Prognostic value of Ki-67 labeling index in patients with node-negative, triple-negative breast cancer

The aim of this analysis was to investigate the usefulness of Ki-67 labeling index (LI) for the identification of different prognostic subgroups in primary node-negative, triple negative breast cancer (TNBC) patients. From January 1997 to December 2005, 1,053 patients operated for TNBC were identified through the institutional clinical database. The study was performed in accordance with REMARK criteria. The relationship between Ki-67LI and the risk of breast-related deaths was evaluated with a multivariable Cox regression model. Cubic splines were used to model Ki-67LI as a continuous variable. We selected 496 consecutive patients with node-negative TNBC. Median age was 52 years, median Ki-67LI 48% (range 4-95), and median follow up 6 years (range 0.5-13). Total deaths and deaths from BC were 52 (10.5%) and 38 (7.7%), respectively. Ki-67LI increased with decreasing age (P<0.01), increasing tumor size (P<0.01), and grade (P<0.01). When analyzing Ki-67LI as a continuous variable, the risk of death from BC increased steeply with increasing Ki-67LI up to about 35% and remained flat for higher values (adjusted effect of Ki-67 P=0.049; adjusted nonlinear effect P=0.021). Accordingly, when dividing patients into lower (≤35%) and higher (>35%) Ki-67LI subgroups, the 5-year cumulative incidence of breast-related deaths were 2.3 and 9.0%, respectively, with an adjusted HR(>35 vs ≤35) of 2.3 (95% CI 1.0-5.8, P=0.046). Within the group of patients with node-negative TNBC, Ki-67LI was associated with different prognoses subgroups. Ki-67LI might be useful in the design of trials of risk-adapted adjuvant therapies.     

Biological Characteristics and Long-term Outcomes in Node-negative Breast Cancer

BackgroundBecause the risk of relapse of node-negative breast cancer (BC) is varying, we evaluated the prognosis of patients with this disease and the factors associated with increased risk of relapse.Patients and MethodsThe clinical charts of patients with BC with evidence of negative nodes and with a potential ≥ 5-year follow-up were retrospectively reviewed.ResultsWe analyzed 1276 patients. Over a median follow-up of 71.6 months (range, 1-227.2 months), we observed 159 events of relapse or death. The median RFS was 170 months. The median overall survival (OS) was 192 months. At univariate analysis, older age, negative hormonal receptors, larger tumor size and higher proliferation index (Ki67) were associated with worse recurrence-free survival (RFS) and OS (P < .05); higher grading was associated with worse RFS (P = .01). At multivariate analysis for RFS, age, Ki67 and tumor size confirmed their independent prognostic role. At multivariate analysis for OS, age and positive hormonal receptors showed an independent prognostic role. We observed no differences in prognosis between human epidermal growth factor receptor 2 (HER2) positive and triple-negative (TN) BC, but TNBC showed a worse OS compared with luminal-like BC.ConclusionsIn node-negative BC, age, hormone receptor status, tumor size and Ki67 were prognostic factors. The TNBC subtype was not associated with poorer prognosis compared with the HER2-positive subtype, but showed a worse OS compared with luminal-like BC.     

Role of Ki67 in predicting resistance to adjuvant tamoxifen in postmenopausal breast cancer patients

IntroductionBreast cancer (BC) is a major health problem in Egypt and worldwide. Its prognosis depends not only on tumor stage but also on tumor biology.AimTo correlate the expression of Ki67 with the clinical outcomes of early hormone-receptor positive postmenopausal BC patients who are receiving tamoxifen.MethodsThis cohort study included 70 patients. They were followed up for a minimum of 2 years. Ki67 was assessed on paraffin-embedded blocks using immunohistochemistry methods.ResultsThe median Ki67 value was 22.5% (IQR, 10%–50%). Ki67 was significantly higher in patients with HER2 positive tumors compared to HER2 negative tumors. After a median follow up period of 53 months, 22 patients (31%) developed disease recurrence either loco-regional or distant in 5.7% and 30%, respectively. Recurrent patients had significantly higher tumor stage, nodal stage and Ki67 values compared to non-recurrent cases. The 2-, 3- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 100% & 91%, 98% & 84% and 77% & 59%, respectively. DFS was significantly worse with higher TNM stage, lower ER expression and higher Ki67 values. OS was significantly worse in patients with Ki67 values ?30%. Ki67 ?30% was an independent predictor of recurrence, poor DFS and OS.ConclusionHigh Ki67 expression is predictive of poor prognosis and of resistance to adjuvant tamoxifen therapy in postmenopausal BC. We recommend considering Ki67 as one of the risk factors that guide adjuvant treatment decisions.     

