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

Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may helpto identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determinedby Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: Weobtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes weredefined 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 ofHG; 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 betweenKi67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patientswere treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information tobe included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). Weperformed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before andafter chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), bothcategorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patientshad pathologic complete response (cPR). Conclusions: In our experience we did not find associations betweenKi67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.     

Tumor Mutation Burden Prediction Model in Egyptian Breast Cancer patients based on Next Generation Sequencing

Objectives: This study aimed to identify the tumor mutation burden (TMB) value in Egyptian breast cancer (BC) patients. Moreover, to find the best TMB prediction model based on the expression of estrogen (ER), progesterone (PR), human epidermal growth factor receptor 2 (HER-2), and proliferation index Ki-67. Methods: The Ion AmpliSeq Comprehensive Cancer Panel was used to determine TMB value of 58 Egyptian BC tumor tissues. Different machine learning models were used to select the optimal classification model for prediction of TMB level according to patient’s receptor status. Results: The measured TMB value was between 0 and 8.12/Mb. Positive expression of ER and PR was significantly associated with TMB ≤ 1.25 [(OR =0.35, 95% CI: 0.04–2.98), (OR = 0.17, 95% CI= 0.02-0.44)] respectively. Ki-67 expression positive was significantly associated with TMB >1.25 than those who were Ki-67 expression negative (OR = 9.33, 95% CI= 2.07-42.18). However, no significant differences were observed between HER2 positive and HER2 negative groups. The optimized logistic regression model was TMB = -27.5 -1.82 ER – 0.73 PR + 0.826 HER2 + 2.08 Ki-67. Conclusion: Our findings revealed that TMB value can be predicted based on the expression level of ER, PR, HER-2, and Ki-67.     

Expression of p53 Breast Cancer in Kurdish Women in the West of Iran: a Reverse Correlation with Lymph Node Metastasis

Background: In breast cancer (BC), it has been suggested that nuclear overexpression of p53 protein might be an indicator of poor prognosis. The aim of the current study was to evaluate the expression of p53 BC in Kurdish women from the West of Iran and its correlation with other clinicopathology figures. Materials and Methods: In the present retrospective study, 231 patients were investigated for estrogen receptor (ER) and progesterone receptor (PR) positivity, defined as 10% positive tumor cells with nuclear staining. A binary logistic regression model was selected using Akaike Information Criteria (AIC) in stepwise selection for determination of important factors. Results: ER, PR, the human epidermal growth factor receptor 2 (HER2) and p53 were positive in 58.4%, 55.4%, 59.7% and 45% of cases, respectively. Ki67 index was divided into two groups: 54.5% had Ki67<20% and 45.5% had Ki67 20%. Of 214 patients, 137(64%) had lymph node metastasis and of 186 patients, 122(65.6%) had vascular invasion. Binary logistic regression analysis showed that there was inverse significant correlation between lymph node metastasis (P=0.008, OR 0.120 and 95%CI 0.025-0.574), ER status (P=0.006, OR 0.080, 95%CI 0.014-0.477) and a direct correlation between HER2 (P=005, OR 3.047, 95%CI 1.407-6.599) with the expression of p53. Conclusions: As in a number of studies, expression of p53 had a inverse correlation with lymph node metastasis and ER status and also a direct correlation with HER2 status. Also, p53-positivity is more likely in triple negative BC compared to other subtypes.     

