Abstract P5-08-34: Concordance of histologic grade of invasive breast cancer between core needle biopsy and surgical excision specimen; A systematic review and meta-analysis
Authors: Knuttel FM , Menezes GLG , van Diest PJ , van den Bosch MAAJ , Verkooijen HM 
Published: May 2016

Abstract
Introduction
Histologic grade is one of the most important prognostic factors for breast cancer and one of the determinants of the need for adjuvant systemic treatment. Grading is usually based on surgical excision (SE) specimen. However, with the increasing use of neoadjuvant chemotherapy and minimally invasive ablative therapies, pre-treatment assessment of grade is needed. Core needle biopsy (CNB) is an accurate tool for diagnosing breast cancer. It is unclear whether CNB provides sufficient tissue for accurate grading. We conducted a systematic review and meta-analysis of the literature to derive a reliable estimate of the agreement in grading between CNB and SE.
Methods
This study was conducted according to the Preferred method for Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) criteria. A search in EMBASE, PubMed and the Cochrane Library was conducted. Studies that provided data on grade of both CNB and SE were included. Proportion of agreement between CNB and SE, agreement beyond chance (Cohen's kappa) and the proportion of over- and underestimation of CNB grading were calculated for each study and pooled. Agreement of grade components (tubular formation, nuclear pleomorphism and mitotic rate), was also pooled. Random effect models were applied because of substantial heterogeneity (tested by I2 test). Meta-regression was used to explore determinants of the level of agreement between CNB and SE.
Results
The search retrieved 1232 papers, of which 34 articles were included in the systematic review (6029 patients) and 33 studies were used for meta-analysis (4980 patients). Pooled absolute agreement was 71.1% (95%CI 68.9-73.3%), pooled Cohen's kappa was 0.54 (95%CI 0.5-0.58). Underestimation of grading by CNB occurred more frequently than overestimation; 19.1% (95%CI 17.1-21.3%) and 9.3% (95%CI 7.7-11.4%), respectively. Fourteen studies reported nuclear pleomorphism scores, with a pooled agreement of 70.2% (95%CI 65.7-74.3%). Pooled agreement of tubule formation (12 studies) was 74.5% (95%CI 68.4-79.5%). For mitotic count (13 studies), pooled agreement was 62.4% (95%CI 57-67.6%). Meta-regression showed a positive association between agreement of histologic type on CNB and SE and agreement of grading. Higher proportion of ER positive patients was negatively associated with agreement.
Conclusions and discussion
Grading on CNB corresponds moderately with grading on SE. CNB underestimates grade in one of five patients. Of the three grade components, mitotic count is most frequently disconcordant. However, incorrect tumor grading does not have clinical implications in all patients, since the indication for adjuvant systemic therapy is decided by several other factors as well and in a substantial proportion of cases not affected by differences in grade. Finally, considerable inter-observer variability of grading on only SE exists, which may also affect treatment decision making.
Citation Format: Knuttel FM, Menezes GLG, van Diest PJ, van den Bosch MAAJ, Verkooijen HM. Concordance of histologic grade of invasive breast cancer between core needle biopsy and surgical excision specimen; A systematic review and meta-analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-34.