Concordance between core needle biopsy and surgical excision specimens for Ki‐67 in breast cancer – a systematic review of the literature

Kalvala, Jahnavi; Parks, Ruth M.; Green, Andrew; Cheung, Kwok-Leung

doi:10.1111/his.14555

Cited by 10 publications

(9 citation statements)

References 59 publications

(227 reference statements)

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“…Additional support for the conclusion that the difference in Ki67 between CB and WS is provided by the observation of clinically relevant differences between specimens in cases from different institutions used in this study, independently scored multiple times by 17 pathologists. Although many studies focused on assessing the level of agreement between CB and resection samples in Ki67 scoring; consensus was not possible due to lack of standardization 32 .…”

Section: Discussionmentioning

confidence: 99%

Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study

Mahboubi-Ardakani¹,

Dowsett²,

Dowsett³

et al. 2022

Modern Pathology

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Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error (p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections (p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor.

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Section: Discussionmentioning

confidence: 99%

Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study

Mahboubi-Ardakani¹,

Dowsett²,

Dowsett³

et al. 2022

Modern Pathology

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“…Recently, Zhang et al also confirmed the heterogeneity in HER2-Low breast cancers by using another two similar microarray-based genomic profile analyses, MammaPrint and BluePrint [ 17 ]. In addition, the technical aspects of HER2 testing methods are likely a major reason for the HER2 discrepancy [ 8 , 31 ]. According to the current guidelines, the IHC/FISH test is a reliable tool to differentiate HER2-Positive tumors from HER2-Negative tumors [ 32 ], while the lower boundary of HER2-Low diagnosis seems to be more confusing.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, the method of sampling also has a great influence on the HER2 expression test. CNB is a minimally invasive preoperative examination for early diagnosis and (neo)adjuvant strategy decision making, but the relatively small amount of biopsy tissue available for examination is an inevitable restriction for an accurate result [ 31 ]. Although previous research has demonstrated the high accuracy of ER, PR, Ki67 and HER2 as dichotomous variables ( Supplementary Table S3 ), our current study showed a relatively lower concordance rate in HER2-Low status diagnosis by CNB; thus, retesting HER2 status with a larger sample size after radical surgery could provide a more precise diagnosis, especially for HER2-Low status detection.…”

Section: Discussionmentioning

confidence: 99%

HER2-Low Status Is Not Accurate in Breast Cancer Core Needle Biopsy Samples: An Analysis of 5610 Consecutive Patients

Zhu

Tong

et al. 2022

Cancers

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Background: HER2-Low status is found in approximately half of breast cancer patients and shows potential benefits from novel antibody–drug conjugates (ADCs). Data on the accuracy of HER2-Low status between core needle biopsy (CNB) and surgical excision specimen (SES) samples are lacking. We aimed to investigate the accuracy of HER2-Low status diagnosis between CNB and SES samples. Methods: Consecutive early-stage breast cancer patients who underwent surgery from January 2009 to March 2022 with paired CNB and SES samples were retrospectively reviewed. HER2-Low was defined as IHC 1+ or IHC2+ and FISH-negative. Concordance rates were analyzed by the Kappa test. Further clinicopathological characteristics were compared among different HER2 status and their changes. Results: A total of 5610 patients were included, of whom 3209 (57.2%) and 3320 (59.2%) had HER2-Low status in CNB and SES samples, respectively. The concordance rate of HER2 status in the whole population was 82.37% (Kappa = 0.684, p < 0.001), and was 76.87% in the HER2-Negative patients (Kappa = 0.372, p < 0.001). Among 1066 HER2-0 cases by CNB, 530 patients were classified as HER2-Low tumors. On the contrary, in 3209 patients with HER2-Low tumor by CNB, 387 were scored as HER2-0 on the SES samples. ER-negative or Ki67 high expression tumor by CNB had a high concordance rate of HER2-Low status. Conclusions: A relatively low concordance rate was found when evaluating HER2-Low status between CNB and SES samples in HER2-Negative breast cancer patients, indicating the necessity of retesting HER2 low status at surgery, which may guide further therapy in the era of anti-HER2 ADCs.