乳腺癌临床病理指标以及分子分型对TEC新辅助化疗病理完全缓解的预测价值

目的  本研究旨在探讨乳腺癌临床病理指标以及乳腺癌分子分型对多西他赛联合表柔比星、环磷酰胺（TEC）的 新辅助化疗后病理完全缓解率（pathological complete response pCR）的预测价值。方法   对 214例经4周期TEC新辅助化疗的乳腺癌患者的临床病理资料进行回顾性分析;免疫组织化学检测经核心针穿刺 的癌组织雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体-2（HER2）、Ki67、p53表达情况,原位基 因免疫荧光杂交（FISH）检测HER2有无过表达;根据ER、PR、HER2、Ki67的表达情况将乳腺癌分为4种分子分型： LuminalA、 LuminalB、HER2过表达型和三阴性乳腺癌。分析不同的临床病理指标、不同分子分型与pCR的相关性。结果  4周期TEC新辅助化疗后pCR率为14.0%（30/214）;单因素分析：ER、PR、Ki67、乳腺癌分子分型与pCR均具有显 著相关性（P＜0.05）;乳腺癌分子分型各组间显示pCR率不同：LuminalA＜LuminalB＜HER2过表达型＜三阴性乳腺癌 ;多因素分析：与pCR具有显著相关性的分类变量为ER（OR=0.311,95%CI：0.136～0.712;P=0.006）和Ki67 （OR=2.788,95%CI：1.061～7.327;P=0.038）。结论  ER、PR、Ki67以及乳腺癌分子分型可能是TEC新辅助化疗后乳腺癌pCR的预测指标。     

Do estrogen,progesterone, P53 and Ki67 receptor ratios determined from curettage materials in endometrioid-type endometrial carcinoma predict lymph node metastasis?

Aim: Estrogen receptor (ER), progesterone receptor (PR), and Ki-67 and P53 receptor levels in endometrial curettage material were investigated for their ability to predict lymph node (LN) involvement in patients with endometrioid-type endometrial cancer (EEC).Methods: This retrospective study was based on a review of the records of patients who were diagnosed with EEC and underwent both hysterectomy and systematic retroperitoneal lymphadenectomy at the Gynecologic Oncology Clinic of Tepecik Training and Research Hospital, Turkey, between January 2008 and August 2017.Results: The curettage materials of 138 EEC patients were analyzed for ER, PR and P53 and Ki-67 receptor levels. According to the pathology results, the median pelvic LN count was 20 (range: 12-49) and the para-aortic LN count was 14 (10-46). Retroperitoneal LN involvement was present in 18 patients (13.0%). The association of LN involvement with all receptors was significant. The combined ratio of the 2 groups of markers ([P53 + Ki67]/[ER + PR]) (≥0.71) was an independent risk factor for LN involvement. In addition, in a univariate logistic regression analysis all receptors were significant predictors of LN involvement.Conclusions: In the detection of LN involvement, determination of the receptor status in curettage material has a high sensitivity and specificity. In EEC patients, receptor levels in curettage materials can be evaluated to detect LN involvement preoperatively.     

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.     

Higher rate of progesterone receptor positivity in skeletal metastases of breast cancer with a pathological fracture vs those without fracture

Identifying risk factors for fracture occurrence in breast cancer (BC) skeletal metastases (SM) may guide the management of such bone deposits. There is sparse evidence regarding receptor status in SM and their relationship to fracture occurrence. Our study aimed to determine the relationship between estrogen (ER), progesterone (PR) and HER2 receptor status and Ki-67 index and fracture occurrence in SM of BC. Exactly 152 samples of SM of BC obtained from individual patients were evaluated. The status of the aforementioned receptors and Ki67 index were determined in SMs samples. Their expression was compared between SM that did and did not develop a fracture. Ninety-one cases sustained a pathological fracture at the SM site, and 61 did not. Patients who sustained a pathological fracture had a higher rate of PR positivity at their SMs as compared to those with no fracture. There was no significant difference between the two groups concerning ER, HER2+ or Ki67 status. SMs secondary to BC with a fracture are more likely to be PR positive than those with no fracture. Determining the receptor status in SMs may identify high-risk groups for fracture occurrence, and determining the PR status may also guide surgical and hormonal therapy.     

