Rafael López López

investigators, and only WBRT and SRS intracranial radiotherapy were reported" has been removed.All changes appear in the HTML and PDF versions of the article.

Cancer therapy-related cardiac dysfunction (CTRCD), which commonly includes left ventricular dysfunction and heart failure, is the main adverse effect of anticancer therapy. In recent years several candidate genes studies and genome-wide association studies have identified common genetic variants associated with CTRCD, but evidence remains limited and few genetic variants are robust. A genome-wide meta-analysis of CTRCD was performed with 852 oncology patients receiving cancer therapy. DNA samples were genotyped and imputed to perform a GWAS meta-analysis for case–control (N = 852 (380 cases and 472 controls) and extreme phenotypes (N = 618 (78 cases and 472 controls) looking for genetic variants that predispose to CTRCD. The results were validated in a replicate cohort of 1,191 oncology patients (245 cases and 946 controls). Functional mapping of the replicated loci was then performed. The meta-analysis showed 9 and 17 loci suggestively associated (P-value < 1 × 10–5) with CTRCD in case–control and extreme phenotypes analyses, respectively. The 3q28 locus (rs rs7652759, P = 5.64 × 10–6) in the case–control analysis was the strongest signal, with up to 64 SNPs above the suggestive significance threshold. The rs7652759, an intergenic variant between TPRG1 and TP63 genes, was the only variant validated in the replication cohort (P-value = 0.01). Functional mapping of this significant locus revealed up to 5 new genes potentially involved in the CTRCD. We identified the intergenic region near TP63 as a novel CTRCD susceptibility locus. In the future, the genotyping of these markers could be considered in new CTRCD risk scores to improve preventive strategies in cardio-oncology.

Here we estimate the cost-effectiveness of olaparib in the Spanish National Health Service (SNHS) as adjuvant treatment of early germline mutations in the BRCA1/2 genes (gBRCAm) HER2-negative (HER2neg) breast cancer (BC) with high risk of recurrence. A semi-Markov model was adapted to the Spanish healthcare setting, using the perspective of the SNHS, and a lifetime horizon. Two scenarios were compared: receiving olaparib versus standard of care (SoC) treatment. The model comprised five health states and included the clinical results of the OlympiA trial, along with the direct healthcare costs associated with the use of early BC and subsequent treatment resources (€2023). A discount rate of 3% was applied for future cost and quality-of-life outcomes. A probabilistic sensitivity analysis (PSA) was carried out. The introduction of olaparib as adjuvant treatment for patients with early gBRCAm HER2neg BC with high risk of recurrence could involve an incremental cost of €44,273 and €50,164, with an improvement of 1.14 and 1.28 quality-adjusted life years (QALYs) for hormone receptor-positive (HR+) and triple-negative (TN) patients, respectively. Therefore, adjuvant olaparib could be cost-effective for early gBRCAm HER2neg BC, with an incremental cost-effectiveness ratio of €38,839/QALY and €39,084/QALY for HR+ and TN patients, respectively. The results from the PSA showed that 75.7% and 82.2% of the simulations fell below the €60,000/QALY threshold. Olaparib as adjuvant treatment could be cost-effective in gBRCAm patients with early HER2neg BC in Spain.

Long-term breast cancer survivors (LTBCS) are cases in which more than five years have elapsed since diagnosis and there is no evidence of disease. In Spain, the follow-up of these women currently takes the form of medical visits attended at Oncology Departments, though scientific societies recommend that this follow-up be conducted by Primary Care. The aims of this study were to quantify: (a) the prevalence of LTBCS patients in Galicia (Spain); and (b) medical visits attended by LTBCS at Oncology Departments, i.e., visits that could be undertaken in Primary Care. Retrospective case series including all LTBCS in Galicia diagnosed from January 1, 2001 through December 31, 2017, and alive at June 30, 2022. We sourced the data from Galician Health Service Information Systems, and performed a descriptive analysis. A total of 15,121 LTBCS were identified. Mean and median age at diagnosis was 57 years. Of the women included, 14,063 did not present with a new breast tumor (93.0%), 991 (6.6%) presented with a new tumor, and 67 presented with two or more new tumors (0.4%). Prevalence of LTBCS was 1.0% overall, 1.2% among women aged 30 years and over without new tumors, and 1.4% among women aged 50 years and over. LTBCS generated a total of 78,717 medical visits at Oncology Departments; 94.1% had attended 20 or fewer medical visits five years or more after diagnosis. Prevalence of LTBCS in Galicia is high, as is the number of medical visits attended at Oncology Departments. These findings would justify specific follow-up protocols being drawn up and implemented by Primary Care.

