TY - JOUR
T1 - First Nationwide Molecular Screening Program in Spain for Patients With Advanced Breast Cancer
T2 - Results From the AGATA SOLTI-1301 Study
AU - Pernas, Sonia
AU - Villagrasa, Patricia
AU - Vivancos, Ana
AU - Scaltriti, Maurizio
AU - Rodón, Jordi
AU - Burgués, Octavio
AU - Nuciforo, Paolo
AU - Canes, Jordi
AU - Paré, Laia
AU - Dueñas, Marta
AU - Vidal, Maria
AU - Cejalvo, Juan Miguel
AU - Perelló, Antonia
AU - Llommbard-Cussac, Antonio
AU - Dorca, Joan
AU - Montaño, Alvaro
AU - Pascual, Tomás
AU - Oliveira, Mafalda
AU - Ribas, Gloria
AU - Rapado, Inmaculada
AU - Prat, Aleix
AU - Ciruelos, Eva
N1 - Publisher Copyright:
© Copyright © 2021 Pernas, Villagrasa, Vivancos, Scaltriti, Rodón, Burgués, Nuciforo, Canes, Paré, Dueñas, Vidal, Cejalvo, Perelló, Llommbard-Cussac, Dorca, Montaño, Pascual, Oliveira, Ribas, Rapado, Prat and Ciruelos.
PY - 2021/11/4
Y1 - 2021/11/4
N2 - 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 treatments. The primary objective was to determine the success of matching somatic DNA alteration to an experimental drug/drug class. Results: Between September 2014 and July 2017, 305 patients with ABC from 10 institutions were enrolled. Tumor sequencing was successful in 260 (85.3%) patients. Median age was 54 (29-80); most tumors were hormone receptor-positive/HER2-negative (74%), followed by triple-negative (14.5%) and HER2-positive (11.5%). Ninety-seven (37%) tumor samples analyzed proceeded from metastatic sites. Somatic mutations were identified in 163 (62.7%) patients, mostly in PIK3CA (34%), TP53 (22%), AKT1 (5%), ESR1 (3%), and ERBB2 (3%) genes. Significant enrichment of AKT1 mutation was observed in metastatic versus primary samples (9% vs. 2%; p=0.01). Genome-driven cancer therapy was recommended in 45% (n=116) of successfully screened patients, 11% (n=13) of whom finally received it. Among these patients, 46.2% had a PFS of ≥6 months on matched therapy. Conclusions: AGATA is the first nationwide molecular screening program carried out in Spain and we proved that implementing molecular data in the management of ABC is feasible. Although these results are promising, only 11% of the patients with genome-driven cancer therapy received it.
AB - 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 treatments. The primary objective was to determine the success of matching somatic DNA alteration to an experimental drug/drug class. Results: Between September 2014 and July 2017, 305 patients with ABC from 10 institutions were enrolled. Tumor sequencing was successful in 260 (85.3%) patients. Median age was 54 (29-80); most tumors were hormone receptor-positive/HER2-negative (74%), followed by triple-negative (14.5%) and HER2-positive (11.5%). Ninety-seven (37%) tumor samples analyzed proceeded from metastatic sites. Somatic mutations were identified in 163 (62.7%) patients, mostly in PIK3CA (34%), TP53 (22%), AKT1 (5%), ESR1 (3%), and ERBB2 (3%) genes. Significant enrichment of AKT1 mutation was observed in metastatic versus primary samples (9% vs. 2%; p=0.01). Genome-driven cancer therapy was recommended in 45% (n=116) of successfully screened patients, 11% (n=13) of whom finally received it. Among these patients, 46.2% had a PFS of ≥6 months on matched therapy. Conclusions: AGATA is the first nationwide molecular screening program carried out in Spain and we proved that implementing molecular data in the management of ABC is feasible. Although these results are promising, only 11% of the patients with genome-driven cancer therapy received it.
KW - DNA sequence analyses
KW - PAM50 subtype
KW - breast cancer
KW - molecular genetic
KW - molecular targeted therapy
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U2 - 10.3389/fonc.2021.744112
DO - 10.3389/fonc.2021.744112
M3 - Article
C2 - 34804931
AN - SCOPUS:85119446886
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 744112
ER -