Maria Augusta Soares

Prevalência da automedicação na população urbana portuguesa

To determine the prevalence of self-medication in a Portuguese urban population, a cross-sectional study was carried out in Lisbon (11 pharmacies) and Oporto (15 pharmacies). Data collection took place between November 1995 and September 1996, during 6 periods of 10 days each. The overall prevalence of self-medication found was 26,2%. Statistical significant differences were found between self-medication prevalence according to sex, age, educational level and professional status. Fifty percent of the individuals who have used drugs in self-medication did so with the pharmacist advice. The most frequent therapeutic groups used in self-medication were cough and cold preparations (23%) and analgesics (13,6%). Analysing each group separately, statistical significant differences for sex and age were found according to the variable self-medication.

Feline HER2 protein expression levels and gene status in feline mammary carcinoma: optimization of immunohistochemistry (IHC) and in situ hybridization (ISH) techniques.

Human epidermal growth factor receptor (HER2) is a tumor biomarker that when overexpressed and/or amplified is associated with a poor prognosis for women with breast cancer. This specific tumor subtype is eligible for a specific immunotherapy that increases survival period. However, in feline oncology, only a few studies have been performed on molecular characterization of feline (fHER2) in feline mammary carcinoma (FMC), and the available data are inconsistent. In this study, fHER2 protein levels and gene status in FMC were evaluated by immunohistochemistry and in situ hybridization. After being optimized, these techniques revealed that fHER2 is overexpressed in 33% of FMC cases, although fHER2 and fTOP2A gene amplification could not be observed. Our results support the possibility of using FMC as a natural model for comparative oncology. Additional data obtained may also improve the diagnostics, and consequently the treatment, of this type of tumor in veterinary medicine.

Ki-67 as a Prognostic Factor in Feline Mammary Carcinoma: What Is the Optimal Cutoff Value?

Ki-67 is a nuclear protein and a proliferation marker frequently used in establishing the prognosis for breast cancer patients. To investigate the prognostic value of the Ki-67 proliferation index in female cats with mammary carcinoma, a prospective study was conducted with 96 animals. The Ki-67 index of primary tumors (n = 96) was initially determined, and whenever possible, the Ki-67 index of regional lymph node metastasis (n = 38) and distant metastasis (n = 16) was also estimated. The optimal cutoff value for the Ki-67 index was determined by univariate and multivariate analysis. Ki-67 indices ≥14% were detected in 72.9% (70 of 96) of the tumors. Tumors with a Ki-67 index ≥14% were significantly associated with large size (P = .022), poor differentiation (P = .009), presence of necrotic areas (P = .008), estrogen receptor-negative status (P < .0001), fHER2-negative status (P = .003), and shorter overall survival (P = .012). Moreover, Ki-67 expression in the primary tumor was strongly and positively correlated with both regional metastasis (P < .0001; r = 0.83) and distant metastasis (P < .0001; r = 0.83), and was significantly higher in distant metastases when compared with the primary tumor (P = .0009). A similar correlation was also observed between regional and distant metastasis (P < .0001; r = 0.75). On the basis of the above results, the authors propose the adoption of the 14% value as the optimal cutoff for Ki-67 to identify tumors with high risk of disease progression.

Serum HER2 levels are increased in cats with mammary carcinomas and predict tissue HER2 status.

HER2 is overexpressed in about 30% of feline mammary carcinomas (FMC) and in 15-30% of breast cancers. Women with HER2-positive breast tumors are associated with shorter survival. This study aimed to optimize the detection and quantification of serum HER2 (sHER2) in cats and to evaluate its potential in diagnosing cats with mammary carcinomas (MC) overexpressing HER2. A prospective study was conducted in 60 queens showing MC and 20 healthy animals. Pre-operative serum samples were collected for sHER2 quantification using two immunoassays: ELISA and Dot blot assay. sHER2 levels were compared with tissue HER2 status assessed by immunohistochemistry. Queens with FMC showed significantly higher mean levels of sHER2 by both ELISA and Dot blot assay. A significant difference in the sHER2 levels was also found between cats with HER2-positive MC and those with low-expressing HER2 MC. A significant correlation between sHER2 levels and tumor HER2 status was also found, particularly when ELISA was used (r = 0.58, p < 0.0001). The value of 10 ng/ml was proposed as the optimal cutoff for both immunoassays by ROC analysis. Like in humans, sHER2 levels are increased in cats with MC HER2-positive, strongly suggesting that evaluation of sHER2 levels can be very useful in feline oncology. The results show that ELISA and Dot blot assay can replace the immunohistochemistry technique, due to their efficacy and lower costs for diagnostic purposes and for monitoring the response to anti-HER2 therapies in cats.

