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Breast cancer (BC) is the most prevalent malignancy affecting women worldwide, including Portugal. While the majority of BC cases are sporadic, hereditary forms account for 5-10% of cases. The most common inherited mutations associated with BC are germline mutations in the BReast CAncer (BRCA) 1/2 gene (gBRCA1/2). They are found in approximately 5-6% of BC patients and are inherited in an autosomal dominant manner, primarily affecting younger women. Pathogenic variants within BRCA1/2 genes elevate the risk of both breast and ovarian cancers and give rise to distinct clinical phenotypes. BRCA proteins play a key role in maintaining genome integrity by facilitating the repair of double-strand breaks through the homologous recombination (HR) pathway. Therefore, any mutation that impairs the function of BRCA proteins can result in the accumulation of DNA damage, genomic instability, and potentially contribute to cancer development and progression. Testing for gBRCA1/2 status is relevant for treatment planning, as it can provide insights into the likely response to therapy involving platinum-based chemotherapy and poly[adenosine diphosphate (ADP)-ribose] polymerase inhibitors (PARPi). The aim of this review was to investigate the impact of HR deficiency in BC, focusing on BRCA mutations and their impact on the modulation of responses to platinum and PARPi therapy, and to share the experience of Unidade Local de Saúde Santa Maria in the management of metastatic BC patients with DNA damage targeted therapy, including those with the Portuguese c.156_157insAlu BRCA2 founder mutation.

Mucosal melanoma accounts for 1% of all melanomas. It is more aggressive than cutaneous melanoma, and local excision provides the best disease-free survival. The vast majority of patients eventually develop metastases, with a metastatic pattern independent of the primary tumor site. While studies show that BRAF and KIT inhibitors have a role in the management of these patients, the actual treatment focus is on immunotherapy. Herein is described the case of a 79-year-old woman with metastatic mucosal melanoma and bone marrow infiltration causing disseminated intravascular coagulation, who was treated with an immunotherapy combination (anti-CTLA-4 and anti-PD-1 antibodies), achieving complete disease remission. This is the third case of melanoma with disseminated intravascular coagulation at presentation and the second case treated with immunotherapy in the literature, but the only one achieving disease remission.

Head and neck squamous cell carcinoma (HNSCC), the most prevalent pathological subtype of head and neck carcinoma (HNC), can be potentially cured if diagnosed at early stages and adequately treated. Still, most patients are diagnosed at stages III or IV disease, with estimated local and distant failure rates of 60% and 30%, respectively, notwithstanding aggressive multimodality curative intent treatment strategies approved. The excellent results of the EXTREME trial published in 2008 showing a median overall survival (mOS), of 10.1 months for patients with recurrent and/or metastatic (R/M) HNSCC, treated with platinum plus fluorouracil (5FU) and cetuximab, changed the standard of care (SOC), for these patients. The EXTREME regime was the first to evidence an overall survival (OS) benefit before the immunotherapy era, in this context. Two immunotherapy drugs are currently approved for treatment of R/M HNSCC in first or subsequent lines of treatment both for platinum-resistant and platinum sensitive disease: the anti-PD-1 agents nivolumab and pembrolizumab. But does this mean that there is no longer a place for the EXTREME regimen or for chemotherapy in general in R/M HNSCC treatment? And if there is, how to choose between available therapeutic options? In this article, the authors will address these questions by analyzing data from the main trials that investigated nivolumab and pembrolizumab in this setting.