Genetic Alterations Detected by Circulating Tumor DNA in HER2-Low Metastatic Breast Cancer

Whitney L. Hensing, Lorenzo Gerratana, Katherine Clifton, Arielle J. Medford, Marko Velimirovic, Ami N. Shah, Paolo D. Amico, Carolina Reduzzi, Qiang Zhang, Charles S. Dai, Elyssa N. Denault, Nusayba A. Bagegni, Mateusz Opyrchal, Foluso O. Ademuyiwa, Ron Bose, Amir Behdad, Cynthia X. Ma, Aditya Bardia, Massimo Cristofanilli, Andrew A. Davis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Purpose: About 50% of breast cancers are defined as HER2-low HER2-0 MBC. There were no differences in ERBB2 alterations and may benefit from HER2-directed antibody–drug conjugates. or oncogenic pathways between HER2-low and HER2-0 MBC. While tissue sequencing has evaluated potential differences in genomic Patients with HER2-positive MBC had more ERBB2 alterations profiles for patients with HER2-low breast cancer, genetic alterations in (RRR, 12.43; P ¼ 0.002 for amplification; RRR, 3.22; P ¼ 0.047 for circulating tumor DNA (ctDNA) have not been well described. mutations, in the hormone receptor–positive cohort), fewer ERS1 Experimental Design: We retrospectively analyzed 749 patients mutations (RRR, 0.458; P ¼ 0.029), and fewer ER pathway alterawith metastatic breast cancer (MBC) and ctDNA evaluation by tions (RRR, 0.321; P < 0.001). There was no difference in OS for Guardant360 from three academic medical centers. Tumors were HER2-low and HER2-0 MBC [HR, 1.01; 95% confidence interval classified as HER2-low, HER2-0 (IHC 0) or HER2-positive. Single-(CI), 0.79–1.29], while OS was improved in HER2-positive MBC nucleotide variants, copy-number variants, and oncogenic path-(HR, 0.32; 95% CI, 0.21–0.49; P < 0.001). ways were compared across the spectrum of HER2 expression. Conclusions: We observed a higher rate of PIK3CA mutations, Overall survival (OS) was evaluated by HER2 status and according but no significant difference in ERBB2 alterations, oncogenic path-to oncogenic pathways. ways, or prognosis, between patients with HER2-low and HER2-0 Results: Patients with HER2-low had higher rates of PIK3CA MBC. If validated, our findings support the conclusion that mutations [relative risk ratio (RRR), 1.57; P ¼ 0.024] compared with HER2-low MBC does not represent a unique biological subtype.

Original languageEnglish (US)
Pages (from-to)3092-3100
Number of pages9
JournalClinical Cancer Research
Issue number16
StatePublished - Aug 15 2023

ASJC Scopus subject areas

  • General Medicine


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