The utility of mitotic index, oestrogen receptor and Ki-67 measurements in the creation of novel prognostic indices fornode-negative breast cancer

Clahsen, P. C.; Velde, Cornelis J.H. van de; Duval, Christian; Pallud, C.; Mandard, A.M.; Delobelle-Deroide, A; Broek, L. van den; Vijver, Marc J. van de

doi:10.1053/ejso.1999.0657

Cited by 85 publications

(53 citation statements)

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“…The same negative results that we found were reported in the literature in 7 of 12 studies concerning patient age, [45][46][47][48][49][50][51] in 9 of 22 studies concerning lymph node status, 45,47,50 -56 in 7 of 19 studies concerning tumor size, 45,47,49,51,54,57,58 and in 4 of 5 studies concerning p21. 59 -62 Our results were at odds with reports in the literature, including 12 of 12 studies that showed positive correlations were between Ki-67 and mitotic activity 45,47,54,[62][63][64][65][66][67][68][69][70] and 8 of 9 studies that showed a correlation between Ki-67 and SPF. 49,53,[65][66][67][71][72][73] The same results that we produced were reported in the literature concerning Scarff-Bloom grade in 23 of 23 reports, 45-51,53-56,58,65,69 -71,73-79 concerning p53 in 12 of 14 reports, 48,54,58,65,72,75,77,80 -84 and concerning hormone receptor status in 19 of 24 reports.…”

Section: Discussioncontrasting

confidence: 57%

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Michels

Duigou

Marescaux

et al. 2003

Cancer

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BACKGROUNDBetween January 11, 1991 and January 8, 1992, 104 patients with previously untreated, invasive, primitive breast carcinoma were admitted to the authors' hospital.METHODSFor each patient, flow cytometry DNA analyses on frozen samples and on immunohistochemical staining were performed, including Ki‐67, cyclin A, p53, and p21waf1 (p21), with assessment of the percentages of positive nuclei were assessed. Correlations with classic clinicopathologic data and survival (overall, metastasis free, or recurrence free) and a multivariate analysis were performed.RESULTSAfter a multivariate analysis according to a Cox model that was stratified by age, tumor size, tumor grade, lymph node status, and receptor status, among the factors studied, the presence of p21 was the unique remaining prognostic factor for patients with invasive breast carcinoma. Because of the lack of a correlation between p21 and proliferative factors (Ki‐67, S‐phase, and cyclin A), the authors combined p21 with those markers and found that, for the different combinations, after statistical analysis, only p21 combined with S‐phase or with cyclin A and lymph node status were salient survival prognostic factors.CONCLUSIONSImmunohistochemical study of proteins involved in the cell cycle and assessment of proliferative activity using flow cytometric DNA analysis aided the authors in singling out correlations of cyclin A and S‐phase, along with p21, with metastasis free survival and overall survival in patients with invasive breast carcinoma. These promising results will require confirmation in a larger series of patients. Cancer 2003;97:1376–86. © 2003 American Cancer Society.DOI 10.1002/cncr.11209

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Section: Discussioncontrasting

confidence: 57%

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Michels

Duigou

Marescaux

et al. 2003

Cancer

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“…However, ligand-binding assay has been replaced by immunohistochemistry on archival tissue over the past several years. Several recent studies have shown that assessing ER by immunohistochemistry is as good as or better than the ligand-binding assay, [10][11][12][13] but similar validation studies for PR are lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Panel of experts at College of American Pathologists, American Society of Clinical Oncology, and National Institute of Health in their last consensus statements had several reservations about assessing ER and PR by immunohistochemistry and noted a lack of standardized and validated assays. 3,4,9 Although a few validated immunohistochemistry methodologies have been published for ER, [10][11][12][13][14] none exist for PR. The few published studies that have assessed PR by immunohistochemistry consisted of patients of mixed clinical stages and variable treatment, making it impossible to separate the prognostic effects from the predictive value of PR.…”

