Dynamic clonal remodelling in breast cancer metastases is associated with subtype conversion

Background: Changes in the clinical subtype (CS) and intrinsic subtype (IS) between breast cancer (BC) metastases and corresponding primary tumours have been reported. However, their relationship with tumour genomic changes remains poorly characterised. Here, we analysed the association between genomic remodelling and subtype conversion in paired primary and metastatic BC samples. Methods: A total of 57 paired primary and metastatic tumours from GEICAM/2009-03 (ConvertHER, NCT01377363) study participants with centrally assessed CS (n = 57) and IS (n = 46) were analysed. Targeted capture and next-generation sequencing of 202 genes on formalin-fixed paraffin-embedded samples was performed. Th…

Primary results of the first nationwide molecular screening program in Spain for patients with advanced breast cancer (AGATA SOLTI-1301 study)

Abstract OT-13-06: Solti-1503 PROMETEO: Talimogene laherparepvec (T-VEC) + atezolizumab combination in early breast cancer

Abstract Background Residual disease (RD) after standard neoadjuvant chemotherapy (NAC) is composed of drug resistant cells and associates with increased risk of relapse, especially in triple negative, HER2-positive, and highly proliferative Luminal tumors. Immunotherapy combinations can induce of specific anti-tumor immune responses, such as those mediated by T-cells, and which might represent an additional strategy for the control or elimination of residual tumor cells. Preliminary results in melanoma showed that the combination of T-VEC with an anti PD-L1 or anti CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each agent.…

Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer.

Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We ident…

The GATA3 X308_Splice breast cancer mutation is a hormone context-dependent oncogenic driver

AbstractAs the catalogue of oncogenic driver mutations is expanding, it is becoming clear that alterations in a given gene should not be lumped into one single class, since they might have different functions. The transcription factorGATA3is a paradigm of this. Here, we address the functions of the most commonGATA3mutation (X308_Splice) which generates a neoprotein that we designate as neoGATA3, associated with good patient prognosis. Based on extensive analyses of molecular and clinical data from approximately 3000 breast cancer patients, supported by mechanistic studiesin vitro, we show that neoGATA3 interferes with the transcriptional programs controlled by estrogen and progesterone rece…

SOLTI-1503 PROMETEO TRIAL: combination of talimogene laherparepvec with atezolizumab in early breast cancer

New treatment strategies such as immune checkpoint inhibitors and oncolytic viruses are opening new possibilities in cancer therapy. Preliminary results in melanoma and other tumors showed that the combination of talimogene laherparepvec with an anti-PD-1/PD-L1 or anti-CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each agent. The presence of residual cancer after neoadjuvant chemotherapy in early breast cancer patients is an unmet medical need. SOLTI-1503 PROMETEO is a window of opportunity trial, which evaluates the combination of talimogene laherparepvec in combination with atezolizumab in women with operable HER2-negati…

First Nationwide Molecular Screening Program in Spain for Patients With Advanced Breast Cancer: Results From the AGATA SOLTI-1301 Study

Anàlisi de seqüències d'ADN; Subtipus PAM50; Genètica molecular Análisis de secuencias de ADN; Subtipo PAM50; Genética molecular DNA sequence analyses; PAM50 subtype; Molecular genetic Background: The SOLTI-1301 AGATA study aimed to assess the feasibility of a multi-institutional molecular screening program to better characterize the genomic landscape of advanced breast cancer (ABC) and to facilitate patient access to matched-targeted therapies in Spain. Methods: DNA sequencing of 74 cancer-related genes was performed using FFPE tumor samples in three different laboratories with three different gene panels. A multidisciplinary advisory board prospectively recommended potential targeted trea…

A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer

No luminal; Subtipus intrínsec; Càncer de mama No luminal; Subtipo intrínseco; Cáncer de mama Non-luminal; Intrinsic subtype, Breast cancer Background: In hormone receptor-positive (HR+)/HER2-negative breast cancer, the HER2-enriched and Basal-like intrinsic subtypes are associated with poor outcome, low response to anti-estrogen therapy and high response to chemotherapy. To date, no validated biomarker exists to identify both molecular entities other than gene expression. Methods: PAM50 subtyping and immunohistochemical data were obtained from 8 independent studies of 1,416 HR+/HER2-negative early breast tumors. A non-luminal disease score (NOLUS) from 0 to 100, based on percentage of estr…