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“…For patients initially treated by surgery, the task force recommends testing a core biopsy when possible, but a whole well-fixed section from untreated breast tissue is an acceptable alternative. There is a high but not perfect concordance between paired core biopsies and whole sections from resection specimens, with the scores being systematically higher in core biopsies, possibly due to more controlled preanalytical variables [ 22 , 23 , 24 ]. Tissue fixed in alcohol-based fixatives, often used in cytology preparation, as well as decalcified tissue, should be avoided.…”

Section: Questions To Addressmentioning

confidence: 99%

Ki67 in Breast Cancer Assay: An Ad Hoc Testing Recommendation from the Canadian Association of Pathologists Task Force

et al. 2023

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Ki67, a marker of cellular proliferation, is commonly assessed in surgical pathology laboratories. In breast cancer, Ki67 is an established prognostic factor with higher levels associated with worse long-term survival. However, Ki67 IHC is considered of limited clinical use in breast cancer management largely due to issues related to standardization and reproducibility of scoring across laboratories. Recently, both the American Food and Drug Administration (FDA) and Health Canada have approved the use of abemaciclib (CDK4/6 inhibitor) for patients with HR+/HER2: high-risk early breast cancers in the adjuvant setting. Health Canada and the FDA have included a Ki67 proliferation index of ≥20% in the drug monograph. The approval was based on the results from monarchE, a phase III clinical trial in early-stage chemotherapy-naïve, HR+, HER2 negative patients at high risk of early recurrence. The study has shown significant improvement in invasive disease-free survival (IDFS) with abemaciclib when combined with adjuvant endocrine therapy at two years. Therefore, there is an urgent need by the breast pathology and medical oncology community in Canada to establish national guideline recommendations for Ki67 testing as a predictive marker in the context of abemaciclib therapy consideration. The following recommendations are based on previous IKWG publications, available guidance from the monarchE trial and expert opinions. The current recommendations are by no means final or comprehensive, and their goal is to focus on its role in the selection of patients for abemaciclib therapy. The aim of this document is to guide Canadian pathologists on how to test and report Ki67 in invasive breast cancer. Testing should be performed upon a medical oncologist’s request only. Testing must be performed on treatment-naïve tumor tissue. Testing on the core biopsy is preferred; however, a well-fixed resection specimen is an acceptable alternative. Adhering to ASCO/CAP fixation guidelines for breast biomarkers is advised. Readout training is strongly recommended. Visual counting methods, other than eyeballing, should be used, with global rather than hot spot assessment preferred. Counting 100 cells in at least four areas of the tumor is recommended. The Ki67 scoring app developed to assist pathologists with scoring Ki67 proposed by the IKWG, available for free download, may be used. Automated image analysis is very promising, and laboratories with such technology are encouraged to use it as an adjunct to visual counting. A score of <5 or >30 is more robust. The task force recommends that the results are best expressed as a continuous variable. The appropriate antibody clone and staining protocols to be used may take time to address. For the time being, the task force recommends having tonsils/+pancreas on-slide control and enrollment in at least one national/international EQA program. Analytical validation remains a pending goal. Until the data become available, using local ki67 protocols is acceptable. The task force recommends participation in upcoming calibration and technical validation initiatives.

show abstract

Concordance between core needle biopsy and surgical excision specimens for Ki‐67 in breast cancer – a systematic review of the literature

Cited by 10 publications

References 59 publications

Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study

Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study

HER2-Low Status Is Not Accurate in Breast Cancer Core Needle Biopsy Samples: An Analysis of 5610 Consecutive Patients

Ki67 in Breast Cancer Assay: An Ad Hoc Testing Recommendation from the Canadian Association of Pathologists Task Force

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