Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report.

Autor:	Allegretti M; Translational Oncology Research, IRCSS Regina Elena National Cancer Institute, Rome, Italy., Barberi V; Medical Oncology 1, IRCSS Regina Elena National Cancer Institute, Rome, Italy., Ercolani C; Pathology, IRCSS Regina Elena National Cancer Institute, Rome, Italy., Vidiri A; Radiology and Diagnostic Imaging, IRCSS Regina Elena National Cancer Institute, Rome, Italy., Giordani E; Translational Oncology Research, IRCSS Regina Elena National Cancer Institute, Rome, Italy., Ciliberto G; Scientific Directorate, IRCSS Regina Elena National Cancer Institute, Rome, Italy., Giacomini P; Clinical Trial Center, IRCSS Regina Elena National Cancer Institute, Rome, Italy., Fabi A; Precision Medicine in Senology, Scientific Directorate - Department of Women and Child Health, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2023 Jan 11; Vol. 12, pp. 1050452. Date of Electronic Publication: 2023 Jan 11 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.1050452
Abstrakt:	Under therapeutic pressure aggressive tumors evolve rapidly. Herein, a luminal B/HER2-low breast cancer was tracked for >3 years during a total of 6 largely unsuccessful therapy lines, from adjuvant to advanced settings. Targeted next generation sequencing (NGS) of the primary lesion, two metastases and 14 blood drawings suggested a striking, unprecedented coexistence of three evolution modes: punctuated, branched and convergent. Punctuated evolution of the trunk was supported by en bloc inheritance of a large set (19 distinct genes) of copy number alterations. Branched evolution was supported by the distribution of site-specific SNVs. Convergent evolution was characterized by a unique asynchronous expansion of three actionable (OncoKB level 3A) mutations at two consecutive ESR1 codons. Low or undetectable in all the sampled tumor tissues, ESR1 mutations expanded rapidly in blood during HER2/hormone double-blockade, and predicted life-threatening local progression at lung and liver metastatic foci. Dramatic clinical response to Fulvestrant (assigned off-label exclusively based on liquid biopsy) was associated with clearance of all 3 subclones and was in stark contrast to the poor therapeutic efficacy reported in large liquid biopsy-informed interventional trials. Altogether, deconvolution of the tumor phylogenetic tree, as shown herein, may help to customize treatment in breast cancers that rapidly develop refractoriness to multiple drugs. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Allegretti, Barberi, Ercolani, Vidiri, Giordani, Ciliberto, Giacomini and Fabi.)
Databáze:	MEDLINE
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