Comprehensive genomic profiling of cell-free circulating tumor DNA detects response to Ribociclib plus Letrozole in a patient with metastatic breast cancer

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2022-12, Vol.12 (12), p.1818
• Main Authors: Silveira, Catarina, Sousa, Ana Carla, Martins Corredeira, Patrícia Isabel, Martins, Marta, Sousa, Ana Rita, Da Cruz Paula, Arnaud, Selenica, Pier, Brown, David N., Golkaram, Mahdi, Kaplan, Shannon, Zhang, Shile, Liu, Li, Weigelt, Britta, Reis-Filho, Jorge S., Costa, Luis, Carmo-Fonseca, Maria
• Format: Article
• Language: English
• Subjects: Aromatase Inhibitors; Biomarkers, Tumor - genetics; Biopsy; Blood; Bone cancer; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Case Report; CCND1 gene; circulating cell-free DNA; Circulating Tumor DNA - genetics; Deoxyribonucleic acid; DNA; DNA sequencing; Epidermal growth factor; Female; Genetic aspects; Genomes; Genomics; Humans; Letrozole - therapeutic use; Liquid biopsy; Mammography; Mastectomy; Medical prognosis; Metastases; Metastasis; Metastatic breast cancer; Methods; Missense mutation; Mutation; Nucleotide sequencing; Patients; Plasma; Ribociclib plus letrozole; Targeted cancer therapy; Tumors
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom12121818

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Analysis of cell-free circulating tumor DNA obtained by liquid biopsy is a non-invasive approach that may provide clinically actionable information when conventional tissue biopsy is inaccessible or infeasible. Here, we followed a patient with hormone receptor-positive and human epidermal growth factor receptor (HER) 2-negative breast cancer who developed bone metastases seven years after mastectomy. We analyzed circulating cell-free DNA (cfDNA) extracted from plasma using high-depth massively parallel sequencing targeting 468 cancer-associated genes, and we identified a clonal hotspot missense mutation in the PIK3CA gene (3:178952085, A > G, H1047R) and amplification of the CCND1 gene. Whole-exome sequencing revealed that both alterations were present in the primary tumor. After treatment with ribociclib plus letrozole, the genetic abnormalities were no longer detected in cfDNA. These results underscore the clinical utility of combining liquid biopsy and comprehensive genomic profiling to monitor treatment response in patients with metastasized breast cancer. This work was supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior, Portugal, through Fundos do Orçamento de Estado to Instituto de Medicina Molecular João Lobo Antunes (LA/P/0082/2020), and FCT/FEDER/POR Lisboa 2020, Programa Operacional Regional de Lisboa, PORTUGAL 2020 (LISBOA-01-0145-FEDER-016394), and FEDER/POR Lisboa 2020-Programa Operacional Regional de Lisboa, PORTUGAL 2020 (Infogene, 045300). C.S. was a recipient of a FCT fellowship (SFRH/BDE/110544/2015). This work was funded in part by the National Institutes of Health (NIH)/National Cancer Institute (NCI) Cancer Center Support Grant (P30 CA008748; MSK). J.S.R-F. and B.W. are funded in part by the NIH/NCI P50 CA247749 01 grant and a Breast Cancer Research Foundation grant. J.S.R.-F. is also funded in part by a Susan G Komen leadership grant, and B.W. by a Cycle for Survival grant.