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.

• Authors: Kristina A Tendl-Schulz, Fabian Rössler, Philipp Wimmer, Ulrike M Heber, Martina Mittlböck, Nicolas Kozakowski, Katja Pinker, Rupert Bartsch, Peter Dubsky, Florian Fitzal, Martin Filipits, Fanny Carolina Eckel, Eva-Maria Langthaler, Günther Steger, Michael Gnant, Christian F Singer, Thomas H Helbich, Zsuzsanna Bago-Horvath
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 477 Issue 4 Pg. 545-555 (Oct 2020) ISSN: 1432-2307 [Electronic] Germany
• PMID: 32383007 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Ki-67 Antigen
• MKI67 protein, human
• Receptors, Estrogen
• Receptors, Progesterone
• TP53 protein, human
• Tumor Suppressor Protein p53
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Biopsy, Large-Core Needle
• Breast Neoplasms (chemistry, pathology, surgery)
• Disease Progression
• Female
• Humans
• Immunohistochemistry
• Ki-67 Antigen (analysis)
• Middle Aged
• Neoplasm Grading
• Neoplasm Recurrence, Local
• Predictive Value of Tests
• Progression-Free Survival
• Receptor, ErbB-2 (analysis)
• Receptors, Estrogen (analysis)
• Receptors, Progesterone (analysis)
• Reproducibility of Results
• Retrospective Studies
• Risk Factors
• Time Factors
• Tumor Suppressor Protein p53 (analysis)