Retrospective Analysis of Neoadjuvant Chemotherapy for Breast Cancer in Turkish Patients

Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advancedbreast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials andconsequently are widely used. In this study aimed to research the complete response (pCR) rates in differentregimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This studyincluded 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvantchemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response toneoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumorin the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesteronereceptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor wasdefined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumorER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14(min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal.Staging was performed postoperatively based on the pathology report and appropriated imaging modalitiesThe TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven(90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade IIand 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. Thepatients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response tochemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 anddoxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCRwas higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the groupthat treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Someother factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentageof ER positivity, and HER2 expression.     

Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer

Prior studies have suggested a higher prevalence of high grade, ER-negative, HER2-positive, and basal-like carcinomas in young women with breast cancer. However, the precise distribution of poor prognostic features in this population remains unclear. We examined the pathologic features and distribution of molecular phenotype in relation to patient age in a large group of young women (≤40?years) with invasive breast cancer. Medical records were reviewed for clinical characteristics, tumor stage, and receptor status. Pathologic features, including those features associated with basal-like carcinomas, were examined by central review. Using tumor grade and biomarker expression, cancers were categorized as luminal A (ER+ and/or PR+ and HER2-, histologic grade 1 or 2); luminal B (ER+ and/or PR+ and HER2+, or ER and/or PR+, HER2- and grade 3); HER2 (ER and PR- and HER2+); and triple negative (ER-, PR-, and HER2-). Among 399 women?of ≤40?years, 33% had luminal A tumors, 35% luminal B, 11% HER2 (ER-negative), and 21% triple negative. Compared to published results for all breast cancers, a greater proportion of young women had luminal B tumors, and a lesser proportion had luminal A. There were no significant differences in molecular phenotype, tumor stage or grade among the different age groups of young women. However, this population of young women presented with a different distribution of molecular phenotypes compared to the general population of women with breast cancer. These findings may have implications with regard to the etiology and prognosis of breast cancer in young women.     

Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients

Estrogen receptor status in breast cancer is associated with response to hormonal therapy and clinical outcome. The additional value of progesterone receptor (PR) has remained controversial. We examine the value of PR for prognosis and response to tamoxifen on a population-based series of 4,046 invasive early stage breast cancer patients. Clinical information for age at diagnosis, stage, pathology, treatment and outcome was assembled for the study cohort; the median follow-up was 12.4 years. PR status was determined by immunohistochemistry using a rabbit monoclonal antibody on tissue microarrays built from breast tumor surgical excisions. Survival analyses, Kaplan–Meier functions and Cox proportional hazards regression models were applied to assess the associations between PR and breast cancer specific survival. Progesterone receptor was positive in 51% of all cases and 67% of estrogen receptor positive (ER+) cases. Survival analyses for both the whole cohort and ER+ cases given tamoxifen therapy showed that patients with PR+ tumors had 24% higher relative probability for breast cancer specific survival as compared to PR− patients, adjusted for ER, HER2, age at diagnosis, grade, tumor size, lymph node status and lymphovascular invasion covariates. Higher PR expression showed stronger association with patient survival. Log-likelihood ratio tests of multivariate Cox proportional hazards regression models demonstrated that PR was an independent statistically significant factor for breast cancer specific survival in both the whole cohort and among ER+ cases treated with tamoxifen. PR adds significant prognostic value in breast cancer beyond that obtained with estrogen receptor alone.     

