How Reliable Are Gene Expression-Based and Immunohistochemical Biomarkers Assessed on a Core-Needle Biopsy? A Study of Paired Core-Needle Biopsies and Surgical Specimens in Early Breast Cancer

Hani Saghir, Srinivas Veerla, Martin Malmberg, Lisa Rydén, Anna Ehinger, Lao H Saal, Johan Vallon-Christersson, Åke Borg, Cecilia Hegardt, Christer Larsson, Alaa Haidar, Ingrid Hedenfalk, Niklas Loman, Siker Kimbung, Hani Saghir, Srinivas Veerla, Martin Malmberg, Lisa Rydén, Anna Ehinger, Lao H Saal, Johan Vallon-Christersson, Åke Borg, Cecilia Hegardt, Christer Larsson, Alaa Haidar, Ingrid Hedenfalk, Niklas Loman, Siker Kimbung

Abstract

In early breast cancer, a preoperative core-needle biopsy (CNB) is vital to confirm the malignancy of suspected lesions and for assessing the expression of treatment predictive and prognostic biomarkers in the tumor to choose the optimal treatments, emphasizing the importance of obtaining reliable results when biomarker status is assessed on a CNB specimen. This study aims to determine the concordance between biomarker status assessed as part of clinical workup on a CNB compared to a medically untreated surgical specimen. Paired CNB and surgical specimens from 259 patients that were part of the SCAN-B cohort were studied. The concordance between immunohistochemical (IHC) and gene expression (GEX) based biomarker status was investigated. Biomarkers of interest included estrogen receptor (ER; specifically, the alpha variant), progesterone receptor (PgR), Ki67, HER2, and tumor molecular subtype. In general, moderate to very good correlation in biomarker status between the paired CNB and surgical specimens was observed for both IHC assessment (83-99% agreement, kappa range 0.474-0.917) and GEX assessment (70-97% agreement, kappa range 0.552-0.800), respectively. However, using IHC, 52% of cases with low Ki67 status in the CNB shifted to high Ki67 status in the surgical specimen (McNemar's p = 0.011). Similarly, when using GEX, a significant shift from negative to positive ER (47%) and from low to high Ki67 (16%) was observed between the CNB and surgical specimen (McNemar's p = 0.027 and p = 0.002 respectively). When comparing biomarker status between different techniques (IHC vs. GEX) performed on either CNBs or surgical specimens, the agreement in ER, PgR, and HER2 status was generally over 80% in both CNBs and surgical specimens (kappa range 0.395-0.708), but Ki67 and tumor molecular subtype showed lower concordance levels between IHC and GEX (48-62% agreement, kappa range 0.152-0.398). These results suggest that both the techniques used for collecting tissue samples and analyzing biomarker status have the potential to affect the results of biomarker assessment, potentially also impacting treatment decisions and patient survival outcomes.

Keywords: breast cancer; core-needle biopsy; genomic profiling; immunohistochemistry.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart showing the selection of the study specific cohort (n = 259) from the SCAN-B cohort.
Figure 2
Figure 2
Concordance of St Gallen subtypes (A) and PAM50 subtypes (B) between paired core-needle biopsies and surgical specimens.
Figure 3
Figure 3
Gene Set Enrichment Analysis (GSEA) for RNAseq profiles between paired CNBs and surgical specimens. Examples of histograms showing the distribution of the Hallmark of cancer pathways enriched among genes showing significantly higher expression in CNBs compared with the paired surgical specimens. Refer to Supplementary Table S3 for the full list of the enriched Hallmark of cancer pathways among the genes with higher expression in CNBs compared with surgical specimens.
Figure 4
Figure 4
Gene Set Enrichment Analysis (GSEA) of RNAseq profiles between paired CNBs and surgical specimens. Examples of histograms showing the distribution of the Hallmark of cancer pathways enriched among genes showing significantly lower expression in CNBs compared with the paired surgical specimens. Refer to Supplementary Table S3 for the full list of the enriched Hallmark of cancer pathways among the genes with lower expression in CNBs compared with surgical specimens.

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