Impact of smoking history on the outcomes of women with early-stage breast cancer: a secondary analysis of a randomized study

To assess the impact of smoking history on the outcomes of early-stage breast cancer patients treated with sequential anthracyclines–taxanes in a randomized study. This is a secondary analysis of patient-level data of 1242 breast cancer patients referred for adjuvant chemotherapy in the BCIRG005 clinical trial. Overall survival was assessed according to smoking history through Kaplan–Meier analysis. Univariate and multivariate Cox regression analyses of factors affecting overall and relapse-free survival were subsequently conducted. Factors that were evaluated included: age, performance status, number of chemotherapy cycles, T stage, lymph node ratio, estrogen receptor status, adjuvant radiotherapy and smoking history. Kaplan–Meier analysis of overall survival according to smoking status (ever smoker vs. never smoker) was conducted. There was a trend toward a better overall survival among never smokers compared to ever smokers; however, it was not statistically significant (P?=?0.098). The following factors were associated with better overall survival in multivariate analysis: older age (P?=?0.011), complete chemotherapy course (P?=?0.002), lower T stage (P?<?0.0001), lower lymph node ratio (P?<?0.0001) and positive estrogen receptor status (P?=?0.006). Otherwise, the following factors were associated with better relapse-free survival in multivariate analysis: older age (P?=?0.001), never smoking status (P?=?0.021), lower T stage (P?=?0.028), lower lymph node ratio (P?<?0.0001) and positive estrogen receptor status (P?<?0.0001). Early-stage breast cancer patients with a positive smoking history experienced worse relapse-free survival compared to never smokers. Physicians managing breast cancer patients should prioritize discussion about the benefits of smoking cessation when counseling their patients.     

Prognostic Markers for Invasive Micropapillary Carcinoma of the Breast: A Population-Based Analysis

BackgroundInvasive micropapillary carcinoma (IMPC) is a rare and distinct variant of breast carcinoma with a high propensity for regional lymph node involvement. Because of its lymphotropic nature, IMPC is considered to have an unfavorable prognosis when compared with invasive ductal carcinoma (IDC).Patients and MethodsThis study of 624 patients diagnosed with breast IMPC (2001-2008) listed in the National Cancer Institute's Surveillance, Epidemiology, and End Results (NCI SEER) database was performed to evaluate prognostic factors for disease-specific survival (DSS) and overall survival (OS).ResultsThe 5-year DSS and OS for patients with IMPC were 91.9% and 83.8%, respectively. Of those with known estrogen receptor (ER) status, 84.8% were ER-positive (ER⁺), which was associated with better DSS (hazard ratio [HR], 0.27; P < .0002) and OS (HR 0.45; P < .006). At presentation, 52.9% of the patients with lymph node examinations had nodal involvement and 4.1% had distant metastases. Patients with 4 or more positive lymph nodes had worse DSS (HR 6.43; P = .0013) and OS (HR 3.47; P = .00067) than did patients with node-negative disease, but those with 1 to 3 positive lymph nodes had DSS and OS similar to those of patients with node-negative disease.ConclusionAlthough IMPC has a high propensity for lymph node metastasis, it has a DSS and overall prognosis comparable to those of IDC. Patients with ER-negative (ER?) disease or those with 4 or more positive lymph nodes have the worst prognosis. This is the largest study of IMPC to date, and these findings will help address some of the inconsistencies regarding this rare histologic variant of breast cancer.     

High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival

YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum YKL-40 in patients with metastatic breast cancer and colorectal cancer is associated with a poorer prognosis as compared to patients with normal serum YKL-40. In the present study we evaluated the associations of preoperative serum YKL-40 in 271 patients with primary breast cancer in relation to relapse-free survival and overall survival. The median follow-up time was 5.9 years. There were 77 relapses and 69 patients died. The median serum YKL-40 concentration in the patients was 57 µg/l (range 22–688 µg/l) and significantly elevated (p < 0.0001) compared to serum YKL-40 in healthy females. Nineteen percent of the patients had high serum YKL-40 (i.e., > 95 percentile of healthy females). Patients with high serum YKL-40 had shorter relapse-free interval (hazard ratio (HR) = 1.77, 95% confidence interval (CI): 1.06–2.95, p = 0.028) and overall survival (HR = 1.78, 95% CI: 1.04–3.05, p = 0.036) than patients with normal serum YKL-40. Serum YKL-40 was higher (p = 0.005) in lymph node positive patients as compared to lymph node negative patients. Multivariate analysis including lymph node status, estrogen receptor status, tumor size, age, menstrual status and serum YKL-40 showed that serum YKL-40 was an independent prognostic variable of relapse-free survival (HR = 1.73, 95% CI: 1.03–2.91, p = 0.039). Our results show that serum YKL-40 in patients with primary breast cancer at time of operation is only elevated in a small group of patients, but these patients have a shorter recurrence free interval. Further studies are required to determine the biological function of YKL-40 in breast cancer.     

