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Comparative Study
. 2024 May 29;25(11):5910.
doi: 10.3390/ijms25115910.

Comparing the HER2 Status of the Primary Tumor to That of Disseminated Tumor Cells in Early Breast Cancer

Léa Louise Volmer  1 , Dominik Dannehl  1 , Sabine Matovina  1 , Florin-Andrei Taran  2 , Christina Barbara Walter  1 , Markus Wallwiener  3 , Sara Yvonne Brucker  1 , Andreas Daniel Hartkopf  1 , Tobias Engler  1
Affiliations
Comparative Study

Comparing the HER2 Status of the Primary Tumor to That of Disseminated Tumor Cells in Early Breast Cancer

Léa Louise Volmer et al. Int J Mol Sci. .

Abstract

Breast cancer remains a leading cause of cancer mortality in women globally. Despite advancements in systemic therapy, the risk of distant recurrence persists even after such treatment and may be linked to disseminated tumor cells (DTCs). Variability in molecular characteristics between primary tumors (PTs) and distant metastases underscores the need to comprehensively understand metastatic pathways. This retrospective study investigated discrepancies between HER2 expression in PTs and DTCs and their implications for survival outcomes in 201 early breast cancer (EBC) patients. We found a significant association between HER2 expression in PTs and DTCs when classifying tumors as HER2-high/low/negative. Patients whose HER2 status was discordant between PTs and DTCs exhibited worse distant disease-free survival than those with concordant status. Multivariate analysis confirmed the HER2 status of DTCs as an independent prognostic factor for distant DFS. These findings emphasize the importance of assessing HER2 expression in DTCs and its potential implications for tailored therapy strategies in EBC. Furthermore, prospective trials are needed to validate these findings and explore targeted therapies based on the molecular characteristics of DTCs.

Keywords: breast cancer; disseminated tumor cells; minimal residual disease; targeted therapy.

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Conflict of interest statement

Markus Wallwiener has received personal fees for consulting or advisory services from Roche, Novartis, AstraZeneca, Amgen, Pfizer, MSD Oncology, Lilly, and funding for travel and accommodation expenses from Roche and MSD. Florin-Andrei Taran has received speaker and consultancy honoraria from Astra Zeneca, Exact Sciences, Gilead, GSK, MSD, Novartis, Onkowissen, Pfizer, Roche research grant: Exact Sciences. All other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Sankey diagram of HER2 classification of the primary tumor (“classical” and “modern *”) and of HER2 status of DTCs. * modern: HER2-low was defined as HER2 IHC 1+ or IHC 2+ without FISH or CISH amplified, HER2-high as HER2 IHC 3+ or IHC 2+ with FISH or CISH amplified, and HER2-negative as HER2 IHC 0.
Figure 2
Figure 2
Kaplan–Meier plots of overall survival (OS) (A), disease-free survival (DFS) (B), distant disease-free survival (dDFS) (C), and cancer-specific survival (CSS) (D) according to HER2 status of DTCs.
Figure 3
Figure 3
Kaplan–Meier plots of overall survival (OS) (A), disease-free survival (DFS) (B), distant disease-free survival (doffs) (C), and cancer-specific survival (CSS) (D) according to consistency of HER2 status between PT and DTCs.
See this image and copyright information in PMC

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