Abstract P2-08-11: How reliable are biomarkers assessed on a core needle biopsy? A study of paired core needle biopsies and surgical specimens in early breast cancer
Authors: Saghir Hani , Veerla Srinivas , Malmberg Martin , Rydén Lisa , Ehinger Anna , Saal Lao , Vallon-Christersson Johan , Borg Åke , Hegardt Cecilia , Hedenfalk Ingrid , Dieroff-Hay Susanne , Larsson Christer , Loman Niklas , Kimbung Siker 
Published: March 2022

Abstract
Background: The conventional biomarkers estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, and Nottingham histologic grade (NHG) are used to classify breast cancer into its molecular subtypes, determine prognosis, and guide treatment. A preoperative core needle biopsy (CNB) is used to confirm the diagnosis and invasiveness of a breast lesion and forms the basis for characterizing the tumor in the case of neoadjuvant primary treatment, emphasizing the importance of obtaining reliable biomarker assessment from a diagnostic CNB. Aim: The aim of this study was to determine the similarity between biomarker status assessed on a CNB compared to a medically untreated surgical specimen. Methods: Paired CNB and surgical specimens from 267 patients that were part of the prospective Sweden Cancerome Analysis Network- Breast (SCAN-B) cohort were studied. The concordance for the five biomarkers: ER, PgR, Ki67, HER2 and molecular subtype, between paired CNB and surgical specimen were investigated using immunohistochemistry (IHC) and gene expression-based analytical methods (GEX). IHC data were collected from patient medical records and gene expression was measured by RNA sequencing. Cohen’s kappa and Mcnemar’s test were used to compare the concordance of biomarkers.Results: Moderate to very good levels of concordance were observed between the biomarker status obtained on a CNB compared with the paired surgical specimen for IHC (κappa range 0.474-0.917) and GEX (κappa range 0.528-0.776), respectively. However, a significant drift from low to high Ki67 status and from negative to positive HER2 status between the CNB and surgical specimen was observed when using IHC and GEX, respectively (McNemar p &lt; 0.05 for both comparisons). Moderate to good concordance levels of biomarker status were generally obtained when comparing GEX and IHC status measured from the same type of sample (κappa range 0.484-0.649) except for Ki67 which consistently displayed poor concordance levels between IHC and GEX for both CNB and surgical specimen comparisons (κappa range 0.158-0.198). Notably, a significant shift from positive to negative ER status and high to low Ki67 status was observed when comparing IHC with GEX classification (McNemar p &lt;0.001 for both comparisons). Conclusion: The tissue sampling and the method of biomarker analysis may affect the results of biomarker status and ultimately affect treatment decisions. The implications of using a preoperative CNB to determine biomarker status, prognosis, and treatment choice should be taken into consideration in neoadjuvant treatment settings.
Citation Format: Hani Saghir, Srinivas Veerla, Martin Malmberg, Lisa Rydén, Anna Ehinger, Lao Saal, Johan Vallon-Christersson, Åke Borg, Cecilia Hegardt, Ingrid Hedenfalk, Susanne Dieroff-Hay, Christer Larsson, Niklas Loman, Siker Kimbung. How reliable are biomarkers assessed on a core needle biopsy? A study of paired core needle biopsies and surgical specimens in early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-11.