２９３例乳腺癌患者术后预后因素分析

目的：探讨２９３例乳腺癌患者月经情况、术后Ｔ分期、Ｎ分期、受体、术后放疗、化疗及内分泌治疗等因素对患者无病生存时间及总生存时间的影响。方法：收集我院２００２～２００６年２９３例乳腺癌患者术后的完整随访资料,选择可能对乳腺癌术后患者预后产生影响的非重复特征因素,包括月经情况、术后病理的Ｔ分期、Ｎ分期、受体的免疫组化分型、术后放疗、化疗及内分泌治疗,采用Ｃｏｘ风险回归模型分析影响无复发生存率（ＲＦＳ）和总生存率（ＯＳ）的预后因素。对具有统计学意义的独立预后因素进行分层分析及Ｋａｐｌａｎ Ｍｅｉｅｒ生存曲线分析。结果：本组病例中Ｎ分期是影响患者ＲＦＳ及ＯＳ的独立因素,相对危险度（ＯＲ）分别为１.４５３（９５％ＣＩ：１.０９６～１.９２６,Ｐ＜０.０１）、１.４５８（９５％ＣＩ：１.０９９～１.９９３,Ｐ＜０.０１）。对Ｎ分期进行分层分析及Ｋａｐｌａｎ Ｍｅｉｅｒ生存曲线分析表明,Ｎ０期患者的ＲＦＳ及ＯＳ优于Ｎ１～Ｎ３期患者（Ｐ＜０.０５）,而Ｎ１～Ｎ３期患者之间ＲＦＳ及ＯＳ无差异（Ｐ＞０.０５）。结论：乳腺癌术后患者Ｎ分期与患者的预后有关,淋巴结阴性患者的预后好于淋巴结阳性患者预后,建议对淋巴结阳性患者加强术后辅助治疗。     

Epidermal growth factor receptor expression as a prognostic indicator in breast cancer

The significance of epidermal growth factor receptor (EGFR) status as a prognostic indicator was investigated by a competitive binding assay in 135 primary breast cancer patients. 55 patients (41%) were EGFR positive and EGFR status was negatively correlated with oestrogen receptor (ER) status (P < 0.01). 5-year postoperative follow-up showed that relapse-free survival for EGFR positive patients was significantly worse than that for EGFR negative patients (P < 0.05). There was no difference between the two groups in tumour size, axillary node involvement, age and menopausal status. Analysis by axillary node status demonstrated the poor prognosis of the EGFR positive group in node positive patients. As yet, no difference in prognosis has been seen in node negative patients. A higher frequency of haematopoietic relapse was observed in EGFR positive patients. Simultaneous or sequential EGFR measurements in primary tumour and metastatic sites of 34 patients showed that expression of EGFR was more enhanced in metastatic sites.     

The prognostic value of the mitotic activity index in patients with primary breast cancer who were not treated with adjuvant systemic therapy

