不同分子亚型乳腺癌的MR表现

目的 探讨不同分子亚型的乳腺癌磁共振（magnetic resonance,MR）表现的差异性。方法 回顾性分析经病理证实的69例乳腺癌患者的术前乳腺MR资料,通过分析MR形态学特征、早期强化率、时间信号强度曲线（time-signal intensity curve,TIC）以及表观扩散系数（apparent diffusion coefficient,ADC）值,对病变进行联合评价。结果 69例乳腺癌患者中,共有62例患者（76个病灶）呈肿块样强化病变,其中Luminal A型乳腺癌8例（11个病灶）,Luminal B型乳腺癌35例（44个病灶）,HER-2过表达型乳腺癌9例（11个病灶）,三阴性乳腺癌10例（10个病灶）。肿块样强化病变中,不同分子亚型乳腺癌的形态差异有统计学意义（χ²=17.006,P=0.002）,其中三阴性乳腺癌形态表现为圆形的比例明显大于其他三组乳腺癌（40.00% vs 10.61%,χ²=6.390,P=0.033）;不同分子亚型乳腺癌的边缘差异亦有统计学意义（χ²=25.502,P=0.001）,其中三阴性乳腺癌边缘清晰比例显著大于其他三组乳腺癌（60.00% vs 10.61%,χ²=14.942,P=0.001）;不同分子亚型乳腺癌的内部强化方式、早期强化率、TIC类型及ADC值的差异无统计学意义（P＞0.05）。。结论 不同分子亚型乳腺癌MR表现上有一定区别,可能有助于区分三阴性乳腺癌和非三阴性乳腺癌,但目前尚不能依据MR表现乳腺癌分子亚型直接预测。     

Immunohistochemical profiles of brain metastases from breast cancer

The aim of present study is to explore the immunohistochemical profiles of brain metastases from breast cancer. We retrospectively performed immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2/neu), and cytokeratin (CK) 5/6 in 29 patients with resected tumor specimens of brain metastases. Immunohistochemical staining for ER, PgR and HER2/neu was performed in 24 patients with primary tumors. The positive frequency of immunohistochemical profiles of ER, PgR, HER2/neu, and CK5/6, in the brain metastases were 13.8%, 6.9%, 37.9%, and 24.1%, respectively. The immunohistochemical profiles including ER, PgR, and HER2/neu of the primary tumor and the brain metastasis differed in seven patients (29.2%, N = 7/24). Interestingly, the biological characteristics of brain metastasis sometimes changed which were represented by immunohistochemical staining. Therefore, the changes in the biological features of breast cancer should be taken into account when developing treatment strategies, including new molecular-targeted drugs, for brain metastases.     

Comparison of frequencies and prognostic effect of molecular subtypes between young and elderly breast cancer patients

Purpose

To compare the distribution and prognostic effect of the breast cancer molecular subtypes in young and elderly breast cancer patients.

Patients and methods

Our study population (n = 822) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1996. A total of 142/822 fresh frozen tissues were available with good quality RNA and analyzed by gene expression microarray. Gene expression molecular subtypes were determined by correlation to the expression centroids of 534 “intrinsic” genes. Sections of a tissue micro array containing formalin‐fixed paraffin‐embedded tumor tissue of 714/822 patients were immunohistochemically (IHC) stained for Ki67, EGFR, CK5/6. Tumor expression of ER, PR, HER2 was previously determined. IHC molecular subtypes were defined based on expression of these markers: Luminal A: ER+ and/or PR+, HER2– and Ki67–; Luminal B: ER+ and/or PR+ and ki67+; ERBB2: ER–, PR– and HER2+; Basal‐like: ER–, PR–, HER2– and EGFR+ and/or CK5/6+; Unclassified: ER–, PR–, HER2–, EGFR– and CK5/6–. IHC molecular subtypes were validated against gene expression defined molecular subtypes. Assessment of distribution and prognostic effect of molecular subtypes was stratified to age (<65 versus ≥65 years).

