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

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.

Analysis of the molecular subtypes of preoperative core needle biopsy and surgical specimens in invasive breast cancer

“…Identifying HER2-positive breast cancer patients by CNB is important, as neoadjuvant HER2-targeted therapy is an effective option for these patients. In this study, the CR for HER2 status, as determined by HER2 IHC or reflex HER2 SISH, was as high as 99.7% (kappa, 0.988), which was higher than most previous reports (ranging from 61%-97.3%) [10,[18][19][20][21][22][23][24][25][26][27][28][29]. The reason for this high CR could partially be due to performing reflex HER2 SISH for all HER2 IHC equivocal cases to determine final HER2 status strictly following ASCO/CAP guidelines.…”

Estrogen, progesterone, and human epidermal growth factor receptor 2 discordance between primary and metastatic breast cancer

“…Several studies reported varying concordance of results between the surgical specimen and core needle biopsy of ER (77.8 to 99%), PR (69 to 97%), and HER2 (64 to 97%), respectively, with particular emphasis placed on a general tendency for higher discrepancies in PR status [22][23][24][25][26][27]. In addition to substantial improvement in receptor measurement accuracy, interlaboratory variation still exists in the assignment of receptor status [28,29].…”

HER2 positive breast cancer patients having HER2 loss after neoadjuvant chemotherapy should still be treated with adjuvant anti-HER2 treatment

“…I want to congratulate Robertson and their colleagues for their article [1] in which they investigated the concordance of biomarkers and immunohistochemical (IHC)-based surrogate tumor subtypes between core needle biopsies (CNB) and consecutive paired breast cancer surgical resections. This retrospective study comprised two cohorts of patients with primary breast cancer: one treated with primary surgery (n = 526) and one with neoadjuvant chemotherapy (NAC) (n = 216).…”