Ki67 for evaluating the prognosis of gastrointestinal stromal tumors: A systematic review and meta-analysis

Overexpression of Ki67 is observed in tumor cells, and it has been suggested to be a marker for cancer prognosis. However, the relationship between Ki67 expression and the risk of recurrence of gastrointestinal stromal tumors (GISTs) remains poorly defined. In the present study, a meta-analysis was used to examine the associations between Ki67 levels and GIST recurrence. Studies reporting GIST and Ki67 were found by searching Cochrane Library, PubMed and Embase until October 14, 2021. The Newcastle-Ottawa Scale (NOS) was used to verify the quality of the evidence. Totally, 1682 patient cases were included. The odds ratio (OR) estimates and 95% confidence interval (CI) for each publication were determined by a fixed-effects (Mantel-Haenszel) model. A total of 20 studies that fulfilled the inclusion criteria were finally included in the analysis. The average score of quality evaluation was 6.4 points according to NOS. It was found that Ki67 levels were significantly higher in the NIH L group compared with the NIH VL group (OR: 0.51; 95% CI: 0.26-0.99; P=0.04; P heterogeneity=0.44). There was also greater Ki67 overexpression in the NIH I group compared with the NIH L group (OR: 0.45, 95% CI: 0.31-0.65; P<0.0001; P heterogeneity=0.32), while Ki67 levels were greater in the NIH H group than in the NIH I group (OR: 0.20; 95% CI: 0.15-0.28; P<0.00001; P heterogeneity=0.56). In conclusion, Ki67 overexpression may be a useful marker of the risk of recurrent GIST transformation.     

2108例T1~2期乳腺癌患者腋窝淋巴结转移的相关因素分析

目的：探讨T1~2期乳腺癌患者临床与病理因素与腋窝淋巴结转移的关系,指导前哨淋巴结活检术（SL-NB）的应用,以避免腋窝清扫术（ALND）后并发症的发生。方法收集接受手术且经病理确诊的T1~2期乳腺癌病例,对其临床病理资料进行回顾性统计分析。通过单因素分析和多因素Logistic回归分析寻找乳腺癌发生腋窝淋巴结转移的影响因素。结果共2108例患者入组,其中1021例患者发生淋巴结转移（48.4%）。单因素分析显示年龄、肿瘤大小、病理类型、组织学分级、脉管瘤栓、ER、PR、Ki-67指数以及分子分型等因素与淋巴结转移有关（P﹤0.05）;而HER-2是否过表达与淋巴结转移无关。多因素Logistic回归分析显示,患者的腋窝淋巴结转移的独立影响因素为肿瘤大小、病理类型、组织学分级、脉管瘤栓、ER表达状况（P﹤0.05）;而年龄也可能是腋窝淋巴结有无转移的独立影响因素（P=0.053）。结论肿瘤越大、分化越差、伴脉管瘤栓、ER阳性表达以及病理类型为浸润性小叶癌的T1~2期乳腺癌患者的淋巴结转移风险更高,而年龄≤50岁也可能增加了腋窝淋巴结转移的风险。T1~2期乳腺癌患者是否直接行ALND应持谨慎的态度。     