中国上海地区乳腺癌的临床病理特征分析

目的 研究上海地区乳腺癌患者的临床病理特征。方法统计2008年至2010年上海地区1122例乳腺癌患者的相关临床病理特征,并分析它们之间的联系。结果 男性乳腺癌比例为0.89％,低于其他地区。患者发病平均年龄为53岁（中位55岁）,其中51～70岁人数最多,占43.85％。就诊时绝大多数为Ⅱ期,其中49.02％患者伴有淋巴结转移。病理分型中浸润性非特殊癌占94.47％,其中浸润性导管癌为90.91％,与国内其他地区相比,特殊类型癌比较少,占3.57％。中位肿瘤直径为3cm,巨大型肿瘤较少。三阴性乳腺癌占1881％,ER、PR、HER-2的阳性表达率分别为48.6％、59.4％和23.5％。术后病理分期与ER表达呈负相关,与HER-2呈正相关,与PR、Ki-67、E-cadherin、p53、TOPO-Ⅱ、p27、CK5／6均无关。组织学分级可能与E-cadherin有关（P=0.051）,与其他表达无关。淋巴结转移与HER-2表达呈正相关;肿瘤大小与ER表达呈负相关,与HER-2表达呈正相关。ER表达与PR呈正相关,与HER-2、Ki-67及p53呈负相关。HER-2与ER、PR、CK5／6表达呈负相关,与Ki-67、TOPO-Ⅱ呈正相关。Ki-67与TOPO-Ⅱ、HER-2表达呈正相关,与ER、p53、p27呈负相关。结论 上海地区乳腺癌患者的临床病理特征具有地域性,联合检测ER、PR、HER-2、Ki-67和p53对其诊断并指导治疗具有一定的临床意义。     

Breast cancer subtype approximations and loco-regional recurrence after immediate breast reconstruction

Background

A small but significant proportion of patients with breast cancer (BC) will develop loco-regional recurrence (LRR) after immediate breast reconstruction (IBR). The LRR also varies according to breast cancer subtypes and clinicopathological features.

Methods

We studied 1742 consecutive BC patients with IBR between 1997 and 2006. According to St Gallen conference consensus 2011, its BC approximations were applied to classify BC into five subtypes: estrogen receptor (ER) and/or progesterone receptor (PgR) positive, HER2 negative, and low Ki67 (<14%) [luminal A]; ER and/or PgR positive, HER2 negative and high Ki67(≥14%) [luminal B/HER2 negative]; ER and/or PgR positive, any Ki67 and HER2 positive [luminal B/HER2 positive]; ER negative, PgR negative and HER2 positive [HER2 positive/nonluminal]; and ER negative, PgR negative and HER2 negative [triple negative]. Cumulative incidences of LRR were compared across different subgroups by means of the Gray test. Multivariable Cox regression models were applied.

Results

Median follow up time was 74 months (range 3–165). The cumulative incidence of LRR was 5.5% (121 events). The 5-year cumulative incidence of LRR was 2.5% for luminal A; 5.0% for luminal B/HER2 negative; 9.8% for luminal B/HER2 positive; 3.8% for HER2 non luminal; and 10.9% for triple negative. On multivariable analysis, tumor size (pT) >2 cm, body mass index (BMI) ≥25, triple negative and luminal B/HER2 positive subtypes were associated with increased risk of LRR.

Conclusion

Luminal B/HER2 positive, triple negative subtypes and BMI ≥25 are independent prognostic factors for risk of LRR after IBR.     

Association of Histopathological Markers with Clinico- Pathological Factors in Mexican Women with Breast Cancer

