Molecular characterization of triple negative breast cancer formaldehyde-fixed paraffin-embedded samples by data-independent acquisition proteomics.

Triple negative breast cancer accounts for 15%-20% of all breast carcinomas and is clinically characterized by an aggressive phenotype and poor prognosis. Triple negative tumors do not benefit from targeted therapies, so further characterization is needed to define subgroups with potential therapeutic value. In this work, the proteomes of 125 formalin-fixed paraffin-embedded samples from patients diagnosed with non-metastatic triple negative breast cancer were analyzed using data-independent acquisition + in a LTQ-Orbitrap Fusion Lumos mass spectrometer coupled to an EASY-nLC 1000. 1206 proteins were identified in at least 66% of the samples. Hierarchical clustering, probabilistic graphical models and Significance Analysis of Microarrays were combined to characterize proteomics-based molecular groups. Two molecular groups were defined with differences in biological processes such as glycolysis, translation and immune response. These two molecular groups showed also several differentially expressed proteins. This clinically homogenous dataset may serve to design new therapeutic strategies in the future.

Thrombosis in breast cancer patients on cyclin-dependent kinase inhibitors: Survival impact and predictive factors - A study by the cancer and thrombosis group of the spanish society of medical oncology (SEOM).

Thrombosis may be included in the profile of side effects associated with CDK4/6 inhibitors. Its significance might be greater than reported in randomized clinical trials. To investigate this, a retrospective, multicenter study was conducted. The primary objective was to calculate the incidence of thrombosis associated with CDK4/6 inhibitors. Secondary objectives included examining the impact of thrombosis on survival and identifying predictor variables for the development of venous thromboembolism (VTE) or arterial thrombosis (AT). A total of 986 patients were recruited. The incidence of VTE/AT associated with CDK4/6 inhibitor treatment during the follow-up period was 5.48 %. Survival analysis did not indicate that the development of VTE/AT during CDK4/6 inhibitor treatment significantly impacted patient survival (p = 0.133). In our analysis, two variables were found to be statistically significant (p < 0.05) as predictors of VTE/AT in breast cancer patients receiving CDK4/6 inhibitor therapy. These variables were the presence of central nervous system (CNS) metastasis with an odds ratio (OR) of 3.68 (95 % CI 1.18 - 11.49) and the use of abemaciclib with an OR of 2.3 (95 % CI 1.16 - 4.57).

Immune checkpoint inhibitors-associated thrombosis in patients with head and neck cancer: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS: /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identification of variables predictive of VTE/AT. RESULTS: A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no significant differences (p = 0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0-22.9) and the group that did not (median 9.86 months, 95% CI 6.3-13.4). The presence of liver metastases was predictive of VTE/AT (p < 0.05). CONCLUSIONS: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not significantly impact survival. The presence of liver metastases can predict these events.

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group.

PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification. RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375). CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

Incidence, risk factors, and evolution of venous thromboembolic events in patients diagnosed with pancreatic carcinoma and treated with chemotherapy on an outpatient basis.

BACKGROUND: Pancreatic carcinoma is one of the tumors associated with a higher risk for thromboembolic events, with incidence rates ranging from 5% to 41% in previous retrospective series. PATIENTS AND METHODS: We conducted a retrospective study in eleven Spanish hospitals that included 666 patients diagnosed with pancreatic carcinoma (any stage) between 2008 and 2011 and treated with chemotherapy. The main objective was to evaluate the incidence of venous thromboembolic events (VTE) in this population, as well as potential risk factors for thrombosis. The impact of VTE on mortality was also assessed. RESULTS: With a median follow-up of 9.3 months, the incidence of VTE was 22.1%; 52% were diagnosed incidentally. Our study was unable to confirm the ability of the Khorana score to discriminate between patients in the intermediate or high risk category for thrombosis. The presence of VTE proved to be an independent prognostic factor associated with increased risk of death (HR 2.39, 95% CI 1.96-2.92). Symptomatic events correlated with higher mortality than asymptomatic events (HR 1.72; 95% CI, 1.21-2.45; p = 0.002), but incidental VTE, including visceral vein thrombosis (VVT), negatively affected survival compared to patients without VTE. Subjects who developed VTE within the first 3 months of diagnosis of pancreatic carcinoma had lower survival rates than those with VTE after 3 months (HR 1.92, 95% CI 1.30-2.84; p<0.001). CONCLUSIONS: Pancreatic carcinoma is associated with a high incidence of VTE, which, when present, correlates with worse survival, even when thrombosis is incidental. Early onset VTE has a particularly negative impact.