Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison With the Genomic Health Recurrence Score in Early Breast Cancer

Cuzick, Jack; Dowsett, Mitch; Pineda, Sílvia; Wale, Chris; Salter, Janine; Quinn, Emma M.; Zabaglo, Lila; Mallon, Elizabeth; Green, Andrew; Ellis, Ian O.; Howell, Anthony; Buzdar, Aman U.; Forbes, John F.

doi:10.1200/jco.2010.31.2835

Cited by 660 publications

(653 citation statements)

References 13 publications

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“…8,16,17,30 Furthermore, an immunohistochemical panel of ER, PR, HER2, and Ki67 in conjunction with standard clinicopathological parameters (IHC4 score) has been shown to provide similar prognostic information to the recurrence score in hormone receptor-positive patients treated with endocrine therapy. 31 Integration of such an immunohistochemical panel into routine practice would merely require the addition of Ki67 to the pathologist's workload. Unfortunately, Ki67 immunohistochemistry poses a number of challenges including (i) definition of a clinically relevant cut point, (ii) the impact of intratumoral heterogeneity, and (iii) the appropriateness of using the most proliferative area or the average proliferation rate.…”

Section: Lp Feeley Et Almentioning

confidence: 99%

Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

et al. 2014

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The objectives of this study were to determine the prognostic significance of subgrouping estrogen receptor (ER)-positive breast tumors into low-and high-risk luminal categories using Ki67 index, TP53, or progesterone receptor (PR) status. The study group comprised 540 patients with lymph node negative, invasive breast carcinoma. Luminal A subtype was defined as being ER positive, HER2 negative, and Ki67 low (o14% cells positive) and luminal B subtype as being ER positive, HER2 negative, and Ki67 high (Z14% cells positive). Luminal tumors were also subgrouped into risk categories based on the PR and TP53 status. Survival analysis was performed. Patients with luminal B tumors (n ¼ 173) had significantly worse disease-free survival compared to those with luminal A tumors (n ¼ 186) (log rank P-value ¼ 0.0164; univariate Cox regression relative risk 2.00; 95% CI, 1.12-3.58; P ¼ 0.0187). Luminal subtype remained an independent prognostic indicator on multivariate analysis including traditional prognostic factors (relative risk 2.12; 95% CI, 1.16-3.88; P ¼ 0.0151). Using TP53 status or PR negativity rather than Ki67 to classify ER-positive luminal tumors gave similar outcome results to those obtained using the proliferation index. However, it was a combination of the three markers, which proved the most powerful prognostically. Ki67 index, TP53 status, or PR negativity can be used to segregate ERpositive, HER2-negative tumors into prognostically meaningful subgroups with significantly different clinical outcomes. These biomarkers particularly in combination may potentially be used clinically to guide patient management.

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Section: Lp Feeley Et Almentioning

confidence: 99%

Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

et al. 2014

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“…New drugs, better chemotherapy (CT) schemes, and the use of monoclonal antibodies on HER2 over expressing tumors (Burstein et al, 2012) explain major advances on its treatment. Knowledge of BC heterogeneity has also enabled personalize the treatment, thus BC subtype (Goldhirsch et al, 2011) affects the prognosis of the disease, and the possibility of response to endocrine therapy (ET) and CT. Intrinsic subtypes defined initially through genetic-molecular studies, are associated with certain subtypes characterized by classic histopathological parameters (Paik et al, 2004;Cuzick et al, 2011;Goldhirsch et al, 2011;Tang et al, 2011;The Cancer Genome Atlas Research Network 2012) and defined as: Luminal: phenotypically characterized by ER expression; HER2 positive: showing HER2 over expression without ER expression and TN: negative for ER, PR and HER2 (Goldhirsch et al, 2011;Reis-Filho et al, 2011). Ki67 is a nuclear protein, expressed by proliferating cells in late G1, S and G2 / M cell cycle phases; reflecting the proportion of proliferating cells and has been used as a predictor of response to ET and in recent studies, to CT. Ki67 expression, as determined by IHC, also allows to subdivide the Luminal subtype in A and B (Pathmanathan et al, 2013) (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

Petric

Martínez²,

Acevedo³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). Conclusions: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

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“…30 More recent studies using IHC4 assay (ER, PR, HER2, and Ki-67) and Magee Equations have also emphasized the important role of PR levels in ERpositive breast cancer. 87,88 Most recently, data from a study with more than 9000 patients with an 8-year follow up indicated that combining Ki-67 and PR levels could better separate luminal B subtype from luminal A subtype. 28 The authors defined luminal A as ER þ , HER2 À , and Ki-67 of less than 14% with any PR, or Ki-67 of 14% to 19% with PR greater than 20%; and luminal B as ER þ , HER2 À , and Ki-67 of greater than 14% with any PR, or Ki-67 of 14% to 19% and PR less than 20%.…”

Section: Ihc-based MC Er-positive Bcmentioning

confidence: 99%

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

Tang¹,

Tse

2016

Archives of Pathology &Amp; Laboratory Medicine

124

109

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Context.-The pioneering works on molecular classification (MC) by Perou and Sorlie et al in the early 2000s using global gene expression profiling identified 5 intrinsic subtypes of invasive breast cancers (IBCs): luminal A, luminal B, normal breast-like, HER2-enriched, and basallike subtypes, each unique in incidence, survival, and response to therapy. Because the application of gene expression profiling in daily practice is not economical or practical at the present time, many investigators have studied the use of immunohistochemical (IHC) surrogates as a substitute for determining the MC of IBC.Objective.-To discuss the continuing efforts that have been made to develop clinically significant and readily available IHC surrogates for the MC of IBC.Data Sources.-Data were obtained from pertinent peer-reviewed English-language literature.Conclusions.-The most commonly used IHC surrogates are estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), dividing IBC into luminal, HER2, and triple-negative subtypes. The addition of Ki-67, cytokeratin 5, and epidermal growth factor receptor (EGFR) separates luminal B from luminal A subtypes, and basal-like subtype from triple-negative breast cancer. More recently, biomarkers such as androgen receptor and p53 have been shown to further stratify these molecular subtypes. Although many studies of IHC-based MC have shown clinical significance similar to gene expression profiling-defined MC, its critical limitations are: (1) a lack of standardization in terminology, (2) a lack of standardization in biomarkers used for each subtype, and (3) the lack of a uniform cutoff for each biomarker. A panel of IHC surrogates for each subtype of IBC is proposed.

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Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison With the Genomic Health Recurrence Score in Early Breast Cancer

Abstract: This study suggests that the amount of prognostic information contained in four widely performed IHC assays is similar to that in the GHI-RS. Additional studies are needed to determine the general applicability of the IHC4 score.

Cited by 660 publications

References 13 publications

Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

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