Ki‐67 expression in breast carcinoma

Trihia, Helen; Murray, Susan; Price, Karen N.; Gelber, Richard D.; Golouh, Rastko; Goldhirsch, Aron; Coates, Alan S.; Collins, John P.; Castiglione‐Gertsch, Monica; Gusterson, Barry A.

doi:10.1002/cncr.11188

Cited by 164 publications

(57 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The potential use of MIB-1 expression in the definition of a tumor grading system with a greater clinical utility has recently been suggested (21). We assessed the impact of MIB-1 expression on the risk of Lymph node metastasis in different grade subgroups amongst our patients and found a strong difference between MIB-1-negative and -positive cases in grade-2 tumors.…”

Section: -------------------------------------------------mentioning

confidence: 96%

Mib-1 proliferation index is an independent predictor of lymph node metastasis in invasive breast cancer: A prospective study on 675 patients

Marrelli

Pinto²,

Neri³

et al. 2006

Oncol Rep

View full text Add to dashboard Cite

Abstract. In order to evaluate the potential risk factors for Lymph node metastasis in invasive breast cancer patients submitted to axillary dissection, 675 patients who received surgery between January 1995 and December 2002 were included in a prospective study. In all cases, MIB-1 proliferation index was investigated by immunohistochemistry. Lymph node involvement was found in 248 out of 675 patients. Univariate analysis showed that peritumoral lymphovascular invasion, pT stage, tumor multiplicity, MIB-1 proliferation index >10%, oestrogen receptor status, histological type, tumor grade and progesterone receptor status were related to a higher incidence of Lymph node metastasis, with various levels of statistical significance. Multivariate analysis identified lymphovascular invasion [relative risk (RR, 7.69; p<0.001), pT stage (RR, 3.08; p<0.001), tumor multiplicity (RR, 3.89; p<0.001), and MIB-1 proliferation index (RR, 1.66; p=0.019)] as independent predictive variables. The impact of MIB-1 positivity on the incidence of Lymph node metastasis was particularly evident in intermediate risk groups (pT1c, pT2 without lymphovascular invasion), as well as in grade-2 tumors. In conclusion, the MIB-1 proliferation index could provide additional information about the risk of Lymph node metastasis in invasive breast cancer, and may be useful to identify grade-2 tumors with a more aggressive clinical behaviour. IntroductionNodal status is a strong prognostic factor in breast cancer and is one of the most important variables considered in deciding on adjuvant treatment after surgery. Sentinel node biopsy, although not the standard of care, is rapidly becoming widely accepted as an alternative staging procedure for the axilla in breast cancer. However, in subgroups of patients with a high risk of Lymph node metastasis, this procedure may not provide a clinical benefit and may involve a waste of resources as, in a high percentage of cases, it is followed by axillary dissection. The definition of tumor characteristics that are predictive of Lymph node metastasis may be useful in order to better select which patients to submit to axillary surgery (1).Besides commonly used pathological factors, cell proliferation has an important role as an indicator of biological aggressiveness in breast cancer. Ki-67 antibody reacts with a nuclear antigen which is present in G1, S, G2 phases and mitosis but is absent in G0 and is therefore considered a marker of the proliferative activity of the tumor (2). Unfortunately, the epitope that recognizes Ki-67 is destroyed in the fixation and paraffin embedding process. More recently, the MIB-1 antibody, which recognizes Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, has been described and applied to breast cancer (3,4).Several studies have investigated the role of the proliferation index in breast cancer patients and a strong correlation between the MIB-1 labelling index and Lymph node metastasis has been reported (5,6), although this finding has not been confirmed by others (7-10)....

show abstract

Section: -------------------------------------------------mentioning

confidence: 96%

Mib-1 proliferation index is an independent predictor of lymph node metastasis in invasive breast cancer: A prospective study on 675 patients

Marrelli

Pinto²,

Neri³

et al. 2006

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…Unsurprisingly, given that the Nottingham grading system defines mitotic rate as one of its three criteria (Trihia et al 2003), there is a good correlation with tumor grade. The relationship with ER has been predominantly described as an inverse correlation with lower proliferative activity in ER-positive tumors (Haerslev et al 1996).…”

