Conventional and digital Ki67 evaluation and their correlation with molecular prognosis and morphological parameters in luminal breast cancer

Pons, Laura; Hernández-León, Laura; Altaleb, Ahmad; Ussene, Esperança; Iglesias, Roman Garcia-Varela; Castillo, Ana Fernanda; Rodríguez-Martínez, Paula; Castellà, Eva; Quiroga, Vanesa; Felip, E.; Cirauqui, Beatriz; Margelı́, Mireia; Fernández, Pedro

doi:10.1038/s41598-022-11411-5

Cited by 4 publications

(8 citation statements)

References 38 publications

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“…Many studies have shown a decent and significant overall concordance between Ki67 and Oncotype DX or MammaPrint. 24,25 However, like CAB, EPclin also failed to show a significant correlation with Ki67. 25 The reason for such a concordance between Ki67 and Oncotype DX or MammaPrint could be that Ki67 is part of the regression equation that these two tests use, but Ki67 is not a part of either EPclin or CAB.…”

Section: Discussionmentioning

confidence: 94%

“…To our surprise, there was a poor overall agreement between CAB and Ki67 (0–30% as low risk and above as high risk) with κ 0.07 (96% CI: 0.02–0.12). Many studies have shown a decent and significant overall concordance between Ki67 and Oncotype DX or MammaPrint 24,25 . However, like CAB, EPclin also failed to show a significant correlation with Ki67 25 .…”

Section: Discussionmentioning

confidence: 98%

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The usefulness of CanAssist Breast over Ki67 in breast cancer recurrence risk assessment

Eshwaraiah¹,

Gunda²,

Kanakasetty

et al. 2023

Cancer Medicine

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Background: Assessment of Ki67 by immunohistochemistry (IHC) has limited utility in clinical practice owing to analytical validity issues. According to International Ki67 Working Group (IKWG) guidelines, treatment should be guided by a prognostic test in patients expressing intermediate Ki67 range, >5%-<30%. The objective of the study is to compare the prognostic performance of CanAssist Breast (CAB) with that of Ki67 across various Ki67 prognostic groups. Methods:The cohort had 1701 patients. Various risk groups were compared for the distant relapse-free interval (DRFi) derived from Kaplan-Meier survival analysis. As per IKWG, patients are categorized into three risk groups: low-risk (<5%), intermediate risk (>5%-<30%), and high-risk (>30%). CAB generates two risk groups, low and high risk based on a predefined cutoff.Results: In the total cohort, 76% of the patients were low risk (LR) by CAB as against 46% by Ki67 with a similar DRFi of 94%. In the node-negative sub-cohort, 87% were LR by CAB with a DRFi of 97% against 49% by Ki67 with a DRFi of 96%.In subgroups of patients with T1 or N1 or G2 tumors, Ki67-based risk stratification was not significant while it was significant by CAB. In the intermediate Ki67 (>5%-<30%) category up to 89% (N0 sub-cohort) were LR by CAB and the percentage of LR patients was 25% (p < 0.0001) higher compared to NPI or mAOL. In the low Ki67 (≤5%) group, up to 19% were segregated as high-risk by CAB with 86% DRFi suggesting the requirement of chemotherapy in these low Ki67 patients. Conclusion:CAB provided superior prognostic information in various Ki67 subgroups, especially in the intermediate Ki67 group.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 98%

The usefulness of CanAssist Breast over Ki67 in breast cancer recurrence risk assessment

Eshwaraiah¹,

Gunda²,

Kanakasetty

et al. 2023

Cancer Medicine

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“…As expected, 7 studies 10 , 13 , 14 , 16 , 17 , 25 from 2011 through 2018 used the old cutoffs, that is, ODx score of ⩽18 for low risk, 18 to 30 for intermediate risk, and ⩾31 for high risk. Two studies from 2022, 27 , 28 also used the older cutoffs, likely because their patient cohorts were taken from before 2018. Six 18 , 19 , 23 , 26 , 29 , 31 studies used the new cutoffs which categorize <15 as low risk, 16 to 25 as intermediate risk, and ⩾26 as high risk, while 3 studies 20 , 21 , 24 used both criteria for their analyses.…”

Section: Resultsmentioning

confidence: 99%

“… 10 , 16 , 18 , 22 - 24 , 26 , 27 One study used 15 as the cut off albeit without any justification, 14 whereas another determined their own institutional cutoffs (⩽24 for low) based on their patient population. 28 Two studies also used <10 and >25 as cutoffs for low and high Ki-67, respectively. 25 , 31 This heterogeneity in cutoffs indicates an absence of standardization.…”

