, lymph vascular invasion, lymph node stage and human epidermal growth factor receptor-2 (HER-2) overexpression, while GATA-3 expression showed inverse association with histological grade and HER-2. Both FOXA1 and GATA-3 were directly associated with ERα and progesterone receptor. Among FOXA1-positive tumours, 83.1% are comprised in the luminal A subtype, similar to GATA-3 where 87.7% of positive tumours were classified within this molecular subtype. In the subset of ERα-negative patients, those who were FOXA1-negative had a 3.61-fold increased risk of breast cancer recurrence when compared with the FOXA1-positive. Conclusions: FOXA1 was a significant predictor of good outcome in breast cancer, whereas GATA-3 was an important luminal marker. The expression of FOXA1 may be used for risk stratification among ERα-negative patients.
A breast cancer prognostic tool should ideally be applicable to all types of invasive breast lesions. A number of studies have shown histopathological grade to be an independent prognostic factor in breast cancer, adding prognostic power to nodal stage and tumour size. The Nottingham Prognostic Index has been shown to accurately predict patient outcome in stratified groups with a follow-up period of 15 years after primary diagnosis of breast cancer. Clinically, breast tumours that lack the expression of Oestrogen Receptor, Progesterone Receptor and Human Epidermal growth factor Receptor 2 (HER2) are identified as presenting a "triple-negative" phenotype or as triple-negative breast cancers. These poor outcome tumours represent an easily recognisable prognostic group of breast cancer with aggressive behaviour that currently lack the benefit of available systemic therapy. There are conflicting results on the prevalence of lymph node metastasis at the time of diagnosis in triple-negative breast cancer patients but it is currently accepted that triple-negative breast cancer does not metastasize to axillary nodes and bones as frequently as the non-triple-negative carcinomas, favouring instead, a preferentially haematogenous spread. Hypothetically, this particular tumour dissemination pattern would impair the reliability of using Nottingham Prognostic Index as a tool for triple-negative breast cancer prognostication.
O complexo processo de envelhecimento, associado a alterações no sistema imunológico, desencadeia um aumento do risco de doenças. Em idosos, instabilidades genéticas com dano ao DNA podem induzir o desenvolvimento de câncer e, consequentemente, uma relação causal com aumento da mortalidade. Este artigo de revisão aborda tópicos sobre condições clínicas preexistentes associadas a um diagnóstico de câncer. Doenças cardiovasculares, depressão, demência e insuficiência renal podem ser potencializadas durante o tratamento do câncer, principalmente pela associação com toxicidade medicamentosa e polifarmácia. Aspectos nutricionais e hemodinâmicos também podem aumentar a relação com a toxicidade. Por outro lado, o cuidado de suporte para pacientes idosos com câncer aumenta a expectativa de vida e melhora a morbidade. Portanto, a equipe multiprofissional deve acompanhar esses indivíduos com intervenções que busquem melhorar as chances de redução da morbi-mortalidade, restaurando a qualidade de vida após o diagnóstico.
27 October 2021 in Arquivos Catarinenses de Medicina
Objetivo: avaliar os aspectos clínico-epidemiológicos dos pacientes com carcinoma epidermóide de boca e orofaringe atendidos em um Hospital Universitário. Métodos: estudo descritivo dos casos de carcinoma de boca diagnosticados, no período de janeiro/2013 a dezembro/2018. Resultados: verificou-se maior acometimento de indivíduos do sexo masculino, brancos, na quinta década de vida, tabagistas e/ou etilistas; o sítio anatômico mais acometido foi o lábio; tumores labiais apresentaram tempo de evolução de 22,5 meses e foram diagnosticados em estádios iniciais; tumores de cavidade oral e orofaringe apresentaram tempo de evolução de 5 meses e foram diagnosticados em estádios tardios. Conclusão: Esforços devem ser realizados para o diagnóstico precoce do carcinoma de boca, principalmente entre pacientes tabagistas/etilistas, acima da quinta década de vida.