Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Apr;174(3):795-805.
doi: 10.1007/s10549-018-05119-2. Epub 2019 Jan 18.

Re-testing of predictive biomarkers on surgical breast cancer specimens is clinically relevant

Stephanie Robertson  1   2 , Caroline Rönnlund  3   4 , Jana de Boniface  5   6 , Johan Hartman  3   4   7
Affiliations

Re-testing of predictive biomarkers on surgical breast cancer specimens is clinically relevant

Stephanie Robertson et al. Breast Cancer Res Treat. 2019 Apr.

Abstract

Purpose: The accuracy of predictive and prognostic biomarker assessment in breast cancer is paramount since these guide therapy decisions. The aim was to investigate the concordance of biomarkers and immunohistochemical (IHC)-based surrogate tumor subtypes between core needle biopsies (CNB) and consecutive paired breast cancer surgical resections.

Methods: This retrospective study comprised two cohorts of patients with primary breast cancer diagnosed between 2016 and 2017: one treated with primary surgery (n = 526) and one with neoadjuvant chemotherapy (NAC) (n = 216). The agreement between preoperative CNB and paired tumor specimens regarding the assessment of biomarkers and surrogate tumor subtypes was evaluated in both cohorts.

Results: In the primary surgery cohort, the concordance rates and kappa values for estrogen receptor (ER), progesterone receptor (PR) and Ki67 were 98.6% (κ = 0.917), 89.3% (κ = 0.725) and 78.8% (κ = 0.529), respectively. Importantly, human epidermal growth factor receptor 2 (HER2) IHC assessment showed only moderate agreement (κ = 0.462). HER2 status combining IHC and in situ hybridization was discordant in 3.6% of cases, potentially impacting on indications for HER2-targeted therapy. The concordance rate for IHC-based surrogate tumor subtypes was only 73.2-78.3%. Generally lower concordance rates for ER, PR and HER2 were observed in the NAC cohort. Here, HER2 status was discordant in 7.4%.

Conclusions: The agreement of HER2 and Ki67 between CNB and paired surgical specimen in primary breast cancer is insufficient. Limited agreement of surrogate tumor subtypes indicates a significant clinical value of biomarker re-testing on surgical specimens.

Keywords: Breast cancer; Core biopsy; Human epidermal growth factor receptor 2; Immunohistochemistry; Ki67; Predictive biomarker.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

JH is scientific advisor of Visiopharm AG and has obtained advisory board fees from AstraZeneca and Novartis, honoraria and speakers bureau from Roche AB. The other authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Research Ethics Committee at Karolinska Institutet, Stockholm, Sweden) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

The study was based on retrospective clinical data, and no additional patient consent was required in accordance to ethical approval. However, prior to surgery, all patients have approved storage of material in the Stockholm Medical Biobank for clinical and research purposes.

Figures

Fig. 1
Fig. 1
Sankey diagrams for immunohistochemical (IHC)-based surrogate tumor subtype re-classification in core needle biopsy (CNB) versus paired surgical specimen (SS) in the primary surgery cohort. Surrogate tumor subtype re-classification according to St. Gallen definitions (a) and Swedish guideline definitions (b)
Fig. 2
Fig. 2
Sankey diagrams for immunohistochemical (IHC)-based surrogate tumor subtype re-classification in core needle biopsy (CNB) versus paired surgical specimen (SS) in the NAC cohort according to definitions by St. Gallen (a) and Swedish guidelines (b)
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lonning PE, Borresen-Dale AL. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98(19):10869–10874. doi: 10.1073/pnas.191367098. - DOI - PMC - PubMed
    1. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–752. doi: 10.1038/35021093. - DOI - PubMed
    1. Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, Quackenbush JF, Stijleman IJ, Palazzo J, Marron JS, Nobel AB, Mardis E, Nielsen TO, Ellis MJ, Perou CM, Bernard PS. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160–1167. doi: 10.1200/JCO.2008.18.1370. - DOI - PMC - PubMed
    1. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100(14):8418–8423. doi: 10.1073/pnas.0932692100. - DOI - PMC - PubMed
    1. Guiu S, Michiels S, Andre F, Cortes J, Denkert C, Di Leo A, Hennessy BT, Sorlie T, Sotiriou C, Turner N, Van de Vijver M, Viale G, Loi S, Reis-Filho JS. Molecular subclasses of breast cancer: how do we define them? The IMPAKT 2012 working group statement. Ann Oncol. 2012;23(12):2997–3006. doi: 10.1093/annonc/mds586. - DOI - PubMed

MeSH terms