Preoperative core needle biopsy is accurate in determining molecular subtypes in invasive breast cancer

Abstract

BackgroundEstrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 have been increasingly evaluated by core needle biopsy (CNB) and are recommended for classifying breast cancer into molecular subtypes. However, the concordance rate between CNB and open excision biopsy (OEB) has not been well documented.MethodsPatients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive.ResultsThere were 298 invasive breast cancer patients analyzed. Concordance rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67 expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P = 0.046). Good agreement (κ = 0.658) was demonstrated in evaluating molecular subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%. However, using a cut-point of Ki67 either 14% or 20% for both specimens, there will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and Luminal B on OEB.ConclusionCNB was accurate in determining ER, PgR, and HER2 status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67 should be retested on OEB samples in HR+/HER2- patients to accurately distinguish Luminal A from B tumors.

Prediction of Response to Neoadjuvant Chemotherapy Using Core Needle Biopsy Samples with the Prosigna Assay

“…Variability in the Pearson correlation coefficients for the various components of the ROR score did not exceed 0.10 ( Table 2). Given that the SD for the ROR score within multiple RNA extractions of the same CNB is similar to that reported for ROR score within an SRS (17), we hypothesize that the increased variance observed across multiple CNBs of the same tumor is likely due to molecular heterogeneity within the tumor tissue (18,19).…”

“…Our results show that the tumor tissue requirements for performing Prosigna in CNBs are practical in daily clinical practice (19). All the CNBs evaluated in this portion of the study were from retrospective diagnostic specimens that had already been used for standard histopathologic workup including determination of the status of ER, PR, HER2, and Ki67.…”

“…Identification of Basal-like disease within ER-positive breast cancer has been previously reported (21). Considering the differences in precision between multiple biopsies from a single tumor and multiple extractions from a single biopsy, these discordant results likely reflect intratumoral heterogeneity (18,19).…”

“…The observed increase in variability is likely due to different areas of the tumor being biopsied (i.e., intratumor heterogeneity; refs. 18,19). It is also possible that the quality of a subset of the biopsy pairs was biased with regard to tissue quality (e.g., more or less normal tissue contamination).…”

Standardized Assessment of Ki-67 in Breast Cancer Patients Using Virtual Slides and an Automated Analyzer in Comparison to Central/Local Pathological Assessments

“…However, there are certain limitations to the Ki-67 index, including standardization of a measurement method, reproducibility of measurement results, and establishment of cut-off values [13][14][15][16]. The core needle biopsy (CNB) procedure is almost as accurate as immunohistochemical analysis of surgical specimens for breast cancer diagnosis and is now widely accepted as the standard diagnostic procedure [17][18][19][20]. However, previous reports have shown variations in Ki-67 expression among pretreatment CNB specimens and post-treatment surgical specimens [21][22][23].…”