三阴性乳腺癌组织Ki-67指数预后价值分析

目的 Ki-67是细胞增殖的相关抗原,Ki-67指数是区分乳腺癌Luminal A型和Luminal B型的重要生物学指标,高Ki-67指数往往预示着不良的预后.然而在三阴性乳腺癌(triple negative breast cancer,TNBC)中,Ki-67预后价值尚不明确.本研究旨在探讨TNBC中Ki-67指数的预后价值.方法 回顾性分析郑州大学附属肿瘤医院2009-01-06-2010-12-30收治的310例经病理确诊为TNBC并有完整资料和随访数据患者的临床及病理资料,分析Ki-67指数等指标对患者生存预后影响.利用SPSS 17.0软件,计数资料比较采用χ2检验.Ki-67诊断价值及截断值采用ROC曲线进行分析.生存分析采用Kaplan-Meier法,并进行Log-rank检验.多因素分析采用Cox比例风险模型.结果 中位随访时间65个月(3~81个月),310例乳腺癌患者中复发68例(21.9%),死亡49例(15.8%),其中48例死于乳腺癌(15.5%).Ki-67指数与患者月经状态(χ2=8.484,P=0.014)、肿瘤大小(χ2=17.580,P=0.007)、腋窝淋巴结状态(χ2=30.071,P<0.001)以及组织学分级(χ2=17.626,P=0.001)均相关.低(Ki-67≤20%)、中(20%50%)5年无病生存率(disease-free survival,DFS)分别为96.5%、87.3%和64.9%,差异有统计学意义,P<0.001;5年总生存率(overall survival,OS)分别为96.5%、90.2%和75.5%,差异有统计学意义,P<0.001.Ki-67评价TNBC患者DFS及OS的ROC曲线下面积分别为0.707和0.689,Ki-67评价预后最佳截断值为57.5%.单因素分析中,Ki-67指数(χ2=31.779,P<0.001)、肿瘤大小(χ2=140.260,P<0.001)、腋窝淋巴结状态(χ2=120.467,P<0.001)和组织学分级(χ2=8.765,P=0.012)是影响TNBC患者DFS的相关因素,Ki-67指数(χ2=18.218,P<0.001)、肿瘤大小(χ2=299.718,P<0.001)、腋窝淋巴结状态(χ2=68.794,P<0.001)和组织学分级(χ2=7.572,P=0.023)是影响TNBC患者OS的相关因素;多因素分析中,Ki-67指数(HR=2.074,95%CI:1.279~3.364,P=0.003)、肿瘤大小(RR=1.879,95%CI:1.152~3.062,P=0.011)和腋窝淋巴结状态(RR=2.345,95%CI:1.825~3.015,P<0.001)是影响患者DFS的独立因素,Ki-67指数(RR=1.752,95%CI:1.020~3.008,P=0.042)、肿瘤大小(RR=20.011,95%CI:1.132~3.574,P=0.017)和腋窝淋巴结状态(RR=2.021,95%CI:1.517~2.693,P<0.001)是影响患者OS的独立因素.结论 Ki-67指数与TNBC患者预后相关,高Ki-67指数患者预后不良,Ki-67指数有望成为判断TNBC患者预后的一项重要生物学指标.     

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.     

Nomogram Based on Breast MRI and Clinicopathologic Features for Predicting Axillary Lymph Node Metastasis in Patients with Early-Stage Invasive Breast Cancer: A Retrospective Study

IntroductionTo establish a nomogram for predicting axillary lymph node (ALN) involvement in patients with early-stage invasive breast cancer (BC) based on magnetic resonance imaging (MRI) features and clinicopathological characteristics.Materials and MethodsPatients with confirmed early-stage invasive BC between 03/2016 and 05/2017 were retrospectively reviewed at the National Cancer Center/Cancer Hospital. Risk factors for ALN metastasis (ALNM) were identified by univariable and multivariable logistic regression analysis. The independent risk factors were used to create a nomogram.ResultsThis study included 214 early-stage invasive BC patients, including 57 (26.6%) with positive ALNs. Tumor location (OR = 4.019, 95% CI: 1.304 –12.383, P = .015), tumor size (OR = 3.702, 95%CI: 1.517 –9.034, P = .004), multifocality (OR = 3.534, 95%CI: 1.249 –9.995, P = .017), MR-reported suspicious ALN (OR = 9.829, 95%CI: 4.132 –23.384, P <0.001), apparent diffusion coefficient (ADC) value (OR = 0.367, 95%CI: 0.158 –0.852, P = .020), and lymphovascular invasion (LVI) (OR = 3.530, 95%CI: 1.483 –8.400, P = .004) were identified as independent risk factors associated with ALNM. A nomogram was created for predicting the probability of ALNM by using these risk factors. The calibration curve of the nomogram showed that the nomogram predictions are consistent with the actual ALNM rate. The area under the curve was 0.88 (95% CI: 0.83 –0.93). The nomogram had a bootstrapped-concordance index of 0.88 and was well-calibrated.ConclusionThe nomogram based on MRI and clinicopathologic features might be a useful tool for predicting ALNM in early-stage invasive BC and could help clinical decision-making.     