Background: Breast cancer (BCa) is the most common malignancy in Mexican women. A set of histopathological markers has been established to guide BCa diagnosis, prognosis and treatment. Nevertheless, in only a few Mexican health services, such as that of the Secretariat of National Defense (SEDENA for its acronym in Spanish), are these markers commonly employed for assessing BCa. The aim of this study was to explore the association of Ki67, TP53, HER2/neu, estrogenic receptors (ERs) and progesterone receptors (PRs) with BCa risk factors. Materials and Methods: Clinical histories provided background patient information. Immunohistochemical (IHC) analysis was conducted on 48 tissue samples from women diagnosed with BCa and treated with radical mastectomy. The Chi square test or Fisher exact test together with the Pearson and Spearman correlation were applied. Results: On average, patients were 58±10.4 years old. It was most common to find invasive ductal carcinoma (95.8%), histological grade 3 (45.8%), with a poor Nottingham Prognostic Index (NPI; 80.4%). ERs and PRs were associated with smoking and alcohol consumption, metastasis at diagnosis and Ki67 expression (p<0.05). PR+ was also related to urea and ER+ (p<0.05). Ki67 was associated with TP53 and elevated triglycerides (p<0.05), and HER2/neu with ER+, the number of pregnancies and tumor size (p<0.05). TP53 was also associated with a poor NPI (p <0.05) and CD34 with smoking (p<0.05). The triple negative status (ER-/PR-/HER2/neu-) was related to smoking, alcohol consumption, exposure to biomass, number of pregnancies, metastasis and a poor NPI (p<0.05). Moreover, the luminal B subtype was associated with histological type (p=0.007), tumor size (p=0.03) and high cholesterol (p=0.02). Conclusions: Ki67, TP53, HER2/neu, ER and PR proved to be related to several clinical and pathological factors. Hence, it is crucial to determine this IHC profile in women at risk for BCa. Certain associations require further study to understand physiological/biochemical/molecular processes.     

局部进展期乳腺癌新辅助化疗前后生物标志物表达变化与疗效的相关性

目的：探讨局部进展期乳腺癌行新辅助化疗前后相关生物标志物的表达变化情况与化疗疗效的相关性。方法：采用免疫组化方法检测102例新辅助化疗前后局部进展期乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体－2（HER －2）、p53和增殖细胞核抗原（Ki －67）等表达,分析化疗前后生物标志物表达变化与化疗疗效的相关性。结果：ER 阴性组、PR 阴性组、Ki －67高表达组的新辅助化疗有效率分别为50．0％、49．1％、51．4％,高于 ER 阳性组26．0％、PR 阳性组25．5％、Ki －67低表达组9．4％（P ＜0．05）。Logistic 多因素回归分析显示,ER、Ki －67的表达水平是评估化疗疗效的独立因素（P ＜0．05）。Luminal 型乳腺癌总生存期高于 non －Luminal 型（Long －rank 检验,P ＜0．05）。结论：ER、Ki －67、分子亚型可作为局部进展期乳腺癌新辅助化疗疗效判断的重要预测指标。     

Roles of Ki67 in Breast Cancer - Important for Management?

Background: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer. Materials and Methods: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22. Results: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy. Conclusions: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.     

Estrogen receptor, progesterone receptor, and HER2-neu expression in first primary breast cancers and risk of second primary contralateral breast cancer

Breast cancer survivors have a 60?% higher risk of developing a second primary asynchronous contralateral breast cancer (CBC) compared to women's risk of developing a first primary breast cancer (FBC). However, little is known about how expression of tumor markers in first breast cancers influences CBC risk. We conducted a population-based nested case-control study among women 20-74?years of age diagnosed with a first breast cancer between 1996 and 2008 in western Washington State to evaluate the association between their tumor's estrogen receptor (ER), progesterone receptor (PR) and HER2-neu (HER2) expression, and risk of CBC. The study included 482 cases diagnosed with both a FBC and a CBC and 1,506 control women diagnosed only once with breast cancer identified through our local Surveillance, Epidemiology and End Results (SEER) cancer registry. Compared to the women whose FBC was ER+/PR+, those with ER-/PR- first tumors had a 1.6-fold (95?% confidence interval (CI): 1.2-2.3) increased risk of developing a CBC. When evaluated by joint ER/PR/HER2 status, compared to women with ER+/HER2- first cancers, those with HER2-overexpressing (ER-/HER2+) and triple-negative disease (ER-/PR-/HER2-) had 2.0-fold (95?% CI: 1.1-3.8) and 1.4-fold (95?% CI: 0.9-2.3) elevated risks of developing CBC, respectively. Beyond the known higher risks of mortality among patients diagnosed with more aggressive BC subtypes, here, we observe that they may also have increased risks of developing CBC.     

Biological characteristics of luminal subtypes in pre- and postmenopausal estrogen receptor-positive and HER2-negative breast cancers

Background

Estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negetive breast cancers can be divided into luminal A and luminal B subtypes based on Ki67 expression levels. However, the biological differences in ER and progesterone receptor (PR) expression levels between these luminal subtypes are not clear.

