Factors influencing agreement of breast cancer luminal molecular subtype by Ki67 labeling index between core needle biopsy and surgical resection specimens

Abstract Reliable determination of Ki67 labeling index (Ki67-LI) on core needle biopsy (CNB) is essential for determining breast cancer molecular subtype for therapy planning. However, studies on agreement between molecular subtype and Ki67-LI between CNB and surgical resection (SR) specimens are conflicting. The present study analyzed the influence of clinicopathological and sampling-associated factors on agreement. Molecular subtype was determined visually by Ki67-LI in 484 pairs of CNB and SR specimens of invasive estrogen receptor (ER)–positive, human epidermal growth factor (HER2)–negative breast cancer. Luminal B disease was defined by Ki67-LI > 20% in SR. Correlation of molecular subtype agreement with age, menopausal status, CNB method, Breast Imaging Reporting and Data System imaging category, time between biopsies, type of surgery, and pathological tumor parameters was analyzed. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. CNB had a sensitivity of 77.95% and a specificity of 80.97% for identifying luminal B tumors in CNB, compared with the final molecular subtype determination after surgery. The correlation of Ki67-LI between CNB and SR was moderate (ROC-AUC 0.8333). Specificity and sensitivity for CNB to correctly define molecular subtype of tumors according to SR were significantly associated with tumor grade, immunohistochemical progesterone receptor (PR) and p53 expression (p < 0.05). Agreement of molecular subtype did not significantly impact RFS and OS (p = 0.22 for both). The identified factors likely mirror intratumoral heterogeneity that might compromise obtaining a representative CNB. Our results challenge the robustness of a single CNB-driven measurement of Ki67-LI to identify luminal B breast cancer of low (G1) or intermediate (G2) grade.

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Factors Influencing Agreement Between Core Needle Biopsy and Surgical Resection Specimens Regarding KI67 Labeling Index – Results of a Retrospective Analysis

Annals of Oncology ◽

10.1093/annonc/mdt078.3 ◽

2013 ◽

Vol 24 ◽

pp. iii13

Author(s):

Z. Bago-Horvath ◽

F. Rössler ◽

P. Wimmer ◽

K. Pinker-Domenig ◽

R. Bartsch ◽

...

Keyword(s):

Retrospective Analysis ◽

Surgical Resection ◽

Core Needle Biopsy ◽

Needle Biopsy ◽

Labeling Index ◽

Core Needle ◽

Ki67 Labeling Index ◽

Factors Influencing

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Abstract P5-02-10: Factors influencing agreement of Ki67 labeling index between core needle biopsy and surgical resection specimens

10.1158/1538-7445.sabcs14-p5-02-10 ◽

2015 ◽

Author(s):

Zsuzsanna Bago-Horvath ◽

Fabian Roessler ◽

Philipp Wimmer ◽

Martina Mittlboeck ◽

Nicolas Kozakowski ◽

...

Keyword(s):

Surgical Resection ◽

Core Needle Biopsy ◽

Needle Biopsy ◽

Labeling Index ◽

Core Needle ◽

Ki67 Labeling Index ◽

Factors Influencing

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Intra- and inter-observer variability in tumor infiltrating lymphocyte scoring in breast cancer core needle biopsy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12626 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12626-e12626

Author(s):

Klara Geršak ◽

Barbara Gazic ◽

Andreja Klevisar Ivancic ◽

Nina Ruzic Gorenjec ◽

Cvetka Grasic Kuhar

Keyword(s):

Breast Cancer ◽

Core Needle Biopsy ◽

Working Group ◽

Needle Biopsy ◽

Intraclass Correlation ◽

Observer Variability ◽

Acceptable Error ◽

Core Needle ◽

Luminal B ◽

Inter Observer Variability

e12626 Background: Morphological evaluation of tumor lymphocyte infiltration (TIL) in breast cancer (BC) is gaining importance in the clinical setting, as it provides good prognostic information. Most institutions adhere to TIL working group guidelines for evaluating TIL, while having to settle on an acceptable error margin due to its subjective nature, which leads to intra and inter-observer scoring discordance. We aimed to analyze both at our institution, using experienced and inexperienced examiners, with a continuous variable scoring system. Methods: 209 BC core needle biopsy (CNB) samples were stained using hematoxylin-eosin. The percentage of stromal TIL was scored using a numerical variable ranging from 1 to 100. The examination group consisted of two experienced pathologists (pathologist A and B) and one inexperienced examiner - a medical oncology resident with a learning process containing study of the TIL working group analysis criteria and about 100 samples analysed together with an experienced pathologist Pathologist A and the resident analyzed the study samples twice, pathologist B once. Intraclass correlation coefficient (ICC) was used to measure overall intra and inter-observer agreement. Statistical analysis was performed using Google Sheets and Python. Results: 203 CNB samples were analysed (6 were excluded due to inadequate quality or an inconclusive diagnosis). Patients were aged 26 to 79 years (median 49). Sample size ranged from 1 to 16 mm (median 8). The proportion of BC subtypes was: luminal A-like 18%, luminal B-like 39%, HER2+ 10%, luminal B-like HER2+ 12%, TNBC 18%, not defined 2%. The highest proportion of high stromal TIL (≥50%) was seen in HER2+ (30%) and TNBC (22%) subtypes, as observed by pathologist A. We found good intra and inter-observer ICC (Table). Conclusions: Acceptable intra and inter-observer variability was observed in experienced pathologists, suggesting that the proposed methodology could reliably be used in clinical practice, research and trials. Interestingly, variability analysis of scores from a trained non-pathologist has also produced good results. However, it is important to note that inexperienced scoring could be prone to errors, for example counting non-lymphocyte cells as such, not recognizing regions of necrosis or sample damage, or not distinguishing between the tumor and peripheral stroma. Intraclass correlation: two-way random, single score (ICC2); pathologist A and resident (R) first and second analysis (A1, A2, R1, R2); pathologist B analysis (B1). Interpretation of ICC: <0.50 poor; 0.50-0.75 moderate; 0.75-0.90 good (0.75 = minimal acceptable value for a reliable clinical measurement); >0.90 excellent. Clinical trial information: 2018-000547-11. [Table: see text]

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