Results

Validation of molecular subtypes determined by IHC against gene expression revealed a substantial agreement in classification (Cohen''s kappa coefficient 0.75). A statistically significant association (p = 0.02) was found between molecular subtypes and age, where Luminal tumors were more often found in elderly patients, while ERBB2, basal‐like and unclassified subtypes were more often found in young patients. Molecular subtypes showed a prognostic association with outcome in young patients concerning relapse‐free period (RFP) (p = 0.01) and relative survival (RS) (p < 0.001). No statistically significant prognostic effect was found for molecular subtypes in elderly patients (RFP p = 0.5; RS p = 0.1). Additional analyses showed that no molecular subtypes showed a statistically significant difference in outcome for elderly compare to young patients.

Conclusion

We have shown that molecular subtypes have a different distribution and prognostic effect in elderly compared to young breast cancer patients, emphasizing the fact that biomarkers may have different distributions and prognostic effects and therefore different implications in elderly compared to their younger counterparts. Our results support the premise that breast cancer clinical behavior is significantly affected by patient age. We suggest that competing risks of death in elderly patients, ER‐driven differences and micro‐environmental changes in biology are underlying these age‐dependent variations in patient prognosis.     

Breast cancer subtypes identified by the ER, PR and HER-2 status in Thai women

Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2+), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, χ2). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, χ2). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, χ2). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.     

乳腺癌亚型对放疗反应及潜在放疗敏感性的影响

放射治疗（ RT）对于乳腺癌至关重要,有超过50％的患者在治疗疾病的过程中接受RT,相当于全世界每年有500000名患者接受RT,不幸的是,并不是所有的病人均能获益,部分乳腺癌患者出现了局部复发及远处转移,因此个体化放射治疗将会是一个新局面,对于放疗不敏感的肿瘤给予更高的治疗剂量,而对于放疗无效的疾病避免了不必要的损伤,更具选择性的治疗将节约卫生服务资源,减轻放射治疗机器的负担,降低癌症治疗的经济成本,但目前还没有完善的预测放射治疗的生物标志物,本文将回顾性分析探讨乳腺癌分子亚型是否可以成功预测放射治疗的有效性。     

SUCI02选择性抑制HER-2/neu受体酪氨酸激酶磷酸化及其对HER-2/neu过表达乳腺癌细胞生长的影响

背景与目的：HER-2／neu受体过度表达与肿瘤的发生发展、对化疗的敏感性以及患者预后有关;我们通过大量筛选,发现SUCI02[N-(4-乙氧苯基)-2-羟基酸胺]能抑制HER2／neu受体酪氨酸激酶磷酸化。本研究拟探讨SUCI02对HER-2／nell过度表达的肿瘤细胞生长的影响。方法：用免疫沉淀、免疫印迹法检测：HER-2／neu受体酪氨酸激酶磷酸化、酪氨酸激酶蛋白水平的变化;MTT法检测SUCI02对乳腺癌细胞的抑制作用。结果：SUCI02能抑制HER-2／neu受体的自身磷酸化,在乳腺癌MDA—MB．453m1细胞中,SUCI02对HER-2／neu受体自身磷酸化的IC50为4．34μg／ml,对HER-2／neu的表达没有任何影响。在用SUCI02处理MDA-MB-453ml细胞30min后,用培养液洗掉药物,继续培养不同时间,结果可见洗掉药物后30min,SUCI02对HER-2／neu受体磷酸化的抑制就开始恢复。SUCI02处理MDA-MB-453ml细胞后其下游靶分子MAPK和AKT激活明显受抑制,呈现剂量依赖性。SUCI02对EGFR受体酪氨酸磷酸化在最高剂量用到40μg／ml下没有明显的抑制作用。应用MTT法检测了SUCI02对过度表达HER-2／neu的MDA-MB-453ml细胞的生长抑制作用,同时应用过表达EGFR的乳腺癌MDA—MB-468细胞作为对照,结果可见SUCI02对HER-2／neu过表达的肿瘤细胞相对于过表达EGFR的肿瘤细胞有更明显的抑制作用。结论：SUCI02选择性抑制HER-2／neu受体酪氨酸激酶磷酸化,阻断其下游信号途径,对过度表达HER-2／neu的肿瘤细胞具有更强的生长抑制作用。     