Association of high-sensitivity C-reactive protein and odds of breast cancer by molecular subtype: analysis of the MEND study

Breast cancer (BC) in Nigeria is characterized by disproportionately aggressive molecular subtypes. C-reactive protein (CRP) is associated with risk and aggressiveness for several types of cancer. We examined the association of high-sensitivity CRP (hsCRP) with odds of BC by molecular subtype among Nigerian women. Among 296 newly diagnosed BC cases and 259 healthy controls, multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association between hsCRP and odds of BC overall and by molecular subtype (luminal A, luminal B, HER2-enriched and triple-negative or TNBC). High hsCRP (> 3 mg/L) was observed in 57% of cases and 31% of controls and was associated with 4 times the odds of BC (aOR: 4.43; 95% CI: 2.56, 7.66) after adjusting for socio-demographic, reproductive, and clinical variables. This association persisted regardless of menopausal status and body mass index (BMI) category. High hsCRP was associated with increased odds of TNBC (aOR: 3.32; 95% CI: 1.07, 10.35), luminal A BC (aOR: 4.03; 95% CI: 1.29, 12.64), and HER2-enriched BC (aOR: 6.27; 95% CI: 1.69, 23.25). Future studies are necessary in this population to further evaluate a potential role for CRP as a predictive biomarker for BC.     

肺癌伴腋窝淋巴结转移患者临床特点分析

  目的  总结肺癌伴腋窝淋巴结转移（axillary lymph node metastasis,ALNM）的临床特点。  方法  回顾性分析2007年1月至2013年12月浙江省肿瘤医院收治的91例肺癌ALNM的患者资料。采用列联表分析原发灶、颈部和锁骨上区淋巴结、纵隔淋巴结与腋窝淋巴结位置相关性,采用Kaplan-Meier法计算总生存,以及不同时期发现ALNM患者的生存情况,并行Log-rank检验,进一步进行Cox回归分析。  结果  肺癌伴ALNM发生率为0.63%;常见于腺癌患者,以周围型病灶多见,常累及胸膜并伴胸水,或发生胸壁转移。原发灶、颈部和锁骨上区淋巴结、纵隔淋巴结与腋窝淋巴结位置存在相关性。肺癌伴ALNM的患者中位生存时间为19.02个月,2年生存率为62.64%。首诊伴ALNM患者生存情况差于首诊无腋窝淋巴结患者,且为独立预后因子（P=0.003,RR=2.18,95%CI:1.330~3.572）。  结论  肺癌伴ALNM发生率低,其可能的转移途径为胸壁、淋巴引流及血行转移,首诊发现ALNM的患者生存情况更差。      

Histopathological predictors of axillary lymph node metastases in patients with Breast Cancer

