Saudade Andre - Academia.edu (original) (raw)

Papers by Saudade Andre

Frontiers in molecular biosciences, Apr 24, 2024

Virchows Archiv, Jun 6, 2014

Acta Médica Portuguesa, Feb 6, 2023

Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.com RESUMO Introdução: As anális... more Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.com RESUMO Introdução: As análises genómicas têm personalizado o tratamento adjuvante em cancro de mama localizado. O objetivo deste estudo foi avaliar o impacto de um protocolo institucional de análise genómica para de-escalação de quimioterapia. Métodos: Estudo de coorte prospetivo de todos os casos consecutivos de carcinoma da mama localizado com expressão positiva de receptores hormonais e sem sobre-expressão de human epidermal growth factor receptor 2, submetidos a um teste de quantificação de expressão de 21 genes para avaliação de score de recorrência (RS) entre agosto de 2015 e julho de 2018 num centro oncológico português. Para serem testadas, as doentes teriam de cumprir pelo menos um dos seguintes critérios de inclusão: i) luminal Alike , pT2pN0; ii) luminal Alike , 1-3 gânglios positivos e comorbilidades que constituam um maior risco para toxicidade induzida por quimioterapia; iii) pT1-2pN0, PR ≤ 20% ou Ki67 14%-40%. O tratamento adjuvante foi de-escalado para hormonoterapia isolada quando o RS foi inferior a 18. Foi medida a taxa de redução de prescrição de quimioterapia e o seu impacto clínico, a associação do RS com características patológicas e a exequilidade do protocolo. Resultados: Testámos 154 mulheres com mediana de idade de 61 anos (mínimo-máximo: 25-79), 69% pós-menopáusicas. Os tumores eram maioritariamente pT1 (55%), pN0 (82%), subtipo ductal invasivo (73%), G2 (86%), luminal B-like (69%) e estadio IA (85%). Obtivemos RS inferior a 18 em 60% das mulheres, com uma taxa de redução global de quimioterapia adjuvante de 65%. Esta análise genómica preveniu um evento adverso clinicamente relevante durante os primeiros seis meses de tratamento adjuvante por cada sete (intervalo de confiança 95%: 5-10) mulheres testadas. Considerando o cutoff mais recente para o RS, apenas 9% tiveram RS superior a 25, sendo que 11% das doentes com doença ganglionar teve RS superior a 25. Não houve correlação relevante entre RS e características anatomopatológicas. O protocolo não comprometeu o início atempado do tratamento adjuvante. Conclusão: Este protocolo evitou a exposição a quimioterapia em pelo menos seis em cada dez mulheres.

Breast Cancer Research and Treatment, May 3, 2021

Background Breast cancer (BC) is the most common cancer in women. In contrast, male BC is about 1... more Background Breast cancer (BC) is the most common cancer in women. In contrast, male BC is about 100 times less common than in women, being considered a rare disease. Male BC may be a distinctive subtype of BC and available data seems to indicate that male BC has a higher dependence on genetic variants than female BC. Nevertheless, the same prognostic and predictive markers are used to determine optimal management strategies for both male and female BC. Several studies have assessed the role of genetic polymorphisms (SNPs) in DNA repair genes in female BC susceptibility. However, data on male BC is scarce. Thus, the current study aimed to assess the role of SNPs in XRCC1, MUTYH and TP53 genes in a male cohort of BC, and, in addition, compare the male data with matched results previously genotyped in female BC patients. Methods The male BC cohort was genotyped through Real-Time PCR using TaqMan Assays for several SNPs previously analysed in Portuguese female BC patients. Results The results obtained indicate significant differences in BC susceptibility between males and females for the XRCC1 rs1799782, MUTYH rs3219489 and TP53 rs1042522 and rs8064946 variants. Conclusions In males, XRCC1 and TP53 variants, when in heterozygosity, seem to be related with lower susceptibility for BC, contrasting with higher susceptibility for a MUTYH variant in females. These findings may help to explain the difference in incidence of BC between the two sexes. Keywords Male Breast Cancer • Genetic variants in male and female breast cancer • DNA repair genes • TP53 • XRCC1 • MUTYH

