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

Abstract

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...

Comparative study of Her-2, p53, Ki-67 expression and clinicopathological characteristics of breast cancer in a cohort of northern China female patients

“…39,40 Ki-67 is a nuclear protein that is commonly used for the detection and quantification of proliferating cells. 28 In agreement with the observations by others, 35,50,51 it was found that Ki-67 positively connected with Her-2 overexpression in this study, suggesting that Her-2 overexpression might upregulate the expression of Ki-67.…”

“…37 Ki-67 is a nuclear protein that is commonly used for the detection and quantification of proliferating cells because an increase in its expression is associated with cell growth. 27 Consistent with the observations of others, 6,37,[50][51][52][53] our observation that Ki-67 positive led breast carcinoma progress to higher histological grade in breast patients implicated that Ki-67 high expression promoted tumor growth in breast cancer patients. 50 Our observation that both PR positive and ER positive connected with a slower histological progress in breast cancer, which was in agreement with the observations by Shapochka et al, 37 suggests that PR and ER might have an inhibitive role in breast cancers.…”

“…12 In agreement with the observation by Kobayashi et al, 61 our finding that p53 positive is connected with the progression of carcinoma to a higher histological grade and Her-2 overexpression in breast cancer patients suggests that p53 positive could be used as a prognostic biomarker for breast cancer 56,[62][63][64] in addition to being used as a diagnostic biomarker. 38 Our findings that Ki-67 positive is connected with the progression of carcinoma to a higher histological grade as well as Her-2 overexpression in breast cancer patients are consistent with the previous observations 5,35,50,61 and increase the reliability of this emerging biomarker 38 as a predictor of breast cancer prognosis outcomes. Our observation that both PR positive and ER positive are connected with a slower histological progress and are negatively connected with Her-2 overexpression in breast cancer supports that PR positive and ER positive are good biomarkers for predicting better prognosis and response to endocrine therapy than patients that lacked these receptors.…”

Immunological and molecular genetic characteristics of luminal B breast cancer: a literature review

“…Медиана Ki-67 при люминальном А РМЖ составила 17 %, в то время как при люминальном В -29 %. Данные приведены в таблице, где индекс Ki-67 сопоставлен c молекуляр-ными подтипами РМЖ [25].…”

Mathematical model of cancer growth controled by metronomic chemotherapies

“…(3) On the small part of healthy tissue considered here, the mean oxygen concentration is assumed to be constant in time and space. (4) In the hot spots of a tumor, the part of proliferant cells between tumor cells is of 20 to 30 % [47,54]. (5) Resistance mechanisms make the tumor start growing again after 6 to 8 month in the MTD protocol [27].…”