Background. At the St Gallen meeting of 2001 it was agreed to select high-risk patients for adjuvant systemic therapy by lymph node status, tumor size, age, hormone receptor status, and histological grade. In The Netherlands it was chosen to use either the histological grade or the mitotic activity index (MAI). The aim of this study was to retrospectively evaluate the independent prognostic value of the MAI in primary breast cancer patients, who were not treated with adjuvant systemic therapy, on relapse-free survival (RFS) and overall survival (OS). Patients and methods. The data of 137 systemically untreated patients with primary breast cancer diagnosed between 1992 and 1996, of whom MAI was assessed, were retrospectively collected. The MAI was correlated to classical prognostic factors and we determined the prognostic value of the MAI, the histological grade and other prognostic factors. Results. The median observation time was 4.2 years. The MAI showed a positive correlation to lymph node status (P <; 0.001) and a negative correlation to age (P = 0.005), menopausal status (P <; 0.001) and the ER and PgR status (r _s = –0.390 [ER], r _s = –0.440 [PgR], both P < 0.001). A high MAI ( 15) predicted a reduced RFS and OS in the Kaplan–Meier analysis (P = 0.0070 and P = 0.0017, respectively). Also in the multivariate analysis, the MAI showed to be an independent predictor of poor RFS (P = 0.035), in addition to lymph node status. However, the MAI did not predict for OS, in contrast to tumor size and lymph node status. Conclusion. The present study confirms that the MAI is an independent prognostic factor for RFS, but not for OS and may be useful for daily clinical practice.     

The detection and analysis of estrogen and progesterone receptors in breast cancer (report of 1,393 patients)

Objective To explore the distribution of estrogen receptors (ER) and progesterone receptors (PR) in patients with breast cancer and to compare the results with clinical parameters. Methods Breast cancer specimens of 1393 cases were stained for the ER and PR by a SP Two -Step method, and analyzed with respect to age, menstrual status, histopathology and metastasis of axillary lymph nodes. Results The correlation coefficients between ER and PR were positive-(P< 0.0001). The negative expression of ER in patients 39 years or less was the highest with a statistical significance (P<0.0001 ). There was no relationship between the patient’s age and positive expression of ER, PR and negative expression of PR (P>0.05). There were significantly higher positive rates of ER and lower positive rates of PR in post-menopausaf patients than in pre -menopausal cases(P<0.0001). There was no relationship between the status of ER, PR and the corresponding histopathology (P>0.05). The patients with no metastasis in the axillary lymph nodes had higher simultaneous positive rates of ER and PR (P<0.0001), and those with axillary lymph node metastasis had significantly higher rates of negative expression of ER and PR(P<0.0001). Conclusion The positive and negative distributions of ER and PR have some regular patterns which may be used as a reference to choose combined therapy and to predict the prognosis for breast cancer patients.     

Operable Breast Cancer： a Clinical Analysis of 6,263 Cases

OBJECTIVE In Europe and America breast cancer commonly occurs in women of middle and old age, with a median age of about 57 years. Modified radical mastectomy now called standard radical mastectomy, has taken the place of traditional radical mastectomy. Patients with breast cancer at an early stage commonly receive BCT (breast conservative therapy). The TNM stage (especially the lymph node status) affects the prognosis, and adjuvant therapy can improve survival. In China, only a few reports have been pubIished studying large numbers of breast cancer patients. This study was designed to analyze the clinical features, surgical pattern and treatment outcome of resectable breast cancer, as well as to explore the prognostic factors and the effect of adjuvant therapy, with a goal to improve the level of diagnosis and treatment.METHODS Records of the 6,263 patients with resectable breast cancer who had been admitted into our hospital from June 1964 to June 2003 were analyzed retrospectively.RESULTS Of the 6,263 cases, 98.8% were female. Breast cancer occurred most frequently in patients of ages 40～49 years (41.0%), especially in patients 45～49 years old (25.2%). A breast lump, which occurred in 96.2% of the patients, was the main clinical manifestation. The overall 5- and 10-year survival rates were 75.16% and 40.44%. Of the patients in TNM stages 0-1,Ⅱ, and Ⅲ, the 5-year survival rates were 96.8%, 73.7% and 46.4% respectively and the 10-year survival rates were 78.7%, 64.6% and 33.5% respectively. The 5-, and 10-year survival rates were higher in the lymph node negative group than in the lymph node positive group (80.3% vs. 55.6%, and 59.2% vs. 31.9%, P＜0.01). Since the 1980s there was no significant difference in survival rates of patients who received a radical mastectomy compared to a modified radical mastectomy(P＞0.05). Of the 73 patients who underwent breast conservative therapy, no local recurrence or metastasis occurred during a maximal follow-up of 17 years. Of the patients in stage T2T4, the 5-, and 10-year survival rates were significantly higher in the group treated with adjuvant chemotherapy compared to the non-chemotherapy group (78.2% vs. 60.1%, and 48.9% vs. 30.7%, P＜0.01).CONCLUSION According to our data, breast cancer most frequently occurred in patients of ages 45～49 years. The TNM stage (especially the lymph node status) relates to breast cancer prognosis. The prognosis was worse in patients with positive lymph nodes compared to the patients with negative lymph nodes. The efficacy of a modified radical mastectomy is equal to that of a radical mastectomy, and breast conservative therapy can be applied to patients in an early stage. Adjuvant chemotherapy and endocrine therapy can improve the survival of resectable breast cancer patients.     