Immunophenotyping of primary and metastatic lesions in feline mammary tumors - are they equal?

*CIISA, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Portugal, Av. Universidade Técnica, 1300-477 Lisboa, Portugal. **CIISA, Departamento de Sanidade Animal, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Portugal, Av. Universidade Técnica, 1300-477 Lisboa, Portugal. ***Hospital Escolar, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Portugal, Av. Universidade Técnica, 1300-477 Lisboa, Portugal.

Serum SDF-1 levels are a reliable diagnostic marker of feline mammary carcinoma, discriminating HER2-overexpressing tumors from other subtypes

The feline mammary carcinoma (FMC) is the third most common tumor in cat, sharing many clinicopathological features with human breast cancer and thus, considered a suitable model for comparative oncology. Due to its poor prognosis, further studies are required to improve the diagnostic accuracy and treatment of cats with spontaneous mammary carcinoma. Recently, it was reported that the overexpression of stromal cell-derived factor-1 (SDF-1) has great value in human breast cancer diagnosis, suggesting that diagnostic tools and therapies targeting the SDF-1 ligand can improve the clinical outcome. In this study, we aimed to evaluate if serum SDF-1 levels can also be used as a biomarker of mammary carcinoma in cats and to analyze if serum SDF-1 levels are associated with clinicopathological features, linked to a specific FMC subtype or correlated with the tumor expression of SDF-1 receptor, the chemokine C-X-C motif receptor 4 (CXCR4). Results showed that cats with mammary carcinoma had significantly higher serum SDF-1 levels than healthy controls (p=0.035) and ROC analysis revealed that the best cut-off value to differentiate sick from healthy animals was 2 ng/ml (specificity: 80%; sensitivity: 57%; AUC=0.715). Significant associations were also found between cats with elevated serum SDF-1 concentrations (≥ 2 ng/ml) and HER2-overexpressing mammary carcinomas (Luminal B-like and HER2-positive subtypes, p<0.0001), CXCR4-negative mammary carcinomas (p=0.027), mammary carcinomas with small size (<3 cm, p=0.027) and tumors with low Ki-67 expression (p=0.012). No statistical associations were found between serum SDF-1 levels and overall or disease-free survival. In summary, our results show that serum SDF-1 levels can be used as a biomarker of feline mammary carcinoma, especially in cats with HER2-overexpressing mammary tumors. Data suggest that targeted therapies against the SDF-1 ligand and/or its CXC4 receptor may be effective for the treatment of FMC, as described for human breast cancer, strengthening the concept that spontaneous feline mammary carcinoma is a suitable model for comparative oncology.

Community pharmacists’ knowledge and perceptions on risk management plans in the Southern Region of Portugal

Abstract A Risk Management Plan (RMP) is a detailed description of the activities and interventions designed to identify, characterize, prevent, or minimize risks relating to medicine’s use. The objective of this article is to assess RMP-related knowledge of community pharmacists and explore the reasons behind any potential issues with its use. This study has two focus points: (1) A cross-sectional survey within a sample of pharmacies in the area covered by the South Pharmacovigilance Center; and (2) a focus group (FG) with key-informants, in order to increase the explanatory scope of quantitative results. In total, 41.6% of the participants in the study knew what a risk management plan was, but 50% rated their knowledge as poor. According to focus group participants, this lack of knowledge seems to be related to three main factors: (i) this subject not being addressed during graduation training; (ii) professionals’ attitude; and (iii) lack of communication among different stakeholders. It is recommended that there is enhanced academic training in risk management. There is an important call for attitudinal change interventions and further investigation in monitoring RMP use and impact. A closer articulation between the regulator, the pharmaceutical society, associations, and industry is needed to promote and boost this topic among community pharmacists.