Immunohistochemical and molecular analyses of HER2 status in breast cancers are highly concordant and complementary approaches

Background:

Immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) are currently the most commonly used methods to assess HER2 status. PCR-based assays allow quantitative determination of HER2 amplification (Q-PCR) or overexpression (Q-RT–PCR), but are not routinely used. We evaluated the relevance of Q-RT–PCR for HER2 status determination.

Methods:

We compared IHC and Q-RT–PCR in 466 breast tumours. In discordant or equivocal cases, five additional methods (IHC with two other antibodies, FISH, silver in situ hybridisation (SISH) and Q-PCR) were combined to determine HER2 status. Two cases with HER2 intra-tumour heterogeneity were further explored by allelic profiles analysis and HUMARA clonality determination after microdissection.

Results:

We observed 97.3% concordance between Q-RT–PCR and non-equivocal IHC. Twelve out of 466 cases (3%) revealed discordances between the two methods. The power of Q-RT–PCR to predict HER2 status (defined by seven methods) was similar to that of IHC. Although rare, some discordances between techniques might be due to HER2 intra-tumour heterogeneity and we report two examples, one tumour containing two distinct clones, another tumour consisting of HER2 amplified and non-amplified subclones.

Conclusion:

Q-RT–PCR and IHC are highly concordant methods for HER2 status assessment, and Q-RT–PCR allows a highly reliable quantitative assessment and could be a useful adjunct to IHC.     

New drugs for breast cancer subtypes: Targeting driver pathways to overcome resistance

Breast cancer is not a single disease. Genetic array tools can define several subtypes. Specific biological processes and distinct gene pathways are associated with prognosis and sensitivity to chemotherapy and targeted agents in different subtypes of breast cancers. As a consequence, breast cancer can be classified by molecular events. A primary challenge for future drug development in breast cancer will be to distinguish genes and pathways that “drive” cancer proliferation (drivers) from genes and pathways that have no role in the development of cancer (passengers). The identification of functional pathways that are enriched for mutated genes will select sub-population of patients the will most likely be sensitive to biology driven targeted agents. The selection of driver pathways in resistant tumors will permit to discover a biology-driven platform for new drug development to overcome resistance. Any of the breast cancer subtypes implies that clinicians should consider cases within the various distinct sub-population in order to properly choose the most personalized therapeutic approach. We will review all new emerging agents targeting the driver pathways within breast cancer molecular subtypes.     

Prognostic value of breast cancer subtypes on breast cancer specific survival, distant metastases and local relapse rates in conservatively managed early stage breast cancer: A retrospective clinical study

Aim

To ascertain if breast cancer subtypes had prognostic effect on breast cancer specific survival, distant metastases and local relapse rates in women affected by early stage breast cancer.

Patients and methods

Data of 774 patients affected by early stage breast cancer and treated with breast-conserving therapy were reviewed. Patients were grouped, based on steroid receptor status and HER2 status as: Luminal A (ER+/PR+/HER2−), Luminal B (ER+/PR+/HER2+), Basal-like (ER−/PR−/HER2−) and HER2 (ER−/PR−/HER2+). Distribution of variables among subtypes was evaluated with Pearson’s test. Survival rates were calculated with life tables; Cox regression stepwise method was used to identify predictive variables of survival.

Results

Median age was 55.0 years old (range 27–80) and median follow up time of 59.0 months (range 13.6–109.7). Breast cancer specific survival and distant metastases rates were different among breast cancer subtypes (both outcomes P = 0.00001) but there was no difference regarding local relapse rates (P = 0.07). Axillary nodes status (P = 0.00001), adjuvant therapy (P = 0.03) and breast cancer subtypes (P = 0.03) resulted prognostic factors of breast cancer specific survival; axillary node status (P = 0.00001) and breast cancer subtypes (P = 0.00001) had an impact on distant metastases. Age (P = 0.003), tumor size (P = 0.0001), positive or close surgical margin (P = 0.00001) and tumor grade 3 (P = 0.049) resulted prognostic factors of local relapse.