表皮生长因子受体表达与乳腺癌激素受体水平和预后的关系

应用免疫组化ＡＢＣ方法研究７５例乳腺癌冰冻组织表皮生长因子受体（ＥＧＦＲ）的表达，结合临床资料和ＥＲ、ＰＲ测定结果进行分析，探讨ＥＧＦＲ表达与乳腺癌预后的关系。结果表明，ＥＧＦＲ阳性３０例（４０％），ＥＧＦＲ表达与肿瘤大小、腋淋巴结状况，临床分期和年龄无关，与ＥＲ、ＰＲ存在着显著的负相关（Ｐ＜０．００５）。全组中位随诊时间为６０个月，ＥＧＦＲ阳性组术后总生存率明显低于阴性组（Ｐ＜０．００１）。在无腋淋巴结转移的病例中，ＥＧＦＲ阳性组和阴性组术后生存情况也有显著差异（Ｐ＜０．０１），提示ＥＧＦＲ表达与乳腺癌不良的预后有关。调整分析乳腺癌有关的预后因素，各组病例中均以ＥＧＦＲ表达阳性组的预后为差，说明ＥＧＦＲ对乳腺癌预后具有独立的作用，不受其他因素的影响。经Ｃｏｘ模型多因素分析显示，ＥＧＦＲ和腋淋巴结受累与否是对乳腺癌术后生存情况有显著性影响的两个因素。     

Higher Ki67 Expression is Associates With Unfavorable Prognostic Factors and Shorter Survival in Breast Cancer

Background: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of thisstudy was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2and hormone receptor expression status in breast cancers. Materials and Methods: Clinical and pathologicalfeatures of the patients with breast cancer were retreived from the hospital records. Results: In this study, 163patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20%and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001),estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymphnode positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free andoverall survival compared to those of higher Ki67 levels. Conclusions: High Ki67 expression is associated withER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The levelof Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.     

Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial

BackgroundPreoperative histologic examination of tumour tissue is essential when deciding if endometrial cancer surgery should include lymph node sampling. We wanted to investigate if biomarkers could improve prediction of lymph node metastasis and outcome.Patients and methodsCurettage specimens from 832 endometrial carcinoma patients prospectively recruited from 10 centres in the MoMaTEC trial (Molecular Markers in Treatment of Endometrial Cancer) were investigated for hormone receptor and p53 status.ResultsEighteen per cent of tumours were double negative for oestrogen- and progesterone receptors (ER/PR loss), 24% overexpressed p53. Pathologic expression of all markers correlated with nodal metastases, high FIGO (Federation International of Gynecology and Obstetrics) stage, non-endometrioid histology, high grade and poor prognosis (all P < 0.001). ER/PR loss independently predicted lymph node metastasis (odds ratios (OR) 2.0, 95% confidence interval (CI) 1.1–3.7) adjusted for preoperative curettage histology and predicted poor disease-specific survival adjusted for age, FIGO stage, histologic type, grade and myometrial infiltration (hazard ratio (HR) 2.3, 95% CI 1.4–3.9). For lymph node negative endometrioid tumours, ER/PR loss influenced survival independent of grade.ConclusionDouble negative hormone receptor status in endometrial cancer curettage independently predicts lymph node metastasis and poor prognosis in a prospective multicentre setting. Implementing hormone receptor status to improve risk-stratification for selecting patients unlikely to benefit from lymphadenectomy seems justified.     

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.     

Prognosis of Node-Positive Breast Cancer Patients Who Underwent Parasternal Lymph Node Biopsy During Surgery Followed by Doxorubicin- or Mitoxantrone-Containing Adjuvant Chemotherapy

Abstract

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.     

Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: Long-term follow up on IBCSG Trial IX

BackgroundThe benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed.Patients and methodsAfter stratification by ER status, 1669 postmenopausal patients with operable lymph node-negative breast cancer were randomly assigned to three 28-day courses of ‘classical’ CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF→tamoxifen) or to tamoxifen alone for 5 years.ResultsERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF→tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes.ConclusionCMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy.     

The Detection and Analysis of Estrogen and Progesterone Receptors in Breast Cancer （Report of 1,393 Patients）

Objective  To explore the distribution of estrogen receptors (ER) and progesterone receptors (PR) in patients with breast cancer and to compare the results with clinical parameters. Methods  Breast cancer specimens of 1393 cases were stained for the ER and PR by a SP Two -Step method, and analyzed with respect to age, menstrual status, histopathology and metastasis of axillary lymph nodes. Results  The correlation coefficients between ER and PR were positive-(P< 0.0001). The negative expression of ER in patients 39 years or less was the highest with a statistical significance (P<0.0001 ). There was no relationship between the patient’s age and positive expression of ER, PR and negative expression of PR (P>0.05). There were significantly higher positive rates of ER and lower positive rates of PR in post-menopausaf patients than in pre -menopausal cases(P<0.0001). There was no relationship between the status of ER, PR and the corresponding histopathology (P>0.05). The patients with no metastasis in the axillary lymph nodes had higher simultaneous positive rates of ER and PR (P<0.0001), and those with axillary lymph node metastasis had significantly higher rates of negative expression of ER and PR(P<0.0001). Conclusion  The positive and negative distributions of ER and PR have some regular patterns which may be used as a reference to choose combined therapy and to predict the prognosis for breast cancer patients.     

肥胖乳腺癌患者的临床特征及预后的回顾性研究(英文)

Objective:The aim of our study was to investigate the prognosis of obese breast cancer patients.Methods:This study was conducted on a total of 317 breast cancer patients who were histopathologically and clinically diagnosed at the General Hospital of Shenyang Military Region(China)from 2004 to 2006.Clinical data including height,weight,age at diagnosis,tumor size,lymph node status,menopausal status,family history of cancer and hormone receptor status were collected.Log-rank test was performed to compare the disease free survival(DFS)and overall survival(OS).Cox proportional hazards regression analysis was conducted to make multivariate analysis.The Chi square test was used to compare the clinical features among normal weight group,overweight group,and obese group.Results:Obesity was an independent prognostic factor for DFS(P=0.022)and OS(P=0.032)in breast cancer patients.In the stratified analysis based on the hormone receptor status,obesity was independently associated with OS in patients with negative ER/PR(P=0.002),but such association was not observed in patients with positive hormone receptors.Obesity was also associated with lymph node status(P=0.001)and smoking(P=0.009).Conclusion:Obesity is associated with poor DFS and OS in patients with breast cancer.Therefore,maintaining normal weight may benefit breast cancer patients.     

Overexpression of AIB1 negatively affects survival of surgically resected non-small-cell lung cancer patients

BackgroundThe amplified in breast cancer 1 (AIB1) gene has been considered to play an oncogenic role in human cancers, but its clinical/prognostic significance in non-small-cell lung cancer (NSCLC) is still unclear.Patients and methodsThe methods of immunohistochemistry and FISH were utilized to examine protein expression and amplification of AIB1 in 230 informative surgically resected NSCLCs and in 30 samples of normal lung tissues.ResultsOverexpression and amplification of AIB1 were found in 48.3% and 8.2% of NSCLCs, respectively. AIB1 overexpression was associated with AIB1 gene amplification and cell proliferation but not related to estrogen receptor (ER)-α, ER-β, progesterone receptor or androgen receptor status. A positive correlation between AIB1 overexpression and an ascending pathologic node stage in lung adenocarcinoma (ADC) was observed (P = 0.043). Univariate survival analysis demonstrated a significant association of AIB1 overexpression with shortened patient survival, especially for those with stage III disease (P < 0.001). Importantly, AIB1 expression was evaluated as the most significant predictor for survival in multivariate analysis (hazards ratio = 2.069, P < 0.001).ConclusionOverexpression of AIB1 might provide a selective advantage for lymph node metastasis of lung ADC and serve as a useful biomarker for poor prognosis for NSCLC patients.     

