Showing papers by "Carlos Martínez-Pérez published in 2023"
TL;DR: In this paper , the authors conducted a thorough review of the published literature to summarize the evidence to date, including studies of how NET compares to neoadjuvant chemotherapy, which NET agents are preferable, and the optimal duration of NET.
Abstract: ABSTRACT Introduction While endocrine therapy is the standard-of-care adjuvant treatment for hormone receptor-positive (HR+) breast cancers, there is also extensive evidence for the role of pre-operative (or neoadjuvant) endocrine therapy (NET) in HR+ postmenopausal women. Areas covered We conducted a thorough review of the published literature, to summarize the evidence to date, including studies of how NET compares to neoadjuvant chemotherapy, which NET agents are preferable, and the optimal duration of NET. We describe the importance of on-treatment assessment of response, the different predictors available (including Ki67, PEPI score, and molecular signatures) and the research opportunities the pre-operative setting offers. We also summarize recent combination trials and discuss how the COVID-19 pandemic led to increases in NET use for safe management of cases with deferred surgery and adjuvant treatments. Expert opinion NET represents a safe and effective tool for the management of postmenopausal women with HR+/HER2- breast cancer, enabling disease downstaging and a wider range of surgical options. Aromatase inhibitors are the preferred NET, with evidence suggesting that longer regimens might yield optimal results. However, NET remains currently underutilised in many territories and institutions. Further validation of predictors for treatment response and benefit is needed to help standardise and fully exploit the potential of NET in the clinic.
1 citations
TL;DR: The International Symposium on Early and Lower Vertebrates (ISELV) aims to promote the study of the origin and early evolution of our own evolutionary lineage as mentioned in this paper , which has been organized 15 times prior to the latest conference in Valencia, which marked the 16th edition and the first time it was held in Spain in over 50 years.
Abstract: The International Symposium on Early and Lower Vertebrates (ISELV) aims to promote the study of the origin and early evolution of our own evolutionary lineage. This volume serves as an example of the most recent symposium held in Valencia, Spain, in June 2022. Since its inception in 1967, the ISELV has been organized 15 times prior to the latest conference in Valencia, which marked the 16th edition and the first time it was held in Spain in over 50 years. This symposium stands out as the sole recurring international meeting exclusively dedicated to the Palaeozoic vertebrate research community, putting special emphasis on topics concerning the origin, diversity, and early evolution of vertebrates (including the first tetrapods). The compilation presented in this volume represents the culmination of these conferences and serves as our tribute to two distinguished researchers in the field of Early Vertebrates: Dr. Philippe Janvier from the Muséum National d’Histoire Naturelle in Paris and Dr. Tiiu Märss from Tallinn University of Technology in Estonia.
TL;DR: In this paper , the first Devonian vertebrates remains from Peru were reported, represented by three jaw fragments assigned to Pucapampella and three fin plates of Zamponiopteron.
Abstract: Devonian vertebrates in South America are notably scarce compared with other continents, becoming this circumstance particularly evident in Peru, where no Palaeozoic vertebrates have been formally reported so far. In this paper, we report, figure and describe the first Devonian vertebrates remains from Peru recovered in the Puno region, south-eastern of the country. The remains belong to the very unusual group of Emsian to Eifelian stem-chondrichthyan Pucapampella and Zamponiopteron that characterise the vertebrate fauna of the so-called marine “Malvinokaffric Realm”. The remains studied are represented by three jaw fragments assigned to Pucapampella, and three fin plates of Zamponiopteron. These records increase the palaeogeographic distribution of this assemblage in the Palaeozoic of Gondwana, but more relevant, our findings highlight the potential of the Peruvian outcrops to contribute to the knowledge on the diversity and distribution of the early vertebrate faunas in the South American continent.
TL;DR: Martinez-Perez et al. as discussed by the authors performed a multi-omics analysis of primary ER+ BCs matched with recurrences on or after completion of adjuvant endocrine therapy (aET).
Abstract:
Background: 80% of all breast cancers (BCs) are ER-positive (ER+). Not all respond to adjuvant endocrine therapy (aET) and a significant number develop endocrine resistance and recur. The basis for primary and acquired endocrine resistance is poorly understood. A multiomics analysis of primary ER+ BCs matched with recurrences on or after completion of aET has been performed. Patients: A unique cohort of 520 women with matched primary and recurrent ER+, HER2-negative (HER2-) BC is being analysed. In the first subset of 75, all had surgery to clear margins, followed by aET. The endocrine therapy given was tamoxifen (66%), aromatase inhibitors (AI) (28%: 17% letrozole, 6% anastrozole, 2% exemestane, and 3% a succession of 2 different AIs), or a combination of tamoxifen and an AI (6%). aET duration was 5 years, unless the patient stopped treatment or developed a recurrence sooner. 16/75 patients (21%) had positive lymph nodes. All patients developed recurrences: local in 59/75, concurrent local and nodal in 13/75 and lymph node-only in 3/75. Median time to recurrence was 4.1 years (range: 0.7-29 years). 62% of patients were on aET at the time of recurrence. All patients have long-term follow-up. Methods: DNA and RNA were extracted from matched primary and recurrence BC tissue samples. Targeted DNA-exome and whole-genome expression analyses were performed. A custom targeted DNA panel was used to study genes implicated in endocrine therapy resistance (ETR): this included 73 different targets, selected based on our previous full-exome sequencing of sequential ET recurrences and those implicated in the literature and in curated somatic and cancer mutation databases. Somatic mutations and copy number alterations (CNA) were determined. Differential gene expression analysis was performed using two-class unpaired Significance Analysis of Microarrays (SAM). Validation of pathways implicated in ETR using NanoString GeoMx protein analysis is ongoing. Results: Targeted DNA-exome profiling identified 1 or 2 potential driver mutations in all but a few primary samples. Multiple aberrations and a highly diverse mutational landscape were observed in all the recurrences. Matched breast and lymph node samples from synchronous recurrences had very similar somatic profiles. Changes significantly enriched in recurrent samples included somatic aberrations in well-established drivers such as MAP3K1, PIK3CA, TP53 and CDH1, as well as ESR1. Aberrations were also common in PTEN and in ER-associated factors FOXA1 and GATA3. Transcriptomic analysis revealed a number of pathways implicated in resistance, including ER, HER2, GATA3, AKT, RAS and p63 signalling. A panel-based, targeted DNA sequencing approach for mutational profiling allowed capture of relevant mutational profiles linked to ETR in a cost-effective manner compared with traditional whole-exome sequencing. Ongoing analysis has linked mutational profiles to specific endocrine agents and has allowed us to demonstrate significant differences between recurrences on aET compared with those after completion of aET. Multiomics profiling of the remaining samples in the cohort is underway. Discussion: This multiomics study provides the largest cohort to-date of matched early and recurrent ER+/HER2- BCs. It has shed new light on how different adjuvant endocrine agents can affect primary drivers and lead to complex somatic and transcriptomic changes in recurrent disease. This work confirms that the mechanisms of endocrine resistance are diverse and has already identified mechanisms underlying ETR and clinically meaningful biomarkers of ETR, including potentially actionable mutations and targets.
Citation Format: Carlos Martinez-Perez, Charlene Kay, James Meehan, J Michael Dixon, Arran K Turnbull. PD10-09 Multiomics analysis of matched ER+ primary and recurrent breast cancers on or after adjuvant endocrine therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD10-09.