Conclusions

In our study, breast cancer subtype seems a prognostic factor of breast cancer specific survival and distant metastases rates, but not of local relapse rate. Patients could be submitted to conservative surgery, if feasible, but considering the differences in survivals, patients with worse prognosis should receive more aggressive adjuvant treatments.     

Mammographic density and molecular subtypes of breast cancer

Background:

Gene expression profiling has led to a subclassification of breast cancers independent of established clinical parameters, such as the Sorlie–Perou subtypes. Mammographic density (MD) is one of the strongest risk factors for breast cancer, but it is unknown if MD is associated with molecular subtypes of this carcinoma.

Methods:

We investigated whether MD was associated with breast cancer subtypes in 110 women with breast cancer, operated in Stockholm, Sweden, during 1994 to 1996. Subtypes were defined using expression data from HGU133A+B chips. The MD of the unaffected breast was measured using the Cumulus software. We used multinomial logistic models to investigate the relationship between MD and Sorlie–Perou subtypes.

Results:

Although the distribution of molecular subtypes differed in women with high vs low MD, this was statistically non-significant (P=0.249), and further analyses revealed no association between the MD and Sorlie–Perou subtypes as a whole, nor with individual subtypes.

Conclusion:

These findings suggest that although MD is one of the strongest risk factors for breast cancer, it does not seem to be differentially associated with breast cancer molecular subtypes. However, larger studies with more comprehensive covariate information are needed to confirm these results.     

Prevalence of hormone receptors and HER2/neu in breast cancer cases in Jordan

The management and prognosis of breast cancer nowadays require the evaluation of Estrogen (ER), Progesterone Receptors (PR) and HER2/neu. Ethnic variation in the expression of these receptors is well documented. The aim of this study is to determine the prevalence of ER, PR and HER2/neu among Jordanian women with breast cancer of ductal and lobular types. A retrospective analysis was performed on 267 cases of breast cancer referred for treatment at King Hussein Cancer Center, Jordan between the period of June 2003 and June 2004. Standard immune stains were used for evaluation of hormone receptors and HER2/neu. In addition, evaluation of HER2/neu was done by FISH in selected cases. Of these 267 cases, 240 (89.9%) were ductal carcinomas of various histological grades, 122 (50.8%) of which were ER-positive, 138 (57.5%) PRpositive and 42 (17.5%) HER2/neu-positive. Twentytwo (8.2%) of all cases were lobular carcinomas, 15 (68%) of which were ER-positive, 20 (90.9%) PRpositive and 3 (13.6%) HER2/neu-positive. Five (1.9%) of the total cases were of mixed lobular and ductal types, 4 (80%) of which were ER-positive, 3 (60%) PR-positive and none were positive for HER2/neu. The prevalence of hormone receptor positivity in breast cancer of Jordanian women is lower than that of the western populations and close to other populations such as the Chinese and the minor ethnic groups of Northern America (African Americans).     

Presence of bone marrow micrometastasis is associated with different recurrence risk within molecular subtypes of breast cancer

Expression profiles of primary breast tumors were investigated in relation to disseminated tumor cells (DTCs) in bone marrow (BM) in order to increase our understanding of the dissemination process. Tumors were classified into five pre‐defined molecular subtypes, and presence of DTC identified (at median 85 months follow‐up) a subgroup of luminal A patients with particular poor outcome (p=0.008). This was not apparent for other tumor subtypes. Gene expression profiles associated with DTC and with systemic relapse for luminal A patients were identified. This study suggests that DTC in BM differentially distinguishes clinical outcome in patients with luminal A type tumors and that DTC‐associated gene expression analysis may identify genes of potential importance in tumor dissemination.     

