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.
Highlights
Patients and methodsReliable determination of molecular subtype is indispensable for prognostication and treatment decision in breast cancer (BC) [1, 2]
When applying a cutoff point of core needle biopsy (CNB) Ki67 labeling index (Ki67-LI) < 20% for luminal A” (LumA) molecular subtype, 152 of 195 LumA cases were diagnosed correctly and 43 tumors were falsely classified as luminal B” (LumB) by CNB
Two hundred thirty-four out of 289 LumB cases were correctly classified as Ki67-LI ≥ 20%, and 55 cases were falsely classified as LumA by CNB (Fig. 1b)
Summary
Reliable determination of molecular subtype is indispensable for prognostication and treatment decision in breast cancer (BC) [1, 2]. In estrogen receptor (ER)– positive and human epidermal growth factor 2 (HER2)– negative luminal BC, assessment of molecular subtype is of critical prognostic importance [3,4,5,6,7,8,9]. Reproducible and clinically valid Ki67-LI determination in core needle biopsy (CNB) might be biased by technical difficulties, assessment methods, or intratumoral heterogeneity. No universal Ki67-LI cutoff levels to define molecular subtype in luminal BC are specified, and discrepancies regarding implications on clinical decisions persist [1, 17,18,19]. Whereas cutoff values can be statistically validated, the influence of intratumoral heterogeneity on the reliability of Ki67-LI in CNB remains to be resolved
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Virchows Archiv : an international journal of pathology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