Background  A tumor 30 mm or less in diameter is a standard candidate for breast conserving surgery (BCS) in Japan. Axillary lymph node metastases (ALNM) is the most important prognostic factor for survival in patients with breast cancer, but the role of axillary node dissection has been controversial. Histopathological predictive factors of axillary lymph node involvement have not been established. The purpose of this study was to determine the association between the incidence of ALNM and histopathological factors by univariate and multivariate analysis. Methods  Sixty-five patients with noninvasive ductal carcinoma, and 993 patients with tumors 30 mm or less in diameter who underwent axillary dissection between 1988 and 1997 at our institute were reviewed. The association between ALNM and 13 histopathological factors (size, age, histological subtype, histological invasiveness, lymphatic invasion, vascular invasion, macroscopic classification, histological daughter mass, ductal spread, ER, PgR, p-53, and c-erbB-2) were analyzed by univariate and, when significant, by multivariate analysis. Results  Only one patient with noninvasive ductal carcinoma had ALNM, and 33.1% of 993 patients with a tumor 30 mm or less in size had ALNM. Multivariate analysis identified six factors as independent predictors for ALNM: lymphatic invasion, size, histological invasiveness, macroscopic classification, age and histological daughter mass. Conclusions  Axillary lymph node dissection can be omitted in patients with noninvasive ductal carcinoma. Histopathological features of tumors 30 mm or less in diameter can be used to estimate the risk of ALNM, and routine axillary node dissection might be spared in selected patients at minimal risk of ALNM, if the treatment decision is not influenced by lymph node status, such as in elderly patients.     

Androgenic pathway in triple negative invasive ductal tumors: Its correlation with tumor cell proliferation

Triple negative breast cancer (TNBC) is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 negativity. Patients with TNBC frequently undergo an aggressive clinical course due to the unavailability of specific targeted therapies. Androgen receptor (AR) was reported to be expressed in up to 60% of TNBC cases but there have been controversies as to the roles of androgen signaling through AR in TNBC. Therefore, in this study, we analyzed the status of AR in combination with androgen synthesizing enzymes (5α‐reductase type 1 (5αR1) and 17β‐hydroxysteroid dehydrogenase type 5 (17βHSD5)] in order to further understand androgenic actions in TNBC. Androgen receptor, 5αR1, and 17βHSD5 were immunolocalized in a cohort of 203 TNBC patients from Thailand and Japan. We then correlated the findings with clinicopathological characteristics (age, stage, tumor diameter, lymph node invasion, metastatic spread, Ki‐67 labeling index, disease‐free survival, and overall survival) of the patients. Univariate analysis revealed that AR+/enzyme+ cases were associated with a significantly lower Ki‐67 labeling index than AR?/enzyme? samples. Multivariate analysis indicated the presence of significant positive correlations between AR and enzyme status in tumor cells, and between tumor diameter, lymph node invasion, and distant metastasis. Significant negative correlations were also detected between Ki‐67 labeling index and AR status (P = 0.04) or 5αR1 (P < 0.001). Cox proportional hazards analysis showed that Ki‐67 labeling index and stage were the only factors predicting disease‐free and overall survival of the patients, although univariate Kaplan–Meier analysis revealed AR/5αR1 negativity suggested a more adverse clinical course up to 80 months after surgery. These results suggest that the presence of androgen synthesizing pathways in addition to AR expression in tumor cells could confer a better clinical outcome through suppression of cell proliferation.     

Frequency and Predictors of Axillary Lymph Node Metastases in Iranian Women with Early Breast Cancer

Background: Axillary lymph node metastasis is the most important predictive factor for recurrence risk andsurvival in patients with invasive breast carcinoma. The aim of this study was to determine factors associated withmetastatic involvement of axillary lymph nodes in Iranian women with early breast cancer. Methods: This article reportsa retrospective study of 774 patients with T1-T2 breast cancer who underwent resection of the primary tumor and axillarystaging by SLNB and/or ALND between 2005 and 2015 at our institution. Results: Of the 774 patients included in thisstudy, 35.5% (275 cases) had axillary lymph node involvement at the time of diagnosis. Factors associated with nodalinvolvement in univariate analyses were tumor size, lymphovascular invasion (LVI), tumor grade, ER/PR status andHER2 expression. All factors identified with univariate analyses were entered into a multivariate logistic regressionmodel and tumor size (OR= 3.01, CI 2.01–4.49, P <0.001), ER/PR positivity (OR = 1.74, CI 1.1.16–2.62, P = 0.007)and presence of LVI (OR = 3.3.8, CI 2.31–4.95, P <0.001) remained as independent predictors of axillary lymph nodeinvolvement .Conclusions: In conclusion, the results of this study suggests that positive hormonal receptor status, LVIand tumor size are predictive factors for ALNM in Iranian women with early breast cancer.     