Methods

We examined immunohistochemical expression levels of ER, PR, and Ki67 in 180 ER-positive/HER2-negative breast cancers while taking menopausal status into account. Breast cancers were divided according to ER and PR levels (H: >50%, L: ≤50%), and luminal A and B were classified by the Ki67 labeling index (A: Ki67 <14%, B: Ki67 ≥14%).

Results

When breast cancers were classified based on ER and PR levels, the distribution of pre- and postmenopausals was significantly different for luminal A (P < 0.0001), but not for luminal B cancers. As for luminal A, ER-H/PR-L cancers were rare among premenopausals (8%), but frequent among postmenopausals (54%). Correlation between ER and PR levels among luminal A cancers was strong in premenopausals but weak in postmenopausals. Since crosstalk with growth factor signaling is unlikely in luminal A, we speculate that intratumoral estrogen insufficiency contributed to the characteristics of postmenopausal ER-H/PR-L cancers.

Conclusion

We speculate that the biological characteristics of luminal A cancers are influenced by the estrogen environment, but its influence on luminal B cancers may be limited. We believe these considerations constitute useful information for a better understanding of the biology of ER-positive-HER2-negetive breast cancers.     

Prognostic Value of Circulating Tumor Cells According to Immunohistochemically Defined Molecular Subtypes in Advanced Breast Cancer

BackgroundBreast cancer is a heterogeneous disease. Circulating tumor cell (CTC) enumeration might be useful to identify different risk categories within each molecular subtype.MethodsWe retrospectively analyzed 203 consecutive patients with metastatic breast cancer with baseline CTC enumeration performed with CellSearch (Veridex Corp, Warren, NJ) between March 2005 and July 2011. Patients were categorized into 3 prognostic groups based on the number of CTCs (0, 1-4, and ≥ 5) and into 5 categories based on tumor biological characteristics: luminal-A (estrogen receptor [ER] and progesterone receptor [PR] > 1%, grade 1/2, human epidermal growth factor 2 [HER2]-negative [HER2^?], Ki67 value < 14%); luminal-B (ER and/or PR > 1%, grade 3, HER2^?, Ki67 value > 14%); luminal-B HER2–positive [HER2⁺] (ER and/or PR > 1%, any grade, HER2⁺, Ki-67 value any); HER2⁺ (HER2 overexpressed/fluorescence in situ hybridization [FISH] amplified, ER and PR absent); triple negative (TN) (ER and PR 0%, HER2 not overexpressed/FISH not amplified).ResultsMedian age was 57 years (range 31-78 years). Twenty-seven patients (13.3%) had luminal-A category, 105 (51.7%) patients had luminal-B, 29 (14.3%) patients had luminal-B HER2⁺, 24 patients (11.8%) had HER2⁺, and 18 patients (8.9%) had TN. CTCs were mostly found in patients with luminal-A/luminal-B HER2^? subtype. At multivariable analysis, CTC count was a significant predictive factor for overall survival (OS) in all molecular subtypes (log-rank P < .01). Patients with 0 CTCs/7.5 mL blood and all subtypes, except HER2⁺, seem to perform better compared with other categories.ConclusionThese findings confirm CTCs as an important prognostic factor for metastatic breast cancer in all molecular subtypes. Larger studies could help identify metastatic breast cancer subgroups in which CTC analysis would be particularly useful.     