Radiologia Brasileira, Apr 1, 2020

Objective: To review the imaging features of granular cell tumors of the breast (on mammography, ... more Objective: To review the imaging features of granular cell tumors of the breast (on mammography, ultrasound, and magnetic resonance imaging), establishing a pathological correlation, in order to familiarize radiologists with this entity and make them aware of the differential diagnoses, other than malignancy, of lesions with spiculated margins. Materials and Methods: We reviewed the medical records (from a clinical-pathology database and picture archiving and communication system) of five patients with a pathologically confirmed diagnosis of granular cell tumor of the breast, treated at the Portuguese Oncology Institute of Lisbon, in the city of Lisbon, Portugal, between January 2012 and December 2018. Results: All five tumors exhibited imaging features highly suggestive of malignancy (BI-RADS 5 lesions), namely spiculated margins, significant depth, and posterior acoustic shadowing (on ultrasound). One tumor showed a kinetic curve indicative of washout on magnetic resonance imaging, two were adherent to the pectoralis muscle, and one was accompanied by skin retraction. Pathology provided the definitive diagnosis in all cases. Conclusion: Granular cell tumors of the breast pose a diagnostic challenge because they can present with clinical and imaging features mimicking malignancy, and the diagnosis is therefore provided by pathology. Radiologists should be familiarized with this entity, so they can be aware of the fact that breast lesions with spiculated margins can be indicative of diagnoses other than malignancy.

Journal of Clinical Oncology, Jun 1, 2022

Background: Leptomeningeal carcinomatosis (LMC) remains associated with a poor outcome and effect... more Background: Leptomeningeal carcinomatosis (LMC) remains associated with a poor outcome and effective treatment options are not currently available. Knowledge about risk factors, diagnosis and optimal treatment of LMC is still limited. Methods: We performed a retrospective analysis of all consecutive patients with a solid tumor and LMC confirmed by CSF (cerebrospinal fluid)-positive cytology, diagnosed at our institution between January 2013 and November 2020. Clinical, imaging and cytologic data were collected. We used multivariable Cox regression models adjusted for age and Eastern Cooperative Oncology Group (ECOG) performance status to test the prognostic impact of clinical and treatment-related variables. Results: A total of 73 patients with LMC were identified, 75% female. The most common cancers were breast (51%, n = 37), lung (22%, n = 16), and melanoma (11%, n = 8). Most patients presented with intracranial hypertension (58%, n = 42), followed by cerebellar symptoms (20%, n = 15), radiculopathy (19%, n = 14), cranial nerve palsies (16%, n = 12), seizures (12%, n = 9), and other (4%, n = 3). More than half of patients (56%) had evidence of leptomeningeal involvement only, while 25% of patients (n = 18) had known central nervous system (CNS) metastases and 19% (n = 14) were diagnosed simultaneously with CNS metastases. Median time from primary tumor diagnosis to LMC was 32 months. Median overall survival (mOS) was 1.57 months (95% CI 1.17-2.32 months), with 15% of patients alive at 6 months (95% CI 9-26%). Patients with gynecological (7%, n = 5) and lung cancer had the best mOS (67 and 64 days, respectively), and patients with melanoma had the worst mOS (18 days). mOS in patients with evidence of meningeal involvement by MRI was 41 days, compared to 71.5 days in patients with a negative MRI. Starting a new systemic treatment was associated with a better prognosis (survival hazard ratio (HR) 0.39, 95% CI 0.21-0.75, p = 0.004). Forty patients (55%) received specific treatment for LMC. Neither intrathecal treatment nor radiation were associated with an improved outcome (HR 1.03, 95% CI 0.51-2.10, p = 0.930 and HR 0.60, 95% CI 0.30-1.17, p = 0.130, respectively). Presenting with seizures was significantly associated with a worse prognosis (HR 3.23, 95% CI 1.35-7.76, p = 0.009). In CSF cytology, both pleocytosis (> 5 cells/mm 3) and hyperproteinorhachia were individually associated with a worse prognosis (pleocytosis: HR 1.94, 95% CI 1.16-3.26, p = 0.012; hyperproteinorhachia: HR 2.61, 95% CI 1.28-5.32, p = 0.008). Conclusions: In this large series of patients diagnosed with LMC based on positive CSF cytology, the outcome was poor. Absence of leptomeningeal involvement by MRI and switching to a new treatment regimen were associated with a better outcome, likely reflecting tumor burden and patient selection. LMC will likely become more common as systemic treatment options and imaging improve and effective treatment options are an urgent and yet unmet need. Research Sponsor: None.

European Radiology, Oct 1, 2010

We present the case of a 45-year-old man with a long-standing history of a slow-growing left subm... more We present the case of a 45-year-old man with a long-standing history of a slow-growing left submandibular mass. Imaging was diagnostic as it disclosed an absent orthotopic thyroid gland and heterogeneous masses, with both solid and cystic components, as well as calcifications in the left sublingual/submandibular space and in the left paramedian aspect of the tongue base, consistent with double thyroid ectopia, originating from central and lateral thyroid anlages, respectively. Pathology confirmed an ectopic thyroid goiter in the left submandibular space with an incidental papillary microcarcinoma. Scintigraphy also demonstrated ectopic thyroid tissue in the left tongue base.