乳腺癌各分子亚型中骨桥蛋白的表达及其临床意义

目的： 研究骨桥蛋白（osteopontin,OPN）在乳腺癌各分子亚型中的表达及其临床意义。 方法： 收集2000年1月至2003年12 月第二军医大学长海医院的99例乳腺癌组织标本,免疫组织化学法检测ER（estrogen receptor）、PR(progesterone receptor)和HER-2（human epidermal growth factor receptor-2）的表达,并据此将乳腺癌患者分为luminal A型、luminal B型、HER-2过表达型和基底细胞样型。免疫组织化学法测定各分子亚型乳腺癌组织中OPN的表达情况,并分析OPN表达与乳腺癌患者临床病理特征的关系。 结果： 根据ER、PR和HER-2的不同表达情况,99例乳腺癌患者中luminal A型45例、luminal B型27例、HER-2过表达型14例、基底细胞样型13例。OPN在luminal A型、luminal B型、HER-2过表达型和基底细胞样型中表达率分别为22.2%、29.6%、71.4%和61.5%,HER-2过表达型和基底细胞样型乳腺癌组织中OPN表达率均高于luminal A型和luminal B型（P<0.01）。OPN低表达的乳腺癌患者生存率高于OPN高表达者,两者差异有统计学意义（P<0.01）。 结论： OPN在基底细胞样型和HER-2过表达型乳腺癌组织中高表达,其表达可作为乳腺癌预后的评估指标之一。     

乳腺浸润性导管癌超声图像特征与分子亚型的关系

背景与目的：乳腺浸润性导管癌(breast invasive ductal carcinoma,IDC)属于乳腺癌中最常见的一种类型,其各分子亚型的超声图像特征具有重要的临床价值。该研究探讨了IDC超声图像特征与其分子亚型的关系。方法：该研究回顾性分析112例具有完整术前超声图像特征及术后病理结果的IDC病例资料。其中以雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、人表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)及细胞核增值抗原(Ki-67)的免疫组织化学检测结果进行分子分型,即Luminal A型、Luminal B型、ERBB2阳性型和Basal-like型。结果：在112例IDC病例中,Luminal A型14例,占12.5%;Lu-minal B型62例,占55.4%;ERBB2阳性型21例,占18.7%;Basal-like型15例,占13.4%。4个亚型的超声图像特征在肿块长径、淋巴结数量、边界、形态和血流方面差异均有统计学意义(P<0.05);而在内部回声、微钙化、后方回声衰减及弹性成像方面差异无统计学意义(P>0.05)。在所统计的IDC病例中,Luminal A型和Luminal B型转移淋巴结数量相对少,边界多不清,形态不规则;ERBB2阳性型血供丰富,肿块较大,转移淋巴结较多;Basal-like型多边界清,形态规则,肿块大,转移淋巴结多。结论：IDC超声图像特征与其分子亚型存在一定相关性,为IDC的早期诊断、术前、术中及预后评估有重要的临床指导意义。     

Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

Introduction: Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, whichcan be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO donot recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We thereforeaimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymphnode metastasis, ER, PR and HER2neu status. Methods: A total of 194 cases of newly diagnosed breast cancerwere included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed bythe DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated bothas continuous and categorical variables. Results: Mean age of the patients was 51.7 years (24-90). Mean Ki67index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%)and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade,PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size.There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen withHER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as comparedto intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. Conclusion: Ourstudy indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognosticmarkers because we found that tumors with Ki67 higher than 30% have better prognostic profile comparedto tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis andHER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate andlow groups when considering adjuvant chemotherapy and prognostic stratification.     