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confidence: 99%

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

et al. 2004

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Progesterone receptor is a surrogate marker of estrogen receptor activity in breast cancer and its utility in helping predict clinical outcome has been established using biochemical assays. However, most laboratories worldwide have switched to immunohistochemistry to assess progesterone receptor, but unfortunately no validated immunohistochemical assay exists for progesterone receptor. The purpose of this study was to develop and validate an immunohistochemical assay for progesterone receptor in breast cancer. The assay was based on monoclonal antibody 1294 (DakoCytomation) and slides were scored microscopically using the 'Allred score' on a scale of 0-8. The assay was compared to ligand-binding assay in 1235 breast cancers, and a subset (n ¼ 362) that received only hormonal therapy was used to define a cutoff for progesterone receptorpositive. Clinical utility was validated in an independent set of samples (n ¼ 423) from a clinical trial randomizing premenopausal breast cancer patients to tamoxifen þ oophorectomy vs observation following surgery. A cutoff of 42 (corresponding to 41% positive cells) dichotomized patients with significantly better or worse clinical outcome (P ¼ 0.0014). Progesterone receptor by immunohistochemistry provided significantly better results than progesterone receptor by ligand-binding assay in predicting clinical outcome. In the clinical trial, a positive result in univariate analyses was associated with significantly improved disease-free and overall survival both in untreated (hazard ratios/P ¼ 0.656/0.060 and 0.479/0.005, respectively) and hormonally treated patients (hazard ratios/P ¼ 0.529/0.017 and 0.451/0.007, respectively). Positive progesterone receptor remained significant for improved disease-free and overall survival (hazard ratios/P ¼ 0.666/0.038 and 0.549/0.007, respectively) in multivariate analyses including the standard variables of tumor size, nodal status, treatment, histological grade, and HER-2/neu status. Estrogen and progesterone receptors are codependent variables and progesterone receptor was a weaker predictor of response to endocrine therapy than estrogen receptor when both were included in multivariate analysis. This is the first comprehensive study assessing the clinical usefulness of progesterone receptor by immunohistochemistry in archival tissue in breast cancer. Progesterone receptor assessed by immunohistochemistry provides useful information about clinical outcome and it is better than progesterone receptor measured by ligand-binding assay.

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“…Therefore, the constant cut-off point is crucial when considering the prognosis for breast cancer patients of all subtypes. moreover, many studies have adopted a cut-off point of 20% (10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer

Nishimura

Osako

Okumura

et al. 2010

Experimental and Therapeutic Medicine

137

102

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Abstract. the choice of adjuvant systemic therapy is based on targeted therapy in line with the St. Gallen consensus meeting. in addition to the traditional parameters, the panel recommended the use of proliferation markers and multigene assays. the purpose of the present study was to evaluate the clinical significance of proliferative activity using the Ki-67 index as a prognostic marker and as a predictor of recurrence time in breast cancer patients. The Ki-67 index was measured in 3,652 cases with primary breast cancer from 1987 to 2009. Out of these patients, 2,638 cases were evaluated simultaneously for estrogen receptor, progesterone receptor and hEr2 from 1997, and these were analyzed as a prognostic factor according to their subtypes. The Ki-67 index exhibited a wide range of 1-99%, with a median of 20%, and cases were divided into 2 or 3 index groups; <20% and ≥20% (and ≥50%). The median Ki-67 index of tumors with luminal A was 17%, and that of luminal B type tumors was 29%. The Ki-67 index of HER2 tumors was 40% and that of triple negative tumors was 50%. A higher Ki-67 index significantly correlated with a higher grade of malignancy. Patients with a higher Ki-67 index had significantly lower disease-free survival (DFS) and overall survival rates. Moreover, there was a significant difference in the recurrence time. multivariate analysis revealed that the Ki-67 index was a significant factor for DFS, irrespective of nodal status, and that Ki-67 was a significant marker only in luminal A type tumors. Furthermore, luminal A type cases with high Ki-67 had a similar DFS as the luminal B type cases. A higher Ki-67 index (≥20%) significantly correlated with other biological markers, poorer prognosis and early recurrence, particularly in luminal a type tumors. it is important to take the Ki-67 index into consideration in the treatment and follow-up of breast cancer patients. Introductionrecently, research on the biology of breast cancer has made surprising progress. an attempt to understand the unique biological characteristics of individual tumors to facilitate treatment has been realized. At present, treatment strategy is, not only based on the stage classification, but also on tumor biology. the St. Gallen international Expert consensus on the primary therapy of early breast cancer outlines the guidelines for endocrine and chemotherapy treatment (1). The treatment allocation mainly consists of targeted treatments, such as endocrine therapy for estrogen receptor (ER)-positive tumors and anti-hEr2 therapy for hEr2-positive tumors. chemotherapy is recommended for triple negative (TN) tumors that have no targets. at present, the vital problem is how to incorporate chemotherapy into the treatment of hormone-sensitive patients with Er-positive and hEr2-negative tumors, as they make up the majority of the patients with primary breast cancer. One solution is to consider the Ki-67 index when deciding the method of treatment.Ki-67 is present in all proliferating cells, and there is great interest in its role as a pro...

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The utility of mitotic index, oestrogen receptor and Ki-67 measurements in the creation of novel prognostic indices fornode-negative breast cancer

Cited by 85 publications

References 4 publications

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer

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