乳腺癌组织中lncRNA CCHE1水平及其临床意义

目的探讨长链非编码RNA（lncRNA）CCHE1在乳腺癌组织中的表达及其临床意义。 方法收集本院2011年1月至2012年12月切除的乳腺癌组织115例和配对癌旁组织78例,采用实时荧光定量PCR（QPCR）检测CCHE1在上述组织中的表达情况,比较乳腺癌组织和癌旁组织中的CCHE1水平;分析CCHE1水平与乳腺癌临床病理参数（年龄、临床T分期、组织学分级、淋巴结转移、Nottingham预后指数、Ki 67增殖指数、ER表达、PR表达及HER 2扩增）和复发的关系;分析不同CCHE1水平的总生存期（OS）和无进展生存期（PFS）,采用Cox比例风险模型进行多因素分析。 结果QPCR检测发现,115例乳腺癌组织中的CCHE1水平为7610±3210,高于癌旁组织的2142±1753（P＜005）。CCHE1水平与临床T分期、淋巴结转移、Nottingham预后指数、HER 2扩增和肿瘤复发有关（P＜005）,而与年龄、组织学分级、ER表达、PR表达和Ki 67增殖指数无关（P＞005）。CCHE1低表达组的中位PFS和OS分别为560个月和630个月,均优于高表达组的370个月和420个月（P＜005）;CCHE1水平、临床T分期、淋巴结转移、Nottingham预后指数和HER 2扩增是影响OS和PFS的独立预后因素（P＜005）。 结论CCHE1在乳腺癌组织中表达升高,该lncRNA可能在乳腺癌的发生、发展中有一定作用,可作为潜在地评估乳腺癌患者预后的分子标志物。     

Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change

Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen-associated density change. This biopsy-based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double-blinded tamoxifen dose-determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound-guided core-needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1–20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2-fold higher PR expression compared to non-responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen-associated density decrease, and that the age-associated difference in density change may be related to age-dependant differences in expression of Ki67 and PR.     

MACC1及其靶蛋白SPON2在乳腺癌中的表达及与预后的关系

目的:探讨结肠癌转移相关基因1（metastasis-associated in colon cancer 1,MACC1）及其靶蛋白SPON2在乳腺癌组织中的表达及与临床病理因素的相关性,并评估它们对乳腺癌患者预后的影响。方法:收集2011年1月至2011年12月间于同济医院行乳腺癌根治术的126例乳腺癌患者的癌和相应癌旁组织石蜡标本,应用免疫组化Envision法检测MACC1和SPON2蛋白在癌及癌旁组织中的表达,分析MACC1和SPON2表达与乳腺癌临床病理特征及患者预后的关系。结果:MACC1主要定位于细胞质及细胞膜,SPON2在细胞膜、细胞质及细胞外基质中出现表达,MACC1和SPON2蛋白在乳腺癌组织中的表达均明显高于癌旁组织（68.3% vs 21.4%和71.4% vs 17.5%,P均<0.01)。MACC1表达与乳腺癌患者组织学分级、TNM 分期、淋巴结转移、肿瘤复发显著相关（P均<0.05）;SPON2表达与患者TNM分期、淋巴结转移、Nottingham预后指数、肿瘤复发显著相关（P均＜0.05）;二者均与ER、PR及HER2状态无关（P>0.05）,且乳腺癌组织中MACC1和SPON2的表达呈显著正相关（P＜0.001）。Kaplan-Meier生存曲线显示,MACC1和SPON2高表达的患者总生存期（OS）和无进展生存期（PFS）均较短（P均<0.001）;Cox比例风险模型分析表明,MACC1和SPON2过表达是乳腺癌患者预后的独立影响因素（P均＜0.001）。结论:MACC1和SPON2可能参与了乳腺癌的发生、发展,在乳腺癌预后评估中具有一定价值,可能成为潜在的靶点为乳腺癌治疗提供一些新的思路。     

乳腺癌组织HR与HER-2和SATB1表达相关性研究

目的：检测乳腺癌组织中激素受体（hormonereceptor,HR）、人表皮生长因子受体2（humanepidermalgrowthfactOrreceptor2,HER-2）和特异性核基质结合蛋白（specialATrichsequencebindingprotein1,SATB1）的表达,探讨HR与HER-2、SATB1及临床病理参数的关系。方法：应用免疫组织化学方法检测乳腺癌患者雌激素受体（estrogenre-ceptor,ER）、孕激素受体（progesteronereceptor,PR）、HER-2及SATB1蛋白的表达,荧光原位杂交方法检测HER-2基因扩增状态,统计学方法分析HR（包括ER及PR）的表达与HER-2、SATB1及临床病理参数之间的相关性。结果：乳腺癌组织ER及PR的表达均与患者年龄正相关（r=0．286,P=0．010;r=0．249,P=0．026）,ER的表达与肿瘤分级负相关（r=-0．306,P=0．006）;ER及PR的表达与肿瘤大小、组织学类型、淋巴转移情况及TNM分期均无明显相关性,P值均〉0．05。HR的表达与SATB1、HER-2及SATB1／HER2双阳性表达均呈负相关关系（r=-0．248,P=0．027;r=-0．392,P〈0．001;r=-0．150,P〈0．001）。结论：HR阳性患者治疗及预后相对较好;乳腺癌组织HR的表达与HER-2和SATB1呈负相关关系,三者之间可能存在相互联系的信号通路。     

