ArticleJournal of experimental & clinical cancer research : CR2024
Monitoring changing patterns in HER2 addiction by liquid biopsy in advanced breast cancer patients.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05735392 (Liquid Biopsy), which is not on this map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Liquid Biopsy: Intercepting Mutational Trajectories of HER2 Breast Cancer Inpatients Under T-DM1 Treatment
Who cites it
7 citing papers in PubMed.
- Changes in plasma cfDNA ERBB2 copy number reflect prognosis in HER2-positive gastric cancer: a correlative analysis of the KSCC-TROX A2 study.International journal of clinical oncology · 2026Trial
- Soluble isoforms of EGFR family in breast cancer: Advances and clinical relevance (Review).Oncology letters · 2026Review
- Circulating tumor DNA and Response Evaluation Criteria In Solid Tumors: ctDNA-RECIST proof-of-concept in HER2-positive metastatic breast cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Receptor Discordance and Molecular Subtype Changes in Visceral Metastases of Breast Cancer.Breast cancer (Dove Medical Press) · 2026Article
- HER2-Low Breast Cancer at the Interface of Pathology and Technology: Toward Precision Management.Biomedicines · 2025Review
- Liquid biopsy in breast cancer: clinical implications of ctDNA and CTCs in diagnosis, treatment and monitoring.Molecular and cellular biochemistry · 2025Review
- Trastuzumab deruxtecan: expanding the role of HER2-targeted therapy in solid tumors.Translational cancer research · 2025Article
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Authors and funding
20 authors.
Funding
Abstract
backgroundDuring targeted treatment, HER2-positive breast cancers invariably lose HER2 DNA amplification. In contrast, and interestingly, HER2 proteins may be either lost or gained. To longitudinally and systematically appreciate complex/discordant changes in HER2 DNA/protein stoichiometry, HER2 DNA copy numbers and soluble blood proteins (aHER2/sHER2) were tested in parallel, non-invasively (by liquid biopsy), and in two-dimensions, hence HER2-2D.
methodsaHER2 and sHER2 were assessed by digital PCR and ELISA before and after standard-of-care treatment of advanced HER2-positive breast cancer patients (n=37) with the antibody-drug conjugate (ADC) Trastuzumab-emtansine (T-DM1).
resultsAs expected, aHER2 was invariably suppressed by T-DM1, but this loss was surprisingly mirrored by sHER2 gain, sometimes of considerable entity, in most (30/37; 81%) patients. This unorthodox split in HER2 oncogenic dosage was supported by reciprocal aHER2/sHER2 kinetics in two representative cases, and an immunohistochemistry-high status despite copy-number-neutrality in 4/5 available post-T-DM1 tumor re-biopsies from sHER2-gain patients. Moreover, sHER2 was preferentially released by dying breast cancer cell lines treated in vitro by T-DM1. Finally, sHER2 gain was associated with a longer PFS than sHER2 loss (mean PFS 282 vs 133 days, 95% CI [210-354] vs [56-209], log-rank test p=0.047), particularly when cases (n=11) developing circulating HER2-bypass alterations during T-DM1 treatment were excluded (mean PFS 349 vs 139 days, 95% CI [255-444] vs [45-232], log-rank test p=0.009).
conclusionsHER2 gain is adaptively selected in tumor tissues and recapitulated in blood by sHER2 gain. Possibly, an increased oncogenic dosage is beneficial to the tumor during anti-HER2 treatment with naked antibodies, but favorable to the host during treatment with a strongly cytotoxic ADC such as T-DM1. In the latter case, HER2-gain tumors may be kept transiently in check until alternative oncogenic drivers, revealed by liquid biopsy, bypass HER2. Whichever the interpretation, HER2-2D might help to tailor/prioritize anti-HER2 treatments, particularly ADCs active on aHER2-low/sHER2-low tumors.
trial registrationNCT05735392 retrospectively registered on January 31, 2023 https://www. CLINICALTRIALS: gov/search?term=NCT05735392.
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