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Background: Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly originated from developed nations. There are still limited data on the molecular epidemiology of MBC in low- and middle-income countries. This study aims to evaluate the prevalence of mutations in the PI3K-AKT pathway and other actionable drivers in estrogen receptor (ER)+/HER2- MBC among Brazilian patients treated at a large institution representative of the nation's demographic diversity., Methods: We conducted a retrospective observational study using laboratory data (OC Precision Medicine). Our study included tumor samples from patients with ER+/HER2- MBC who underwent routine tumor testing from 2020 to 2023 and originated from several Brazilian centers within the Oncoclinicas network. Two distinct next-generation sequencing (NGS) assays were used: GS Focus (23 genes, covering PIK3CA , AKT1 , ESR1 , ERBB2 , BRCA1 , BRCA2 , PALB2 , TP53 , but not PTEN ) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI])., Results: Evaluation of tumor samples from 328 patients was undertaken, mostly (75.6%) with GS Focus. Of these, 69% were primary tumors, while 31% were metastatic lesions. The prevalence of mutations in the PI3K-AKT pathway was 39.3% (95% confidence interval, 33% to 43%), distributed as 37.5% in PIK3CA and 1.8% in AKT1 . Stratification by age revealed a higher incidence of mutations in this pathway among patients over 50 (44.5% vs 29.1%, p=0.01). Among the PIK3CA mutations, 78% were canonical (included in the alpelisib companion diagnostic non-NGS test), while the remaining 22% were characterized as non-canonical mutations (identifiable only by NGS test). ESR1 mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in BRCA1, BRCA2 , or PALB2 were identified in 3.9% of cases, while mutations in ERBB2 were found in 2.1%. No PTEN mutations were detected, nor were TMB high or MSI cases., Conclusion: We describe the genomic landscape of Brazilian patients with ER+/HER2- MBC, in which the somatic mutation profile is comparable to what is described in the literature globally. These data are important for developing precision medicine strategies in this scenario, as well as for health systems management and research initiatives., Competing Interests: Authors TR, AG, MP, LO, CR, LL, CB, MM, & RD were employed by the company Oncoclínicas & Co. TR – Research funding: AstraZeneca, Libbs. Speaker honoraria/advisory board: AstraZeneca, Daichi-Sankyo, Novartis, MSD, Lilly, Libbs. RD declares advisory role for Roche, Foundation Medicine, received a speaker’s fee from Roche, Ipsen, Amgen, Servier, Sanofi, Libbs, Merck Sharp & Dohme, Lilly, AstraZeneca, Janssen, Takeda, Bristol Myers Squibb, GlaxoSmithKline, Gilead, research grants from Merck, Novartis, Daiichi-Sankyo, GlaxoSmithKline and AstraZeneca, and is investor in Trialing Health, S.L. CB - Stock and Other Ownership Interests: Biomarker, MedSIR, Tummi. Speaker Honoraria: Novartis, Roche/Genentech, Pfizer, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, Eisai. Consulting or Advisory Role: Boehringer Ingelheim, Roche/Genentech, Novartis, GlaxoSmithKline, Eisai,Pfizer, AstraZeneca, Libbs, MSD Oncology, United Medical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Reinert, do Rego, Silva, Rodrigues, Koyama, Gonçalves, Pauletto, de Carvalho Oliveira, de Resende, Landeiro, Barrios, Mano and Dienstmann.)

Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising from the intestinal pacemaker cells of Cajal. They compose a heterogenous group of tumors due to a variety of molecular alterations. The most common gain-of-function mutations in GISTs are either in the KIT (60-70%) or platelet-derived growth factor receptor alpha ( PDGFRA ) genes (10-15%), which are mutually exclusive. However, a smaller subset, lacking KIT and PDGFRA mutations, is considered wild-type GISTs and presents distinct molecular findings with the activation of different proliferative pathways, structural chromosomal and epigenetic changes, such as inactivation of the NF1 gene, mutations in the succinate dehydrogenase ( SDH ), BRAF , and RAS genes, and also NTRK fusions. Currently, a molecular evaluation of GISTs is imperative in many scenarios, aiding in treatment decisions from the (neo)adjuvant to the metastatic setting. Here, we review the most recent data on the molecular profile of GISTs and highlight therapeutic implications according to distinct GIST molecular subtypes.

Osimertinib is a first-line treatment option for patients with metastatic non-small cell lung cancer (NSCLC) harbouring EGFR mutations. Pneumonitis is a severe adverse event (AE) related to osimertinib treatment which appears to be more frequent when associated with concurrent or previous anti-PD(L)1 exposure. Data regarding the efficacy and safety of osimertinib rechallenge, especially in the setting of central nervous system (CNS) metastases, are scarce. We herein describe a case of a 53-year-old patient with metastatic EGFR-mutated NSCLC, who developed pneumonitis after osimertinib treatment and was successfully rechallenged with 40 mg daily osimertinib, with CNS response. This dose reduction strategy may be an option for selected patients with brain metastases after tyrosine kinase inhibitors-induced AEs., Competing Interests: Dr de Castro Junior reports personal fees and other from AstraZeneca, personal fees and other from Roche, personal fees and other from Boehringer-Ingelheim, outside the submitted work. The other authors declare that they have no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

Purpose of Investigation: The aims of study were to evaluate potential prognostic laboratory factors in ovarian cancer (blood count parameters and tumor markers) and to relate these parameters with prognostic factors., Materials and Methods: The authors evaluated patients that underwent surgical treatment and with confirmed histopathologic diagnosis of ovarian cancer. Age, FIGO stage, type of surgery, serum levels of tumor markers, parameters of blood count, disease-free and overall survival were recorded. Mann-Whitney test was performed. The significance level was less than 0.05., Results: Higher levels of CA 125, CA 15.3, and platelets were found in the group with Stage hII/I, since hemoglobin levels were higher in stage I/II (p < 0.05). CEA levels were higher in the group of non-serous neoplasms (p < 0.05). Higher levels of CA125, CAIl5.3 and platelets were seen in the group histological grade 2/3 (p < 0.05)., Conclusion: CA 125, CA 15.3, hemoglobin, and platelets can be related prognostic factors in ovarian cancer.