breast cancers ( bcs ) are the most frequent malignancy among women that can be a leading cause of death through middle - aged women . despite the fact that bc is a major health issue , very few studies describe its characteristics in the middle east . bcs can be divided based on their gene expression profiles , into at least four groups : luminal - type , the human epidermal growth factor receptor 2 ( her2)-type , normal - like - type , and basal - type . luminal - type cancers are characterized by an activated estrogen receptor ( er ) signaling pathway and are divided into two subtypes , luminal subtypes  a  and  b  . in general , luminal - subtype - a tumors express higher levels of er and carry a better prognosis than do luminal - subtype - b tumors . er positivity predicts response to endocrine therapy such as antiestrogen ( tamoxifen ) and trastuzumab therapy ( herceptin ) for tumor with her2 overexpression . a number of studies have shown that the immune response of ki-67 is closely associated with the cell cycle . furthermore , ki-67 may predict the pathological remission rate in bc patients following neoadjuvant chemotherapy , as an increased ki-67 level following neoadjuvant chemotherapy indicates a poor prognosis . a meta - analysis involving 12 , 155 patients demonstrated that the ki-67 positivity confers a higher risk of recurrence and a worse survival rate in patients with early bc . even though this meta - analysis could not scrutinize if ki-67 had independent prognostic value beyond the standard clinicopathological variables , it confirmed that the high levels of ki-67 are associated with worse prognoses . the other important biological markers in early bc are tumor size , nuclear grade , axillary lymph node involvement , er , progesterone receptor ( pr ) , and her2 status . uncontrolled proliferation ( such as ki-67 ) is a key characteristic of malignant tumors and , therefore , tumor proliferation is one of the major factors associated with prognosis . the aim of this study was to evaluate the use and value of ki-67 as a prognostic marker in bc and associations between ki-67 , clinical , and histopathological parameters were evaluated . in a retrospective study , 260 bc women and invasive ductal carcinoma were included to our study in kermanshah city , iran . they received chemotherapy , radiotherapy , or hormone therapy . a sufficient sample size was selected from any patient , and the slides were stained by hematoxylin and eosin ( h and e ) method . then 4  sections were prepared for staining with h and e and also for immunohistochemical ( ihc ) ( ki-67 , er , pr , p53 , and her2 ) staining . er and pr positivity was defined as 10% positive tumor cells with nuclear staining . the her2 positive was defined as either her2 gene amplification by fluorescent in situ hybridization ( fish ) or scored as 3 + by ihc . in case of her2 ( 2 the age , tumor size , lymph node involvement , histological grade , nuclear grade , and vascular invasion were other factors that determined in a lot of patients . in this study , hormone receptor ( hr)-positive and her2-negative tumors were classified as luminal a type ; hr - positive and her2-positive tumors ( her2 ihc : 3 + or 2 + that amplifiedbyfish ) as luminal b type ; hr - negative and her2-positive tumors as her2 disease ; and hr - negative and her2-negative tumors as triple negative ( tn ) type . chicago , il , usa ) . chi - square test was used to analyze the significance of correlation between the expression of ki-67 and other parameters . in a retrospective study , 260 bc women and invasive ductal carcinoma were included to our study in kermanshah city , iran . they received chemotherapy , radiotherapy , or hormone therapy . a sufficient sample size was selected from any patient , and the slides were stained by hematoxylin and eosin ( h and e ) method . then 4  sections were prepared for staining with h and e and also for immunohistochemical ( ihc ) ( ki-67 , er , pr , p53 , and her2 ) staining . er and pr positivity was defined as 10% positive tumor cells with nuclear staining . the her2 positive was defined as either her2 gene amplification by fluorescent in situ hybridization ( fish ) or scored as 3 + by ihc . in case of her2 ( 2 the age , tumor size , lymph node involvement , histological grade , nuclear grade , and vascular invasion were other factors that determined in a lot of patients . in this study , hormone receptor ( hr)-positive and her2-negative tumors were classified as luminal a type ; hr - positive and her2-positive tumors ( her2 ihc : 3 + or 2 + that amplifiedbyfish ) as luminal b type ; hr - negative and her2-positive tumors as her2 disease ; and hr - negative and her2-negative tumors as triple negative ( tn ) type . statistical analyses were performed using the ibm spss version 19 ( spss inc . , chicago , il , usa ) . chi - square test was used to analyze the significance of correlation between the expression of ki-67 and other parameters . the mean age at diagnosis was 47.6 years ( range , 24 - 84 years ) with 100% female . of 243 patients that tumor size was determined for them , 207 patients ( 85.2% ) had tumor size 2 cm , and 36 patients ( 14.8% ) had size < 2 cm and also of 237 patients , 47 patients ( 19.8% ) , 140 ( 59.1% ) , and 50 ( 21.1% ) had histological grades i , ii , and iii , respectively [ table 1 ] . we had nuclear grade for 152 patients that 35 patients ( 23% ) , 90 ( 59.2% ) , and 27 ( 17.8% ) were grades i , ii , and iii , respectively . of 242 patients , 155 patients ( 64% ) had lymph node involvement and of 206 patients , 135 patients ( 65.5% ) had vascular invasion . of all patients , 156 ( 60% ) , 149 ( 57.3% ) , and 106 ( 40.8% ) were er , pr , and her2 positive , respectively . we divided ki-67 to two groups : 144 patients ( 55.4% ) had low ki-67 ( ki-67 < 20% ) and 116 patients ( 44.6% ) with high ki-67 ( ki-67 20% ) . the baseline characteristics of patients with breast cancer ( n = 260 ) the correlation between ki-67 with other factors in bc patients has been shown in table 2 . there is a significant correlation between ki-67 with nuclear grade , her2 , and p53 ( p < 0.05 ) . based on this result , more patients with ki-67 20% have a higher nuclear grade , p53-positive , and her2-positive . the correlation between ki67 with other factors in breast cancer patients the figure 1 shows the number of patients based on ki-67 for types of tumor . therefore , more tn patients have high ki-67 and more patients with other subtypes have low ki-67 . invasive breast carcinoma is the most common malignant tumor in women worldwide and is a heterogeneous disease with distinct pathological and histological features and can be classified into several subtypes based on the expression of 3 receptors : er , pr , and her2 . ki-67 is an immunohistochemical proliferation marker in many types of cancer and has been widely studied among bc patients mostly through retrospective studies . in our study , a number of other studies also showed that a higher ki-67 index significantly correlated with her2-positive , but in other study , her2-negative had significantly higher ki-67 values . a higher nuclear grade had a direct significantly correlation with higher ki-67 and also the overexpression of p53 bears a direct statistically significant relationship to ki-67 . in tn patients has been shown that there is a direct correlation between ki-67 and p53 that more patients with p53-positive had high ki-67 . in our study , a number of studies reported that a higher ki-67 index significantly correlated with larger tumors , positive lymph nodes . therefore , ki-67 expression in axillary lymph nodes is significantly higher in lymph nodes than that in primary cancer in some cases . a total of 194 cases of diagnosed bc were included in a study that significant association was found between ki-67 and tumor grade , pr , and lymph node status , but no link was apparent with er positivity and tumor size . a number of studies reported that among classical histopathological parameters , grading was strongly correlated to ki-67-labeling indices . other studies showed that er status has been largely identified as being inversely correlated with ki-67 , with the higher rates of er positivity shown in the lowest proliferating tumors . in our study , there is a significant correlation between tumor size , lymph node involvement , histological grade , er , and pr status with ki-67 . a study reported that in univariate analyses , high ki-67-labeling index was associated with vascular invasion . furthermore , in other studies had been shown that vascular and lymphatic invasion associated with higher ki-67 values . a higher ki-67 index significantly correlated with younger age . in a study reported that in bc , there is a strong correlation has been found between the percentage of cells positive for ki-67 and age . in our study , there was no significant correlation between ki-67 with age and vascular invasion . possible cause of the difference in the results of various studies returns to type of division for ki-67 . in a number of studies , ki-67 has been divided based on 10% and < 10% and other studies based on 20% and < 20% such as our study , and even a few studies based on other numbers . for a good result about correlation between ki-67 with other factors in bc , it needs that the researchers do the studies based on a constant and accurate number . the results in a study with 960 patients with bc showed that in luminal a patients , only one had a ki-67 level higher than 20% . in luminal b , the ki-67 was higher than 20% in 51.16% of the patients . in the her2 subtype , the data indicated that the level of ki-67 may be considered one of the valuable biomarkers in bc patients . in our study , the ki-67 20% was 45.9% , 39% , 20.8% , and 58.2% in luminal a , luminal b , her2 disease , and tn patients , respectively . therefore , tn patients have more ki-67 20% ( high ki-67 ) compared to other subtypes . the higher ki-67 has a direct significant correlation with higher nuclear grade ; p53-positive and her2-positive . furthermore , tn patients have higher ki-67 compared to other subtypes . for a good result about correlation between ki-67 with other factors in bc , it needs that ki-67 indexing divided based on a constant and accurate percent in the future studies .
context : despite the fact that breast cancer ( bc ) is a major health issue , very few studies describe its characteristics in the middle east.aim:the aim of this study was to evaluate the use and value of ki-67 as a prognostic marker in bc and associations between ki-67 , clinical , and histopathological parameters were evaluated.subjects and methods : in a retrospective study , 260 bc women and invasive ductal carcinoma were included to our study in kermanshah city , iran . 
 age , tumor size , lymph node involvement , histological grade , nuclear grade , and vascular invasion were other factors that determined in a lot of patients.results:the mean age at diagnosis was 47.6 years ( range , 24 - 84 years ) with 100% female . 
 of 243 patients that tumor size was determined for them , 207 patients ( 85.2% ) had tumor size 2 cm , and 36 patients ( 14.8% ) had size < 2 cm and also of 237 patients , 47 patients ( 19.8% ) , 140 ( 59.1% ) , and 50 ( 21.1% ) had histological grades i , ii , and iii , respectively . 
 there is significant correlation between ki-67 with nuclear grade , human epidermal growth factor receptor 2 ( her2 ) , and p53 ( p < 0.05 ) . 
 based on this result , more patients with ki-67 20% have higher nuclear grade , p53-positive , and her2-positive . 
 there was correlation between ki-67 with type of tumor ( p = 0.009).conclusions : the higher ki-67 has a direct significant correlation with higher nuclear grade , p53-positive , and her2-positive . 
 furthermore , triple negative patients have higher ki-67 compared to other subtypes .