Histopathology, Jul 1, 2008

Prolactin receptor expression in gynaecomastia and male breast carcinoma Aims: Despite the well-e... more Prolactin receptor expression in gynaecomastia and male breast carcinoma Aims: Despite the well-established function of prolactin (PRL) in normal breast development, its role in breast cancer pathogenesis is still controversial. PRL activity is dependent on the activation of a transmembrane protein, the PRL receptor (PRLR). The aim was to evaluate and compare PRLR expression in gynaecomastia and male breast carcinoma (MBC). Methods and results: PRLR expression was detected immunohistochemically in 30 cases of gynaecomastia and 30 cases of MBC. The whole series was also assessed for oestrogen receptors (ER), progesterone receptors (PR) and androgen receptors (AR). A cutoff of 10% was used as the criterion for positivity. Histological type and tumour differentiation were evaluated. Pathological stage was assessed [Tumour Node Metastasis (TNM)-International Union Against Cancer system]. Statistical analysis was performed with Fisher's exact test. PRLR positivity was seen in 20% of gynaecomastia cases and in 60% of MBC cases (P = 0.003). In gynaecomastia immunoreactivity was predominantly observed in luminal cell borders, whereas in MBC the reactivity was heterogeneous and mainly cytoplasmic. There was no statistically significant correlation between PRLR expression and ER, PR, AR, pTNM, or histological grade. Conclusions: PRLR is significantly more expressed in MBC than in gynaecomastia, and with different patterns of reactivity, suggesting a role for PRL in male breast carcinogenesis.

The Breast, Aug 1, 1997

The present study evaluates the prognostic value of p53 protein overexpression assessed on histol... more The present study evaluates the prognostic value of p53 protein overexpression assessed on histological sections of a retrospective series of 353 invasive breast carcinomas (294 invasive ductal carcinomas not otherwise specified, eight mutinous and 51 invasive lobular carcinomas), with a median follow-up of 10 years, using the polyclonal antibody CM1 and a cutoff score of > 10% of stained nuclei. ~53 overexpression was not associated with invasive lobular or mucinous carcinomas (1.9% and 0% positive cases, respectively). In invasive ductal carcinomas (20.4% positive cases), there was a significant association between p53 overexpression and overall survival (P = 0.002), disease free interval (P = 0.005) and histological grade (P < 0.0001). Moreover, a statistically significant negative correlation between p53 immunoexpression and survival was found in high-grade (P = 0.016), pTU2 (P = 0.001/0.018), and pN0 (P = 0.001) tumours, indicating its usefulness as a marker of prognosis in these subgroups of invasive ductal breast carcinoma.

Breast Cancer Research and Treatment, Apr 19, 2015

MYC amplification has been reported as a prominent feature of secondary angiosarcomas (SAS). The ... more MYC amplification has been reported as a prominent feature of secondary angiosarcomas (SAS). The differential diagnosis between atypical vascular lesion (AVL) and low-grade angiosarcoma (AS) can be occasionally very difficult or even impossible, and MYC amplification status has been pointed as an important diagnostic tool to distinguish cutaneous vascular lesions of the breast. We assessed MYC amplification and protein expression status by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, in 49 patients diagnosed with breast AS, and 30 patients diagnosed with post-radiation AVL of the breast. Clinical and pathological features, and follow-up data were collected, and survival analyses were performed. Among 37 patients with SAS, twenty patients had tumors with high-level MYC amplification and protein overexpression (54 %). None of primary angiosarcomas (PAS) or AVL cases showed MYC amplification or protein expression. Concordance between MYC amplification (FISH) and protein expression (IHC) was 100 % in AVL, PAS, and SAS. Survival analysis of the SAS patients demonstrates that those with MYC amplification had a significantly worse overall survival compared to cases without MYC amplification (P = 0.035). There was a non-significant trend toward a poor disease-free survival between cases with and without MYC amplification (P = 0.155). Our findings show that MYC amplification is a highly specific but poorly sensitive marker for SAS and, therefore, a negative result does not exclude the diagnosis of angiosarcoma. MYC amplification was associated with adverse prognosis, suggesting a prognostic role of MYC amplification status on SAS of the breast.

