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. 2025 Sep;213(2):273-279.
doi: 10.1007/s10549-025-07781-9. Epub 2025 Jul 18.

Quantitative assessment of HER2 expression in invasive ductal carcinoma and co-existing DCIS

Haiying Zhan  1 , Nay Nwe Nyein Chan  2 , Revekka Khaimova  2 , Thazin N Aung  2 , Patricia Gaule  2 , Charles J Robbins  2 , David L Rimm  2   3
Affiliations

Quantitative assessment of HER2 expression in invasive ductal carcinoma and co-existing DCIS

Haiying Zhan et al. Breast Cancer Res Treat. 2025 Sep.

Abstract

Purpose: Previous studies have demonstrated that ductal carcinoma in situ (DCIS) component often exhibits higher HER2 expression than the invasive component when assessed by immunohistochemistry, while some other studies showed concordant HER2 expression between these two components. In this study, we used our high-sensitivity HER2 (HS-HER2) quantitative immunofluorescence assay to compare HER2 expression in IDC and co-existing DCIS and correlate with clinicopathologic characteristics.

Methods: We included 36 IDC + DCIS cases from the Yale Pathology department. DCIS was classified according to the three-tier nuclear grading system: low (grade 1), intermediate (grade 2), and high (grade 3) nuclear grade. Invasive carcinoma was graded according to the modified Bloom-Richardson histologic grading system. Cases were divided into two groups: low to intermediate-grade DCIS (G1-2) with co-existing invasive carcinoma (n = 26) and high-grade DCIS (G3) with co-existing invasive carcinoma (n = 10). Separate regions of interest for IDC and DCIS were annotated by two board-certified pathologists. Serial sections of FFPE tumor specimens were used to accurately measure the HER2 protein expression by the HS-HER2 assay in attomole/mm2 unit and the acquisition by QuPath v.04 with the Qymia extension.

Results: Low to intermediate-grade DCIS expressed higher HER2 levels (4295 ± 449 amol/mm2) than co-existing invasive carcinoma (2880 ± 413 amol/mm2). Similarly, high-grade DCIS expressed higher HER2 levels (4953 ± 700 amol/mm2) than co-existing invasive carcinoma (3560 ± 688 amol/mm2). Neither of these trends toward lower expression levels in the IDC were statistically significant. Additionally, no significant statistic difference was noted between low to intermediate-grade DCIS versus high-grade DCIS or between their corresponding co-existing invasive carcinomas in this cohort.

Conclusion: Using the HS-HER2 assay, our results demonstrated comparable HER2 expression levels in DCIS and paired invasive carcinoma regardless of histopathological grade or HER2 immunohistochemical score. These findings contributed to a more nuanced understanding of HER2 biology in early breast carcinogenesis and may inform future biomarker-driven therapeutic strategies.

Keywords: Ductal carcinoma in situ; High sensitivity-HER2 (HS-HER2); Invasive ductal carcinoma; Quantitative immunofluorescence.

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Conflict of interest statement

Declarations. Conflict of interest: Dr. Rimm has served as a Consultant/Advisor to Astra Zeneca, Cell Signaling Technology, Cepheid, Danaher, Halda Therapeutics, Incendia, NextCure, Nucleai, PAIGE.AI, Regeneron, and Sanofi. Astra Zeneca, Cepheid, NavigateBP, NextCure, Danaher/Leica, Regeneron and Konica/Minolta currently fund, or have previously funded, research in his lab. Ethics approval and consent to participate: This study was approved by the IRB at Yale University. This study was retrospective in nature and all information was properly de-identified; therefore, ethics approval and consent were waived.

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