Browsing by Author "Negreiros, I"
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- Case report: Primary CDK4/6 inhibitor and endocrine therapy in locally advanced breast cancer and its effect on gut and intratumoral microbiotaPublication . Vilhais, G; Alpuim Costa, D; Fontes-Sousa, M; Ribeiro, PC; Martinho, F; Botelho de Sousa, C; Santos, CR; Negreiros, I; Canastra, A; Borralho, P; Guia Pereira, A; Marçal, C; Germano Sousa, J; Chaleira, R; Rocha, JC; Calhau, C; Faria, ALocally advanced breast cancer poses significant challenges to the multidisciplinary team, in particular with hormone receptor (HR) positive, HER2- negative tumors that classically yield lower pathological complete responses with chemotherapy. The increasingly significant use of CDK 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) in different breast cancer settings has led to clinical trials focusing on this strategy as a primary treatment, with promising results. The impact of the microbiota on cancer, and vice-versa, is an emerging topic in oncology. The authors report a clinical case of a postmenopausal female patient with an invasive breast carcinoma of the right breast, Luminal B-like, staged as cT4cN3M0 (IIIB). Since the lesion was considered primarily inoperable, the patient started letrozole and ribociclib. Following 6 months of systemic therapy, the clinical response was significant, and surgery with curative intent was performed. The final staging was ypT3ypN2aM0, R1, and the patient started adjuvant letrozole and radiotherapy. This case provides important insights on primary CDK4/6i plus ET in locally advanced unresectable HR+/HER2- breast cancer and its potential implications in disease management further ahead. The patient’s gut microbiota was analyzed throughout the disease course and therapeutic approach, evidencing a shift in gut microbial dominance from Firmicutes to Bacteroidetes and a loss of microbial diversity following 6 months of systemic therapy. The analysis of the intratumoral microbiota from the surgical specimen revealed high microbial dissimilarity between the residual tumor and respective margins.
- Expression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast CancerPublication . Saraiva, DP; Azeredo-Lopes, S; Antunes, A; Salvador, R; Borralho, P; Assis, B; Pereira, IL; Seabra, Z; Negreiros, I; Jacinto, A; Braga, S; Cabral, MGNeoadjuvant chemotherapy (NACT) is common in breast cancer (BC) treatment, though more than half of the patients lack an effective response. Therefore, new predictive biomarkers and alternative therapies are crucial. Previously, we proposed HLA-DR-expressing cytotoxic T lymphocytes (CTLs) as a potential biomarker of the response to NACT. To validate this observation and further investigate these cells, 202 BC patients were enrolled. Flow cytometry analyses were performed in 61 biopsies and 41 blood samples pre-NACT and 100 non-NACT tumor samples. All the patients were followed up for 34 months. Blood-isolated immune cells were cultured with BC cell lines in a 3D system. We confirmed that HLA-DR level in CTLs is a highly sensitive, specific, and independent biomarker to predict response to NACT and developed a predictive probability model. This biomarker was also associated with progression-free survival, regardless of the treatment. The clinical observations are substantiated by the anti-tumor properties of HLA-DR-expressing CTLs. Intriguingly, HLA-DR level in CTLs can be modulated ex vivo, boosting their capacity to kill tumor cells synergistically with doxorubicin. Thus, HLA-DR expression in CTLs is a validated tool to select patients that will actually benefit from NACT, and its stimulation might be a novel therapeutic approach for BC.
- Human Microbiota and Breast Cancer—Is There Any Relevant Link?—A Literature Review and New Horizons Toward Personalised MedicinePublication . Alpuim Costa, D; Nobre, JG; Batista, MV; Ribeiro, C; Calle, C; Cortes, A; Marhold, M; Negreiros, I; Borralho, P; Brito, M; Cortes, J; Braga, SA; Costa, LBreast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Recently, gut microbiota dysbiosis emerged as a key player that may directly and/or indirectly influence development, treatment, and prognosis of BC through diverse biological processes: host cell proliferation and death, immune system function, chronic inflammation, oncogenic signalling, hormonal and detoxification pathways. Gut colonisation occurs during the prenatal period and is later diversified over distinct phases throughout life. In newly diagnosed postmenopausal BC patients, an altered faecal microbiota composition has been observed compared with healthy controls. Particularly, β-glucuronidase bacteria seem to modulate the enterohepatic circulation of oestrogens and their resorption, increasing the risk of hormone-dependent BC. Moreover, active phytoestrogens, short-chain fatty acids, lithocholic acid, and cadaverine have been identified as bacterial metabolites influencing the risk and prognosis of BC. As in gut, links are also being made with local microbiota of tumoural and healthy breast tissues. In breast microbiota, different microbial signatures have been reported, with distinct patterns per stage and biological subtype. Total bacterial DNA load was lower in tumour tissue and advanced-stage BC when compared with healthy tissue and early stage BC, respectively. Hypothetically, these findings reflect local dysbiosis, potentially creating an environment that favours breast tumour carcinogenesis (oncogenic trigger), or the natural selection of microorganisms adapted to a specific microenvironment. In this review, we discuss the origin, composition, and dynamic evolution of human microbiota, the links between gut/breast microbiota and BC, and explore the potential implications of metabolomics and pharmacomicrobiomics that might impact BC development and treatment choices toward a more personalised medicine. Finally, we put in perspective the potential limitations and biases regarding the current microbiota research and provide new horizons for stronger accurate translational and clinical studies that are needed to better elucidate the complex network of interactions between host, microorganisms, and drugs in the field of BC.
- Human Microbiota and Breast Cancer—Is There Any Relevant Link?—A Literature Review and New Horizons Toward Personalised MedicinePublication . Alpuim Costa, D; Nobre, JG; Batista, MV; Ribeiro, C; Calle, C; Cortes, A; Marhold, M; Negreiros, I; Borralho, P; Brito, M; Cortes, J; Braga, SA; Costa, L
- Lawsonella clevelandensis as the causative agent of a breast abscessPublication . Favila Menezes, M; Sousa, MJ; Paixão, P; Atouguia, J; Negreiros, I; Simões, MJLawsonella clevelandensis is a Gram-stain-positive, partially acid-fast, anaerobic, being considered a new species within a new genus in the suborder Corynebacterineae. There are only a few cases reported worldwide. This is a fastidious microorganism, difficult to identify by conventional methods, leading to inappropriate treatments. The authors report a case of a 29-year-old woman with a 3-week evolution of a breast nodule. There was a family history of breast carcinoma. Samples were collected for histological and microbiological examination. Gram staining revealed Gram-positive filamentous bacilli, acid-fast-positive. The cultural examination revealed a Lawsonella clevelandensis that was confirmed by molecular methods. At the last follow up, the evolution was favorable; the abscess was resolved, with no evidence of recurrence. To our knowledge the present case was the first reported in Europe.