Patient and provider characteristics that affect the use of axillary dissection in older women with stage I-II breast carcinoma

BACKGROUND: Axillary dissection for the evaluation and treatment of patients with breast carcinoma often is not performed in older women. The objective of this study was to examine patient, clinical, and surgeon characteristics associated with the use of axillary dissection after breast-conserving surgery (BCS). METHODS: A cohort of 464 women age > or = 67 years who were newly diagnosed with Stage I-II breast carcinoma and who underwent BCS were surveyed along with their 158 surgeons, and their medical records were reviewed. Patient, tumor, and provider characteristics were examined for association with the omission of axillary dissection. RESULTS: The majority of women (63.4%) underwent axillary lymph node dissection after BCS. Increasing age was associated strongly with decreasing odds of undergoing axillary lymph node dissection, even after considering patient health and preferences, clinical factors, and provider factors (odds ratio [OR], 0.11; 95% confidence interval [95%CI], 0.05-0.27). Independent of age and other factors, women in the lowest quartile of physical functioning were 37% less likely to undergo axillary lymph node dissection compared with women in the highest quartile (OR, 0.63; 95%CI, 0.62-0.64). Patients who were cared for by surgeons with subspecialty training in oncology were 60% less likely to undergo axillary lymph node dissection compared with patients who were cared for by other surgeons, even after considering other factors (OR, 0.41; 95%CI, 0.25-0.68). CONCLUSIONS: The results of this study demonstrated a correlation between lower use of axillary dissection and advancing age, lower functional status, and greater surgeon training. These findings suggest that simple, age-based considerations are important but are not the sole determinants of variations in treatment.     

PD-1及PD-L1在三阴性乳腺癌中差异性表达及与临床病理特征关系的研究

目的:探讨PD-1及PD-L1在三阴性乳腺癌（triple negative breast carcinoma,TNBC）中的表达情况。方法:收集158例TNBC组织标本,应用免疫组化方法进行PD-1及PD-L1的染色,观察其在TNBC中的表达情况,分析PD-1及PD-L1的表达与各项临床病理因素的关系。结果:PD-L1在TNBC肿瘤细胞及间质淋巴细胞中的表达率分别为53.2%和74.7%,PD-1在间质淋巴细胞中的表达率为64.6%;PD-L1与PD-1的表达有相关性（P＜0.05）;PD-L1及PD-1的表达与TNBC的肿瘤体积大、高组织学级别、基底样型BC（basal like breast carcinoma,BLBC）、Ki67增殖指数高及肿瘤浸润淋巴细胞（tumor infiltrating lymphocyte,TIL）高百分比相关（P＜0.05）,多因素回归分析提示肿瘤的大小、BLBC、Ki67高增殖指数及TIL高百分比是PD-L1和PD-1表达的危险因素;PD-L1及PD-1在伴髓样特征的癌、伴大汗腺特征的癌及化生性癌中高表达,在浸润性小叶癌、腺样囊性癌及腺泡细胞癌中不表达。结论:PD-L1及PD-1在TNBC中高表达,可以作为TNBC免疫治疗的靶标及预后标记物;肿瘤体积大、BLBC、Ki67增殖指数高及高TIL是PD-L1及PD-1表达的危险因素;PD-L1及PD-1表达在TNBC中存在组织学异质性。     

Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.     

