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Review
. 2024 Sep:201:104427.
doi: 10.1016/j.critrevonc.2024.104427. Epub 2024 Jun 23.

Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer

Elena Guerini-Rocco  1 , Konstantinos Venetis  2 , Giulia Cursano  2 , Eltjona Mane  2 , Chiara Frascarelli  1 , Francesco Pepe  3 , Mariachiara Negrelli  4 , Edoardo Olmeda  4 , Davide Vacirca  2 , Alberto Ranghiero  2 , Dario Trapani  5 , Carmen Criscitiello  5 , Giuseppe Curigliano  5 , Christian Rolfo  6 , Umberto Malapelle  3 , Nicola Fusco  7
Affiliations
Review

Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer

Elena Guerini-Rocco et al. Crit Rev Oncol Hematol. 2024 Sep.

Abstract

Mutations in the estrogen receptor alpha gene (ESR1) can lead to resistance to endocrine therapy (ET) in hormone receptor-positive (HR+)/ HER2- metastatic breast cancer (MBC). ESR1 mutations can be detected in up to 40 % of patients pretreated with ET in circulating tumor DNA (ctDNA). Data from prospective randomized trials highlight those patients with HR+/HER2- MBC with detectable ESR1 mutations experience better outcomes when receiving novel selective estrogen receptor degraders (SERDs). There is a high need for optimizing ESR1 testing strategies on liquid biopsy samples in HR+/HER2- MBC, including a hugh quality workflow implementation and molecular pathology reporting standardization. Our manuscript aims to elucidate the clinical and biological rationale for ESR1 testing in MBC, while critically examining the currently available guidelines and recommendations for this specific type of molecular testing on ctDNA. The objective will extend to the critical aspects of harmonization and standardization, specifically focusing on the pathology laboratory workflow. Finally, we propose a clear and comprehensive model for reporting ESR1 testing results on ctDNA in HR+/HER2- MBC.

Keywords: CtDNA; Digital PCR; ESR1 testing; Metastatic breast cancer; Next-generation sequencing; Pathology report.

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Conflict of interest statement

Declaration of Competing Interest E.G-R. has relevant relationship (advisory fees, honoraria, travel accommodation and expenses, grants, and non-financial support) with AstraZeneca, Exact Sciences, GlaxoSmithKline (GSK), Novartis, Roche, Thermo Fisher Scientific unrelated to the current work. C.C. reported grants from Gilead, Seagen, personal fees from Pfizer, Lilly, Novartis, MSD, Daiichi Sankyo, and AstraZeneca outside the submitted work. G.C. reports funding from Astra Zeneca, Daichii Sankyo, Merck; consulting fees from BMS, Roche, Pfizer, Novartis, Lilly, Astra Zeneca, Daichii Sankyo, Merck, Seagen, Ellipsis; honoraria from Pfizer, Lilly; support for attending meetings from Roche, Pfizer. C.R. has received speaker honoraria from AstraZeneca, Roche, and MSD; advisory board honoraria from Inivata, Archer, Boston Pharmaceuticals, MD Serono, and Novartis; and institutional research funding for his work as Coordinating Principal Investigator from Pfizer and EMD Serono. U.M. has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera. N.F. has received honoraria for consulting, advisory role, speaker bureau, travel, and/or research grants from Merck Sharp & Dohme (MSD), Merck, Novartis, AstraZeneca, Roche, Menarini, Daiichi Sankyo, GlaxoSmithKline (GSK), Gilead, Adicet Bio, Sysmex, Reply, Veracyte Inc., Sakura, Leica Biosystems, Lilly. These companies had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and/or in the decision to publish the results. All other authors declare no potential conflicts of interest.