Frontiers in Molecular Biosciences, Feb 7, 2023

Background: Around 40% of ER+/HER2-breast carcinomas (BC) present mutations in the PIK3CA gene. A... more Background: Around 40% of ER+/HER2-breast carcinomas (BC) present mutations in the PIK3CA gene. Assessment of PIK3CA mutational status is required to identify patients eligible for treatment with PI3Kα inhibitors, with alpelisib currently the only approved tyrosine kinase inhibitor in this setting. U-PIK project aimed to conduct a ring trial to validate and implement the PIK3CA mutation testing in several Portuguese centers, decentralizing it and optimizing its quality at national level. Methods: Eight Tester centers selected two samples of patients with advanced ER+/ HER2-BC and generated eight replicates of each (n = 16). PIK3CA mutational status was assessed in two rounds. Six centers used the cobas ® PIK3CA mutation test, and two used PCR and Sanger sequencing. In parallel, two reference centers (IPATIMUP and the Portuguese Institute of Oncology [IPO]-Porto) performed PIK3CA mutation testing by NGS in the two rounds. The quality of molecular reports describing the results was also assessed. Testing results and molecular reports were received and analyzed by U-PIK coordinators: IPATIMUP, IPO-Porto, and IPO-Lisboa. Results: Overall, five centers achieved a concordance rate with NGS results (allele frequency [AF] ≥5%) of 100%, one of 94%, one of 93%, and one of 87.5%, considering the overall performance in the two testing rounds. NGS reassessment of discrepancies in the results of the methods used by the Tester centers and the reference centers identified one probable false positive and two mutations with low AF (1-3%, at the analytical sensitivity threshold), interpreted as subclonal variants with heterogeneous representation in the tissue sections processed by the respective

Cancer Research, 2022

Background: The location of the variant in the BRCA2 gene may have a role on the differential ris... more Background: The location of the variant in the BRCA2 gene may have a role on the differential risk of hereditary breast-ovarian cancer (HBOC) families. Three Breast Cancer Cluster Regions (BCCR) have been previously identified in BRCA2: BCCR1- c.1-c.596; BCCR1’- c.772-c.1806; BCCR2- c.7394-c.8904. BCCR1 includes the Portuguese founder pathogenic variant (c.156_157insAlu), which explains up to 1/3 of hereditary breast cancer. As previously described one of the associated phenotypes of c.156_157insAlu is male breast cancer (MBC). We analyzed all MBC BRCA2 families registered in our program searching for a possible association between variant location in the BRCA2 gene and MBC. Methodology: This is a Portuguese, single-center, cross-sectional study, including all families identified with a pathogenic variant in the BRCA2 gene between December 1999 and December 2019. BRCA2 families with MBC cases were selected for further analysis including gene mapping of identified variants. The study...

Scientific Reports, 2019

The biochemical demands associated with tumor proliferation prompt neoplastic cells to augment th... more The biochemical demands associated with tumor proliferation prompt neoplastic cells to augment the import of nutrients to sustain their survival and fuel cell growth, with a consequent metabolic remodeling. Fatty acids (FA) are crucial in this process, since they have a dual role as energetic coins and building blocks. Recently, our team has shown that FATP1 has a pivotal role in FA transfer between breast cancer cells (BCCs) and non-cancerous cells in the microenvironment. We aimed to investigate the role of FATP1 in BCCs and also to explore if FATP1 inhibition is a promising therapeutic strategy. In patients’ data, we showed a higher expression of FATP1/SLC27A1 in TNBC, which correlated with a significant decreased overall survival (OS). In vitro, we verified that FA and estradiol stimulated FATP1/SLC27A1 expression in BCCs. Additionally, experiments with estradiol and PHTPP (ER-β antagonist) showed that estrogen receptor-β (ER-β) regulates FATP1/SLC27A1 expression, the uptake of ...