Prognostic value of hormonal receptors, p53, ki67 and HER2/neu expression in epithelial ovarian carcinoma

OBJECTIVE: The role of molecular and biological factors in ovarian cancer is controversial. We investigated the levels of the estrogen (ER) and progesterone (PR) receptors, HER2/neu, p-53 and Ki 67 in patients with advanced ovarian cancer and correlated the results with the clinical course in order to define their predictive or prognostic significance. METHODS: Paraffin-embedded tumor tissues from 72 patients with ovarian cancer treated from 1999 to 2003 were analyzed. Overexpression of C-erb-B2 was defined as herceptest ++/+++ and positive fluorescence in situ hybridization (FISH) or herceptest +++/+++. Positivity for ER and PR was determined by > or =10% of the cellular membranes immunostained. Statistical analysis was performed to evaluate the prognostic impact of the molecular markers. RESULTS: 49 of the 72 patients were ER + (68%) and 36 PR + (50%). In 45 patients (62.5%) expression of p53 was > or =10%. Overexpression of C-erb-2 was found in 4 tumor samples (5%). A Ki67 labelled nuclear area >30% was found to be associated with a higher rate of complete response (chi(2); p=0.05). None of the biological markers were significantly associated with progression free survival (PFS). By multivariate analysis residual tumor after debulking surgery and ER status were associated with OS (p< or =0.05). CONCLUSIONS: Ki67 nuclear expression >30% is predictive of complete response in advanced ovarian cancer. HER2/neu overexpression is scarce in our study. Positive ER is an independent prognostic factor for OS. Further research with larger studies and hormonal treatment is guaranteed.     

Correlations between HER2 Expression and Other Prognostic Factors in Breast Cancer: Inverse Relations with the Ki-67 Index and P53 Status

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as 10% positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3 by IHC. For HER2 (2), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor sizealso Ki-6720% as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index 20% in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-6720% had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.     

Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program

BackgroundMale breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period.MethodsPatients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States).ResultsOf 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0–23.8) for all, 7.2 years (0.0–23.2), for M0, 2.6 years (0.0–12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+ (P = 0.001), highly PR+ (P = 0.002), highly AR+ disease (P = 0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade.ConclusionsMale BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.     

p53、Ki-67、TopoⅡ、GST、P170对三阴乳腺癌预后的相关性分析

目的 探讨p53、Ki-67、DNA拓扑异构酶Ⅱ(DNA topoisomeraseII,TopoII)、谷胱甘肽转移酶(glutathione-S-transfreases,GST)、P-糖蛋白(P-glycoprotein,P170)免疫组化的表达在三阴乳腺癌发生发展中的生物学特征及其对预后评估的意义。方法 回顾性分析1993年1月-2003 年12月我院初诊乳腺癌病人共515 例进行筛选,共得出88例三阴乳腺癌(ER、PR、HER-2 均为阴性)。根据ER、PR、HER-2的表达,将其分为3组:三阴组(ER-、PR-、HER-2-)、HR组(ER+ /PR+HER-2-)和HER-2组(ER-、PR-、HER-2+)。统计这3组三阴乳腺癌标本p53、Ki-67、 TopoⅡ、GST、P170 的表达,并调查这3组病人5 年无病生存率与5 年内死亡率。结果 与非“三阴”乳腺癌相比,“三阴”乳腺癌患者p53、P170、Ki-67、GST表达水平均为最高(59.5%、78.6%、19.0%、66.7%),在术后5年内三阴组的复发率为23.9%,死亡率为22.7%,复发风险(HR 2.46,CI:1.04-5.84;P＜0.05)和死亡风险(HR 2.77,CI:1.09-7.02;P＜0.05),之后明显降低。结论 p53、P170、Ki-67、GST 在三阴乳腺癌的高表达与其不良预后具有相关性。     

Induction chemotherapy for breast carcinoma: predictive markers and relation with outcome

Induction chemotherapy provides an excellent model for evaluation of potential predictive factors. We studied expression of SBR grade, estrogen (ER) and progesterone (PR) receptors, HER2, Ki67 and P53 on core biopsies before and after chemotherapy in a series of 115 patients, who received anthracycline-based induction chemotherapy for primary breast cancer. HER2 overexpression independently predicted response to neoadjuvant anthracycline-based chemotherapy. Patients with HER2-positive status are 4.54 times more likely to have a pathological complete response than those with negative status (p<0.005). HER2, ER and PR status were stable during treatment. P53 and Ki67 significantly increased after treatment (p<0.005 and p<0.0005). SBR grade, proliferation markers, ER evaluated before and after treatment predicted disease-free survival (DFS) in univariate analysis.