Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer

Robertson, Stephanie; Stålhammar, Gustav; Darai‐Ramqvist, Eva; Rantalainen, Mattias; Tobin, Nicholas P.; Bergh, Jonas; Hartman, Johan

doi:10.1136/jclinpath-2017-204976

Cited by 26 publications

(21 citation statements)

References 38 publications

(14 reference statements)

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“…The proliferation activity of tumours is usually determined with immunohistochemical detection of the cell‐cycle‐specific antigen Ki‐67. Some studies have proved that Ki‐67 expression is a useful prognostic factor in breast cancer . Our results also indicated that Ki‐67 status in post‐operative pathology IHC was the significant prognostic factor, and patients with low SII would have survive longer than those with high SII by Ki‐67 status.…”

Section: Discussionsupporting

confidence: 65%

Pre‐treatment systemic immune‐inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy

Chen

Kong

Wang

et al. 2020

J Cellular Molecular Medi

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The systemic immune‐inflammation index (SII = N × P/L) based on neutrophil (N), platelet (P) and lymphocyte (L) counts is used to predict the survival of patients with malignant tumours and can fully reflect the balance between host inflammatory and immune status. This study is conducted to explore the potential prognostic significance of SII in patients with breast cancer undergoing neoadjuvant chemotherapy (NACT). A total of 262 patients with breast cancer received NACT were enrolled in this study. According to the receiver operating characteristic curve, the optimal cut‐off value of SII was divided into two groups: low SII group (<602 × 109/L) and high SII group (≥602 × 109/L). The associations between breast cancer and clinicopathological variables by SII were determined by chi‐squared test or Fisher's exact test. The Kaplan‐Meier plots and log‐rank test were used to determine clinical outcomes of disease‐free survival (DFS) and overall survival (OS). The prognostic value of SII was analysed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by National Cancer Institute Common Toxicity Criteria (NCICTC). According to univariate and multivariate Cox regression survival analyses, the results showed that the value of SII had prognostic significance for DFS and OS. The patients with low SII value had longer DFS and OS than those with high SII value (31.11 vs 40.76 months, HR: 1.075, 95% CI: 0.718‐1.610, P = .006; 44.47 vs 53.68 months, HR: 1.051, 95% CI: 0.707‐1.564, P = .005, respectively). The incidence of DFS and OS in breast cancer patients with low SII value was higher than that in those patients with high SII value in 3‐, 5‐ and 10‐year rates. The common toxicities after NACT were haematological and gastrointestinal reaction, and there were no differences by SII for the assessment of side effects of neoadjuvant chemotherapy. Meanwhile, the results also proved that breast cancer patients with low SII value and high Miller and Payne grade (MPG) survived longer than those breast cancer with high SII value and low MPG grade. In patients without lymph vessel invasion, these breast cancer patients with low SII value had better prognosis and lower recurrence rates than those with high SII value. Pre‐treatment SII with the advantage of reproducible, convenient and non‐invasive was a useful prognostic indicator for breast cancer patients undergoing neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

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Section: Discussionsupporting

confidence: 65%

Pre‐treatment systemic immune‐inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy

Chen

Kong

Wang

et al. 2020

J Cellular Molecular Medi

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“…In our study, we also examined the Ki-67-score in ER − tumors, and did not observe any substantial differences in this when comparing recurrent cases and controls. Our results are in line with the variability seen in other studies, 45 and underline the complexity and well-known challenges of using the Ki-67 index as a biomarker in clinical decision-making. 46 , 47 …”

Section: Discussionsupporting

confidence: 91%

<p>Digital Image Analysis of Ki-67 Stained Tissue Microarrays and Recurrence in Tamoxifen-Treated Breast Cancer Patients</p>