Abstract Approximatly 70% of breast cancer (BC) patients are Hormone Receptors (HR) positive, the most common subtype with the best prognosis. The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with Endocrine Therapy (ET) is tje standard firs-line therapy for HR+/HER2- metastatic BC. However, 20% of patients are intrinsically resistant, and those who initially respond often develop acquired resistance, making the management of resistant HR+/HER2- metastatic BC a significant clinical challenge. Clinical guidelines emphasize the need of comprehensive real-time monitoring of the dynamic mutational landscape during and after treatment to improve resistance prediction. Early detection of mutations in ESR1 and the PIK3 pathway usinf circulating tumor DNA (ctDNA) may allow the ending of ineffective endocrine therapies and initiation of alternative treatments for these patients, without performing tissue biopsies before radiological progression occurs. To achieve this, it is crucial to implement non-onvasive genotyping that allows better-adapted pharmacologiical interventions. However, clinical trials have been predominantly carried out with selected populations and single drugs (Palbociclib, Ribociclib or Abemaciclib). There is a lack of studies of optimal agreemnt between diagnostic methods, especially in liquid biopsy. There is no relieble data abaout PIK3CA or ESR1 status in ctDNA from real-world cohorts that could help to define the best testing strategy for the clinica routine. Therefore, it is imperative to establish evidence that the use of ddPCR is equally or more sensitive for ctDNA analysis than qPCR or NGS, the current gold standard methods. Aim: This study aims to perform a concordance analysis between NGS and ddPCR technologies for detecting mutations in PIK3CA and ESR1 by testing the ctDNA from HR+/HER2- metastatic breast cancer patients. M&amp;M: CANIPE is a randomised, open-label study performed al 14 Spanish hospitals in 6 autonomous communities. Patients aged 18 years or older, with confirmed HR+/HER2- breast cancer, stage IV, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 to 2, who iniciate first-line tratment with CDK4/6i plus aromatase inhibitors. All procedures followed the Helsinki Declaration guidelines and were approved by the Ethics Commitee of Santiago-Lugo under approval reference number 2022/386. All patients provide written informed consent. A total of 60 women were recruited at baseline (before therapy initiation) while 21 patients at 10 months after treatment. 40 mL of blood was obteined from each patient at both time points. For ddPCR, cfDNA was isolated from 5 mL of plasma using the QIAamp Circulating Nucleic Acid Kit (Qiagen, Venlo, The Netherlands). Multiplex ddPCR was performed with de Bio-Rad QX-200 system to identify PIK3CA mutations, including the most frequent variants (E542K, E545K, H1047L, H1047R, R88Q, N345K, C420R, E545A, E545G,Q546K), and ESR1 mutations (L536R, D538G, E380Q, Y537C, /537S, Y537N,S463P). A mutation was considered present if at least 6 mutated events were detected by ddPCR. Additionally, for NGS, cfDNA was isolated from 4 mL of plasma and analysed with the AVENIO ctDNA Expanded kit (Roche Diagnostics), which includes 77 genes, including PIK3CA and ESR1. An allele fraction od 0.5 % or higher was consideredindicative of a mutation. Results: At baseline, and considering the pre-defined criteria, ctDNA analysis detected PIK3CA mutations in 32.25% and 44.44% of patients by AVENIO and ddPCR, respectively. ESR1 mutations were detected in 3.22% and 9.37% by AVENIO and ddPCR, respectively. For PIK3CA mutations, the Kappa value was 0.62 (p-value: 0.0004) and 0.47 for ESR1 mutations (p-value: 0.0039). However, when NGS data was included for mutations with allele fraction less than 0.5%, the Kappa value was 0.92 for PIK3CA and 1 for ESR1, indicating almost perfect agreement bvetween the two technologies (p-value &amp;lt; 0.0001). Conclusion: The analysis of ctDNA bu Multiplex ddPCR of HR+/HER2- metastatic breas cancer patients represent a sensitive tool to identify PIK3CA and ESR1 mutations with a high concordance compared with the NGS, which is currently the reference technology. Citation Format: Teresa Curiel, Carmela Rodriguez, Aitor Rodriguez Casanova, Nerea González, Ramón Lago-Lestón, Martín Giráldez, Alicia Abalo, Carmen Abuín, Maribel Aibar, Patricia Palacios, Juan Cueva, Marta carmona, Alexia Cortegoso, Serafín Morales, Josep Gumá, Mariana López Flores, Yolanda Fernández, Isaura Fernádez, Ignacio Fernández, María Gión, Carolina Pena, Jesús García Mata, Andrea Saenz de Miera, Angel Díaz Lagares, Laura Muinelo Romay, Clotilde Costa, Rafael López López. Concordance Analysis of Non-Invasive determination techniques of PIK3CA and ESR1 mutations in patients with advanced luminal breast cancer. Study CANIPE [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-02-17.