Revista Portuguesa de Endocrinologia, Diabetes e Metabolismo, 2016

Introduç ão: A citologia aspirativa de agulha fina (CAAF) tem um papel essencial na avaliaç ão da... more Introduç ão: A citologia aspirativa de agulha fina (CAAF) tem um papel essencial na avaliaç ão da doenç a nodular da tiroide. Permite não só reduzir o número de cirurgias desnecessárias em nódulos benignos, como possibilita o planeamento de uma abordagem cirúrgica adequada em doentes com doenç a maligna. No nosso serviç o realizaram-se 2.124 CAAF no período de 10 anos, sendo que, atualmente, são todas ecoguiadas. Objetivo: Avaliar a acuidade diagnóstica da CAAF num serviç o hospitalar. Métodos: Avaliaram-se, retrospetivamente, 204 processos dos doentes submetidos a citologia e, posteriormente, a cirurgia tiroideia, num período de 10 anos (2001-2010). Com base na correlaç ão cito-histológica, foi realizada uma análise de sensibilidade, especificidade, valor preditivo positivo e negativo. Resultados com um nível de significância < 0,05 foram considerados estatisticamente significativos. Resultados: O resultado citológico de benignidade verificou-se em 78% dos casos. Dos 22% restantes, 8,8% eram carcinomas e 13,2% eram tumores foliculares. O diagnóstico histológico foi de benignidade em 86,3% dos casos e de malignidade em 13,7%, dos quais 11,7% carcinomas papilares. No estudo da correlaç ão cito-histológica, verificou-se 79,4% de verdadeiros negativos, 15,7% de verdadeiros positivos, 3,4% de falsos negativos e 1,5% de falsos positivos. Dos casos falsos-negativos, 86% estiveram associados a nódulos de grandes dimensões (> 45 mm). A CAAF realizada no nosso serviç o apresenta uma sensibilidade de 95,9% e uma especificidade de 91,4%. Na amostra estudada, não existiram casos não diagnósticos. Conclusão: A CAAF realizada no nosso serviç o tem uma elevada especificidade e sensibilidade, com resultados semelhantes aos publicados na literatura internacional de referência.

International Journal of Molecular Sciences, 2020

Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequen... more Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of ATM, BRCA1, PALB2, RAD51B, and XRCC3. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables. Results: Only RAD51B and XRCC3 disclosed significant differences between tumor and gynecomastia (p < 0.0001 and p = 0.020, respectively). Assembled in a panel, RAD51B and XRCC3 promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89....

$Research paper thumbnail of Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma$

Journal of Clinical Pathology, Jul 1, 2001

Aims-To investigate the prognostic value of recently proposed flow cytometric S-phase fraction (S... more Aims-To investigate the prognostic value of recently proposed flow cytometric S-phase fraction (SPF) variables (average SPF and SPF tertiles) compared with conventional SPF, and to compare the one with the best predictive value with the immunohistochemical Ki-67 index in breast carcinoma. Methods-A short term follow up study (median, 39.6 months) of a large series of patients (n = 306) was conducted. DNA ploidy was analysed on fresh/frozen tumour samples by flow cytometry, and the SPF was calculated from the DNA histogram using an algorithm. The Ki-67 index was assessed on paraYn wax embedded material by immunohistochemistry (cut oV point, 10%). The two methods were compared by means of statistics, and the prognostic significance of both in relation to disease free survival (DFS) and overall survival (OS) was determined. Results-SPF and Ki-67 analysis was performed on 234 (76.5%) and 295 (96.4%) tumours, respectively. The two assessments were simultaneously available in 230 cases. All SPF variables analysed in the whole series significantly correlated with disease evolution, with the conventional median SPF (cut oV point, 6.1%) showing the highest predictive value in relation to both DFS (p = 0.0001) and OS (p = 0.0003). SPF tertiles and median SPF evaluated according to DNA ploidy status had no prognostic significance. The Ki-67 index showed a trend in relation to DFS (p = 0.086) that did not reach significance, and no correlation with OS was found (p = 0.264). The comparative analysis of SPF and Ki-67 revealed some agreement between the two methods (agreement, 69.13%; statistic, 0.3844; p < 0.001), especially in the subgroup of diploid tumours. Conclusions-Flow cytometric SPF is a better prognosticator than the Ki-67 index, but only SPF variables applied in the whole series show potential clinical usefulness.

Pathology Research and Practice, Dec 1, 1990

We studied a series of 44 consecutive cases of male breast carcinoma over a 14 year period in ord... more We studied a series of 44 consecutive cases of male breast carcinoma over a 14 year period in order to evaluate the clinico-pathological characteristics and the impact of some morphologic factors on prognosis. The age of the patients ranged from 38 to 84 years (mean 62 +/- 10.8). All the patients presented a painless mass, associated with nipple retraction in 13 cases (29.4%), skin ulceration in 12 cases (27.2%) and nipple discharge in 6 (13.6%). Microscopically all the tumors were infiltrating ductal carcinomas, 42 being of the NOS type. A better survival was associated with low mitotic index, T 1 tumors and absence of peritumoral lymphatic permeation. However, only these two parameters had statistical significance and were found to have predictive value on the prognosis of the disease. The degree of differentiation assessed according to Bloom and Richardson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s classification showed no influence on prognosis. Post surgical radiotherapy did not seem to influence the outcome of the disease.