Egeland¹,

Jónsdóttir²,

Lauridsen³

et al. 2020

CLEP

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The proliferation marker Ki-67 has been used as a prognostic marker to separate low-and high-risk breast cancer subtypes and guide treatment decisions for adjuvant chemotherapy. The association of Ki-67 with response to tamoxifen therapy is unclear. Highthroughput automated scoring of Ki-67 might enable standardization of quantification and definition of clinical cutoff values. We hypothesized that digital image analysis (DIA) of Ki-67 can be used to evaluate proliferation in breast cancer tumors, and that Ki-67 may be associated with tamoxifen resistance in early-stage breast cancer. Patients and Methods: Here, we apply DIA technology from Visiopharm using a custom designed algorithm for quantifying the expression of Ki-67, in a case-control study nested in the Danish Breast Cancer Group clinical database, consisting of stages I, II, or III breast cancer patients of 35-69 years of age, diagnosed during 1985-2001, in the Jutland peninsula, Denmark. We assessed DIA-Ki-67 score on tissue microarrays (TMAs) from breast cancer patients in a case-control study including 541 ER-positive and 300 ER-negative recurrent cases and their non-recurrent controls, matched on ER-status, cancer stage, menopausal status, year of diagnosis, and county of residence. We used logistic regression to estimate odds ratios and associated 95% confidence intervals to determine the association of Ki-67 expression with recurrence risk, adjusting for matching factors, chemotherapy, type of surgery, receipt of radiation therapy, age category, and comorbidity. Results: Ki-67 was not associated with increased risk of recurrence in tamoxifen-treated patients (ORadj =0.72, 95% CI 0.54, 0.96) or ER-negative patients (ORadj =0.85, 95% CI 0.54, 1.34). Conclusion: Our findings suggest that Ki-67 digital image analysis in TMAs is not associated with increased risk of recurrence among tamoxifen-treated ER-positive breast cancer or ER-negative breast cancer patients. Overall, our findings do not support an increased risk of recurrence associated with Ki-67 expression.

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“…Sampling different tumor regions as with CNBs may therefore affect biomarker agreement as seen in the present study. Low concordance in biomarker status has also been identified between aspiration cytology and histology-based assessments as a sign of sampling error [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Re-testing of predictive biomarkers on surgical breast cancer specimens is clinically relevant

Robertson

Rönnlund

Boniface

et al. 2019

Breast Cancer Res Treat

Self Cite

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Purpose The accuracy of predictive and prognostic biomarker assessment in breast cancer is paramount since these guide therapy decisions. The aim was to investigate the concordance of biomarkers and immunohistochemical (IHC)-based surrogate tumor subtypes between core needle biopsies (CNB) and consecutive paired breast cancer surgical resections. Methods This retrospective study comprised two cohorts of patients with primary breast cancer diagnosed between 2016 and 2017: one treated with primary surgery ( n = 526) and one with neoadjuvant chemotherapy (NAC) ( n = 216). The agreement between preoperative CNB and paired tumor specimens regarding the assessment of biomarkers and surrogate tumor subtypes was evaluated in both cohorts. Results In the primary surgery cohort, the concordance rates and kappa values for estrogen receptor (ER), progesterone receptor (PR) and Ki67 were 98.6% ( κ = 0.917), 89.3% ( κ = 0.725) and 78.8% ( κ = 0.529), respectively. Importantly, human epidermal growth factor receptor 2 (HER2) IHC assessment showed only moderate agreement ( κ = 0.462). HER2 status combining IHC and in situ hybridization was discordant in 3.6% of cases, potentially impacting on indications for HER2-targeted therapy. The concordance rate for IHC-based surrogate tumor subtypes was only 73.2–78.3%. Generally lower concordance rates for ER, PR and HER2 were observed in the NAC cohort. Here, HER2 status was discordant in 7.4%. Conclusions The agreement of HER2 and Ki67 between CNB and paired surgical specimen in primary breast cancer is insufficient. Limited agreement of surrogate tumor subtypes indicates a significant clinical value of biomarker re-testing on surgical specimens.

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Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer

Cited by 26 publications

References 38 publications

Pre‐treatment systemic immune‐inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy

Pre‐treatment systemic immune‐inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy

<p>Digital Image Analysis of Ki-67 Stained Tissue Microarrays and Recurrence in Tamoxifen-Treated Breast Cancer Patients</p>

Re-testing of predictive biomarkers on surgical breast cancer specimens is clinically relevant

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