Phosphorylation of estrogen receptor-alpha at Ser167 is indicative of longer disease-free and overall survival in breast cancer patients.

PURPOSE: Ser(167) was first identified as a major phosphorylation site of the estrogen receptor -alpha (ER) positive in the MCF7 breast cancer cell line. Subsequent studies have shown that Ser(167) phosphorylation is important in the regulation of ER activity and have identified p90RSK and AKT as protein kinases that phosphorylate Ser(167). The purpose of this study was to determine the importance of Ser(167) phosphorylation in breast cancer progression. EXPERIMENTAL DESIGN: Immunohistochemical staining of primary breast cancer biopsies (n = 290) was carried out using antibodies specific for ER phosphorylated at Ser(167) and for phosphorylated p44/p42 mitogen-activated protein kinase (MAPK), phosphorylated p90RSK, and phosphorylated AKT. RESULTS: In ER-positive breast cancer patients, Ser(167) phosphorylation was associated with low tumor grade (P = 0.011), lymph node negativity (P = 0.034), and relapse-free (P = 0.006) and overall (P = 0.023) survival. Further, Ser(167) phosphorylation was strongly associated with phosphorylated p90RSK (P < 0.001), previously shown to phosphorylate Ser(167) in vitro, as well as being associated with phosphorylated MAPK (P < 0.0005). The activities of both kinases also seemed to be indicative of better prognosis. There was, however, no association between HER2 positivity and Ser(167) phosphorylation nor were the activities of MAPK or p90RSK associated with HER2 status, suggesting that other cell surface receptors may be important in regulating these activities in breast cancer. CONCLUSIONS: These findings show that phosphorylation at Ser(167) of ER predicts for likelihood of response of ER-positive breast cancer patients to endocrine therapies.     

284例原发乳腺癌c-erbB2蛋白的表达及其与预后的关系

目的探讨c-erbB2癌蛋白在原发乳腺癌组织中的表达情况及其与预后的关系。方法采用免疫组化SP法检测284例原发乳腺癌组织的c-erbB2表达,并用统计学分析其与预后的关系。结果284例原发乳腺癌c-erbB2的阳性表达率为26．8％（76／284）,其表达与淋巴结转移数目（P=0．003）密切相关。单因素分析表明,c-erbB2是总生存时间（OS,P=0．002）和无病生存时间（DFS,P=0．024）的重要预后因素;多因素分析表明,c-erbB2是影响Os（P=0．023）的独立预后因素。此外,c-erbB2阳性的肿瘤患者较阴性者更易于发生内脏转移。而对于不同的淋巴结转移和ER状态,c-erbB2也有不同的预后价值。结论c-erbB2是影响原发乳腺癌患者OS的独立因素;在不同的淋巴结转移和ER状态下,其预后价值不同。     

乳腺肿瘤分子亚型与预后的关系

目的 探讨乳腺肿瘤不同分子亚型临床特点及其与预后的关系.方法 选择有明确免疫组织化学检测的716例患者,根据雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER-2)的表达情况,将乳腺肿瘤分为4种分子亚型,即Luminal A型、Luminal B型、HER-2过表达型和basal-like型,回顾性分析各分子亚型的临床特征、复发转移、预后情况及影响预后的因素.结果 716例患者中,各分子分型在年龄、绝经状况、产次、临床分期及是否放疗的差异无统计学意义(均P＞0.05),在腋窝淋巴结转移(x2=17.208,P=O.001)、肿瘤最大直径(x2=20.528,P=0.000)、手术方式(x2=24.242,P=0.000)、化疗方案(x2=10.711,P=O.013)的差异具有统计学意义.临床分期(x2=17.005,P=0.002)、腋窝淋巴结转移(x2=11.267,P=0.000)及分子分型(x2=125.634,P=0.000)是影响乳腺肿瘤患者长期生存率的独立预后因素.结论 不同分子分型乳腺肿瘤长期生存率不同,basallike型长期生存率最低,乳腺肿瘤的分子分型对判断患者预后具有重要意义.