Section: Resultsmentioning

confidence: 99%

“…Another study concluded that ODx testing could be considered an option for patients with high Ki-67 proliferation index or high-grade tumors because the score might classify them as low risk sparing these individuals’ chemotherapy in HR-positive EBC. 28 Rigorous risk stratification, therefore, is necessary to ensure that the benefits of adjuvant chemotherapy are not withheld, and additional toxicities are not incurred. A major discrepancy in the studies we reviewed was the variation in risk stratification cutoffs for the Ki-67 index.…”

Section: Discussionmentioning

confidence: 99%

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Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature

Mooghal,

Khan,

Samar

et al. 2024

Breast Cancer�(Auckl)

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Background: Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, node-negative, or 1 to 3 lymph node-positive early breast cancers (EBCs). The cost of the test, which is not available in low-middle income countries (LMICs), is not within the means of most individuals. The Ki-67 index is a marker of tumor proliferation that is cost-effective and easily performed and has been substituted in many cases to obtain prognostic information. Objective: We aimed to identify the correlation between the ODx recurrence score (RS) and the Ki-67 index in HR-positive EBCs and to determine whether Ki-67, like the ODx, can help facilitate clinical decision-making. Design: Systematic review correlating Ki-67 index and ODx in HR-positive and HER2-negative EBCs as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data sources and methods: We searched different databases between January 2010 and May 2023 and included retrospective/prospective cohorts, clinical trials, case-control, and cross-sectional studies involving HR-positive and HER2-negative EBCs correlating the Ki-67 index and ODx RS categories. Results: Of the 18 studies included, 16 indicated a positive or weakly positive correlation between ODx and the Ki-67 index. The combined P value of the included studies is <0.05 ( P = .000), which shows a statistical significance between the 2. Our review also discusses the potential of machine learning and artificial intelligence (AI) in Ki-67 assessment, offering a cost-effective and reproducible alternative. Conclusion: Even although there are limitations, studies indicate a favorable association between ODx and the Ki-67 index in specific situations. This implies that Ki-67 can offer important predictive details, especially regarding the likelihood of relapse in HR-positive EBC. This is particularly significant in LMICs where financial constraints often hinder the availability of costly diagnostic tests.

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The Ki67 dilemma: investigating prognostic cut-offs and reproducibility for automated Ki67 scoring in breast cancer

Rewcastle,

Skaland,

Gudlaugsson

et al. 2024

Breast Cancer Res Treat

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Purpose Quantification of Ki67 in breast cancer is a well-established prognostic and predictive marker, but inter-laboratory variability has hampered its clinical usefulness. This study compares the prognostic value and reproducibility of Ki67 scoring using four automated, digital image analysis (DIA) methods and two manual methods. Methods The study cohort consisted of 367 patients diagnosed between 1990 and 2004, with hormone receptor positive, HER2 negative, lymph node negative breast cancer. Manual scoring of Ki67 was performed using predefined criteria. DIA Ki67 scoring was performed using QuPath and Visiopharm® platforms. Reproducibility was assessed by the intraclass correlation coefficient (ICC). ROC curve survival analysis identified optimal cutoff values in addition to recommendations by the International Ki67 Working Group and Norwegian Guidelines. Kaplan–Meier curves, log-rank test and Cox regression analysis assessed the association between Ki67 scoring and distant metastasis (DM) free survival. Results The manual hotspot and global scoring methods showed good agreement when compared to their counterpart DIA methods (ICC > 0.780), and good to excellent agreement between different DIA hotspot scoring platforms (ICC 0.781–0.906). Different Ki67 cutoffs demonstrate significant DM-free survival (p < 0.05). DIA scoring had greater prognostic value for DM-free survival using a 14% cutoff (HR 3.054–4.077) than manual scoring (HR 2.012–2.056). The use of a single cutoff for all scoring methods affected the distribution of prediction outcomes (e.g. false positives and negatives). Conclusion This study demonstrates that DIA scoring of Ki67 is superior to manual methods, but further study is required to standardize automated, DIA scoring and definition of a clinical cut-off.

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Conventional and digital Ki67 evaluation and their correlation with molecular prognosis and morphological parameters in luminal breast cancer

Cited by 4 publications

References 38 publications

The usefulness of CanAssist Breast over Ki67 in breast cancer recurrence risk assessment

The usefulness of CanAssist Breast over Ki67 in breast cancer recurrence risk assessment

Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature

The Ki67 dilemma: investigating prognostic cut-offs and reproducibility for automated Ki67 scoring in breast cancer

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