Section: Emerging Biomarkers Ki67mentioning

confidence: 99%

Current and emerging biomarkers in breast cancer: prognosis and prediction

Weigel¹,

Dowsett²

2010

Endocrine-Related Cancer

416

296

View full text Add to dashboard Cite

Breast cancer treatment has experienced several changes in the past decades due to the discovery of specific prognostic and predictive biomarkers that enable the application of more individualized therapies to different molecular subgroups. These subgroups show specific differences regarding biological clinical behavior. In addition to the classical clinical prognostic factors of breast cancer, established molecular biomarkers such as estrogen receptor and progesterone receptor have played a significant role in the selection of patients benefiting from endocrine therapy for many years. More recently, the human epidermal growth factor receptor 2 (HER2) has been validated to be not only a prognostic factor, but also a predictor of response to HER2 targeting therapy. The shift toward an earlier diagnosis of breast cancer due to improved imaging methods and screening programs highlights the need for new factors and combinations of biomarkers to quantify the residual risk of patients and to indicate the potential value of additional treatment strategies. The marker of proliferation Ki67 has recently emerged as an important marker due to several applications in neoadjuvant therapy in addition to its moderate prognostic value. With the introduction of high-throughput technologies, numerous multigene signatures have been identified that aim to outperform traditional markers: current prospective clinical trials are seeking evidence for their definitive role in breast cancer. There exist many more factors and approaches that have the potential to become relevant in the near future including the detection of single disseminating and circulating tumor cells in blood and bone marrow as well as of circulating cell-free DNA and microRNA. Careful randomized prospective testing and comparison with existing established factors will be required to select those emerging markers that offer substantial cost-effective benefit and thereby justify their routine use for breast cancer therapy decision-making.

show abstract

“…For practical purposes, in order to reliably distinguish between 'luminal A' (more endocrine-sensitive, more indolent and better prognosis) and 'luminal B (HER2-negative)' (less endocrine-sensitive, more aggressive and worse prognosis) Breast cancers expressing high levels of Ki67, which is a nuclear marker of cell proliferation, are associated with worse outcomes (8)(9)(10). However, a standard operating procedure has not been established, and the inter-laboratory and inter-study comparabilities of Ki67 are limited (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of Ki67 and p53 in patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer: Validation of the cut-off value of the Ki67 labeling index as a predictive factor

Ohara

Matsuura

Akimoto

et al. 2016

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. The aim of this study was to evaluate the significance of the Ki67 labeling index and p53 status as prognostic and predictive indicators of operable estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Among 697 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2013, 308 patients with ER-positive and HER2-negative breast cancer were assessed. The results of the multivariate Cox analysis demonstrated that a high Ki67 labeling index was significantly associated with a short recurrence-free interval (RFI) (P=0.004) and was marginally associated with a worse overall survival (P= 0.074). A positive p53 status was not associated with worse outcomes. To validate the cut-off values of the Ki67 labeling index for identifying patients who may benefit from additional chemotherapy, prognostic factors were investigated in breast cancer patients treated postoperatively with endocrine therapy alone. Analysis of receiver operating characteristic curves demonstrated that a Ki67 labeling index cut-off of 20.0% was optimal for predicting recurrence among patients who did not receive adjuvant chemotherapy. The 5-year RFIs for patients with Ki67 <20 and ≥20% were 97.2 and 86.6%, respectively (P= 0.0244). A high Ki67 labeling index (≥20%) was significantly associated with large tumors (P<0.01), lymph node metastasis (P=0.0236) and positive p53 status (P<0.001). The univariate analysis demonstrated that Ki67 labeling index ≥20%, lymph node metastasis and progesterone receptor negativity were significant worse prognostic factors for RFI (P=0.0333, 0.0116 and 0.0573, respectively). The Ki67 labeling index was found to be a useful prognostic factor in patients with ER-positive and HER2-negative breast cancer and the cut-off values of the Ki67 labeling index for making a decision regarding adjuvant treatment were validated. IntroductionFor the majority of patients with early breast cancer, adjuvant systemic therapy is recommended following primary surgery to reduce the risk of breast cancer recurrence and to increase the likelihood of a cure. Approximately 70% of breast cancers express estrogen receptor (ER), and ER status is a powerful predictor of response to therapies that inhibit estrogen synthesis or block the action of its receptor (1). Endocrine therapies are established in the adjuvant setting (2-4). It is important to distinguish patients with ER-positive tumors at high risk for recurrence who require additional chemotherapy, from those for whom adjuvant endocrine therapy alone may suffice, as the economic burden and toxicities of chemotherapy must be minimized (5). Multi-gene assays are strong candidate tools for predicting the risk of recurrence in ER-positive patients (6). However, classification using multi-gene expression analyses is not appropriate for everyday practice. According to the St. Gallen Consensus Conference held in 2013, the intrinsic subtype affects the indication for adjuvant chemotherapy and surrogat...

show abstract

Ki‐67 expression in breast carcinoma

Cited by 164 publications

References 65 publications

Mib-1 proliferation index is an independent predictor of lymph node metastasis in invasive breast cancer: A prospective study on 675 patients

Mib-1 proliferation index is an independent predictor of lymph node metastasis in invasive breast cancer: A prospective study on 675 patients

Current and emerging biomarkers in breast cancer: prognosis and prediction

Prognostic value of Ki67 and p53 in patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer: Validation of the cut-off value of the Ki67 labeling index as a predictive factor

Contact Info

Product

Resources

About