P-钙粘蛋白在乳腺癌组织中的表达及临床意义

目的 探讨乳腺癌组织中P-钙粘蛋白（P-cadherin）的表达及其与临床病理特征的关系。方法 采用免疫组化SP法检测106例乳腺癌组织及30例癌旁组织中P-cadherin的表达,分析其表达与乳腺癌患者的年龄、肿瘤大小、组织学分级、TNM分期、淋巴结转移、HER-2、ER和PR的关系。结果 乳腺癌和癌旁组织中P-cadherin的阳性表达率分别为42.5％（45/106）和13.3％（4/30）,差异有统计学意义（P＜0.05）;P-cadherin表达与乳腺癌TNM分期、组织学分级、淋巴结转移、HER-2、ER和PR有关（P＜0.05）,而与年龄及肿瘤大小无关（P＞0.05）。结论 P-cadherin在乳腺癌组织中高表达,并可能与乳腺癌的恶性程度及不良预后有关。     

Immunohistochemical Analysis of ER,PR, Her2 and CK5/6 in Infiltrative Breast Carcinomas in Indian Patients

Aim: Breast cancer is biologically a heterogeneous disease. Patients with the same diagnostic profile havemarkedly different clinical outcomes. Gene expression studies identified distinct breast cancer subtypes thatdiffer in prognosis. Aim is to identify the immunohistochemical subtypes of breast carcinoma and correlate theresults with pathological features associated with adverse prognosis in our study population. Method: We included107 consecutive cases of invasive breast carcinoma and sub classified using immunohistochemical staining forER, PR, Her2, and CK5/6 into the following subtypes: luminal A, luminal B, basal-like, Her2+ and unclassified.Associations between tumor subtypes and tumor characteristics were examined. Results: The proportion ofeach subtype in our patient population was: luminal A 37.4%, luminal B 11.1%, Her2+ 29% and basal-like7.5%. The following variables were significantly associated with IHC breast cancer subtypes: patient age (p<.05),overall histopathology grade (p<0.001), nuclear grade (p<0.005) and mitotic index (p<0.001). Her2+ and basallike subtypes were associated with poor differentiation (p<0.01), higher nuclear grade (p<0.05) and high mitoticindex (p<0.05). Conclusions: Our data show a higher proportion of patients in the study population undergototal mastectomy and harbor poorly differentiated, node positive tumors than reported. There was also a relativelyhigh percentage of the Her2+ subtype (29%).     

Immunohistochemical Evaluation of Ki-67 and Comparison with Clinicopathologic Factors in Breast Carcinomas

Background: Patients primarily received tamoxifen based on their menopausal status due to the lack ofimmunohistochemistry. A recent study has shown that hormonal receptors were not correlated with menopausal status,and thus, indicating that they present limited therapeutic and prognostic significance in breast cancer management.This study aimed to evaluate Ki-67 value and analyze its association with clinicopathologic parameters in breast cancerpatients. Methods: The formalin-fixed paraffin-embedded breast tissue blocks of 125 patients with primary breastcarcinomas were subjected to immunohistochemical analysis using Ventana Benchmark® GX automated immunostainer.Analysis of variance and Chi-2 test were used to examine the relationship between Ki-67 and clinicopathologicvariables. Results: The mean age of 125 patients included in the study was 47.7 years. The average score of Ki-67was 56.0%. 84.8% of patients showed Ki-67 ≥ 14%. Mean scores of Ki-67 were correlated with grade (p = 0.006),PR (p = 0.026), histological type, ER, combined ER/RP, and molecular subtype (p < 0.001). Ki-67 was independentof HER2 (p = 0.402) and menopausal status (p = 0.471). The frequency of Ki-67 according to St Gallen 2011 wasassociated with histological type (p = 0.005), grade (p = 0.005), ER (p < 0.001), combined ER/PR (p = 0.004), andmolecular subtype (p = 0.004). There was no significant relationship between the distribution of Ki-67 and the age ofthe patients (p = 0.859), menopausal status (p = 0.979), PR (p = 0.149), and HER2 (p = 0.597). Conclusion: Ki-67 isuseful for treatment decisions in primary breast cancer patients. The high value of Ki-67 was associated with adverseclinicopathologic factors. The increased Ki-67 value should be carefully investigated in triple negative patients.