EGFR、Ki67在三阴性与非三阴性乳腺癌中的表达及其与TNBC病理特征的相关性

目的 探讨EGFR、Ki67在三阴性与非三阴性乳腺癌中的表达差异及两者的表达与TNBC临床病理特征的关系.方法 分析non-TNBC与TNBC患者的临床病理资料,采用非生物素二步法检测76例乳腺癌标本里EGFR、Ki67的表达,对比两者在non-TNBC与TNBC中的区别.检测EGFR与Ki67在TNBC中的阳性表达率,研究其与病理参数的相关性.结果 和non-TNBC相比,TNBC多见于绝经前妇女,组织学分级较差,较易发生淋巴结转移、复发转移、远处转移,且出现较早.EGFR与Ki67在TNBC组织中的阳性表达率均高于在non-TNBC组织中的阳性表达率.EGFR、Ki67的表达与TNBC肿块直径、淋巴结转移情况、TNM分期、组织学分级之间均具有相关性.结论 EGFR与Ki67在TNBC中表达均升高.两者的表达与肿块直径、淋巴结转移情况、TNM分期、组织学分级之间均具有相关性.     

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.     

Association of the ARLTS1 Cys148Arg variant with familial breast cancer risk

Recently, ARLTS1 (ADP-ribosylation factor-like tumor suppressor gene 1) has been identified as a tumor suppressor gene, playing a major role in apoptotic signaling. The ARLTS1 Trp149Stop mutation has been shown to predispose to general familial cancer and high-risk familial breast cancer (BC), provoking the attenuation of apoptotic function. We studied the impact of the ARLTS1 Pro131Leu and Cys148Arg variants on high-risk familial and familial BC risk, investigating 482 familial BC cases (including 305 high-risk cases) and 530 control individuals. Unlike ARLTS1 Pro131Leu, Cys148Arg revealed a significant association with an increased risk of high-risk familial BC (odds ratio (OR)=1.47, 95% confidence interval (95% CI)=1.04-2.06, p=0.03) in a dose-dependent manner (ptrend=0.007). The genotype distribution of Cys148Arg in familial cases was similar, indicating significance as well (OR=1.48, 95% CI=1.10-1.99, p=0.009; ptrend=0.003). On the basis of the small number of 46 cases, we additionally showed an association between the Trp149Stop mutation and an increased risk of bilateral BC (OR=4.11, 95% CI=1.27-13.31, p=0.011).     

Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy

BACKGROUND: The current study identified determinants of systemic recurrence and disease-specific survival (DSS) in patients with early-stage breast carcinoma treated with breast-conserving surgery and radiation therapy (breast-conserving therapy, or BCT). METHODS: The study population consisted of 1,043 consecutive women with Stages I or II breast carcinoma who underwent BCT between 1970 and 1994. Clinical and pathologic characteristics evaluated included age, tumor size, tumor grade, estrogen and progesterone receptor status, surgical margins, axillary lymph node involvement, and use of adjuvant therapy. RESULTS: At a median follow-up time of 8.4 years, 127 patients (12%) had developed an ipsilateral breast tumor recurrence (IBTR), and 184 patients (18%) had developed a systemic recurrence. On multivariate logistic regression analysis, tumor size greater than 2 cm, positive lymph nodes, lack of adjuvant tamoxifen therapy, and positive margins (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.034) were predictors of systemic recurrence. When IBTR was added into the model, adjuvant therapy and surgical margins were not independent predictors; however, IBTR was an independent predictor of systemic recurrence (IBTR vs. no IBTR; OR, 6.2; 95% CI, 3.1-12.3; P < 0.001). The 10 year DSS rate after BCT was 87%. On multivariate Cox proportional hazards model analysis, the following factors were independent predictors of poor DSS: tumor size greater than 2 cm (vs. < or = 2 cm; relative risk [RR], 2.3; 95% CI, 1.2-4.3; P = 0.010), negative progesterone receptor status (vs. positive; RR, 2.7; 95% CI, 1.4-5.1; P = 0.003), positive margins (vs. negative; RR, 3.9; 95% CI, 1.4-11.5; P = 0.011), and IBTR (vs. no IBTR; RR, 5.5; 95% CI, 2.8-11.0; P < 0.001). CONCLUSIONS: Positive surgical margins and IBTR are predictors of systemic recurrence and disease-specific survival after BCT. Aggressive local therapy is necessary to ensure adequate surgical margins and to minimize IBTR.