Prognostic utility of fluorescence in situ hybridization for determining HER2 gene amplification in breast cancer

An accurate investigation of the HER2 proto-oncogene is extremely important for the therapy and prognostication of breast cancer. Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are standard methods for this purpose. The aim of this study was to detect the expression and amplification of HER2 in paraffin-embedded samples of breast cancer tissue and to investigate the relationship between HER2 amplification and various clinicopathological parameters in advanced breast cancers. We used FISH to examine the HER2 gene amplification and IHC to examine the expression of HER2 protein, estrogen receptor (ER) and progesterone receptor (PR) in 62 advanced breast cancers. HER2 gene amplification was detected by FISH in 12 breast cancers (19%) and HER2 protein expression with a score of 3+ was detected by IHC in 11 (17%). There was a significant correlation between the HER2 gene amplification and HER2 protein overexpression in breast cancers (P<0.0001). However, some mismatching was evident: 3 cases, negative for the HER2 gene, showed a HER2 protein expression score of 3+ and 2 cases, positive for HER2 gene amplification, had HER2 protein expression scores of 0 and 1+ (negative), respectively. ER and PR were expressed in 41 (66%) and 46 (74%) cancers, respectively. No correlation was observed between the HER2 gene amplification and any of the clinicopathological parameters examined, including age, histopathological type, TNM stage, tumor size, lymph node status, relapse and expression of PR. We observed three patterns among the 6 deceased cases: i) triple negativity for HER2, ER and PR, ii) positivity for HER2 gene amplification with a mismatching HER2 protein expression, and iii) positivity for the HER2 gene amplification with a matching HER2 protein expression score of 2+ or 3+. The triple negative cases and HER2 gene amplification positive cases with a mismatching HER2 protein expression had a poor outcome. These results suggest that in breast cancer, the detection of HER2 gene amplification by FISH is desirable compared with the HER2 protein expression determined by IHC. Moreover, triple negativity for HER2, ER and PR is a potentially very important prognostic marker.     

A review of an unfavorable subset of breast cancer: estrogen receptor positive progesterone receptor negative

Estrogen receptor (ER)(+) progesterone receptor (PR)(-) tumors are a distinct subset of breast cancers characterized by aggressive behavior and tamoxifen resistance in spite of being ER(+). They are categorized as luminal B tumors and have greater genomic instability and a higher proliferation rate. High growth factor (GF) signaling and membranous ER activity contribute to the aggressive behavior of these tumors. The absence of PR is attributable to low serum estrogen, low levels of nuclear ER, and features of molecular crosstalk between GFs and membranous ER. PR expression is also downregulated by expression of mutated epidermal growth factor receptor (EGFRvIII). This subset of patients has greater expression of human epidermal growth factor receptor (HER)-1 and HER-2 and active GF signaling mediated by the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin pathway. Currently, aromatase inhibitors, fulvestrant, and chemotherapy may be the favored treatment approaches for this subset of patients. Overcoming tamoxifen resistance with targeted therapies such as gefitinib is being evaluated and strategies involving short courses of tamoxifen have been postulated for prevention of recurrence of this subtype. Understanding the interplay between molecular endocrinology and tumor biology has provided experimental therapeutic insights, and continued work in this area holds the promise of future advances in prognosis.     

The prognostic biomarkers HOXB13, IL17BR, and CHDH are regulated by estrogen in breast cancer.

PURPOSE: We previously identified three genes, HOXB13, IL17BR, and CHDH, that strongly predict clinical outcome in estrogen receptor (ER)-positive breast cancer patients receiving tamoxifen monotherapy. The biological mechanisms linking these genes to estrogen signaling and tamoxifen response in breast cancer remain to be determined. EXPERIMENTAL DESIGN: In a consecutive series of 148 ER-positive and ER-negative breast cancers, HOXB13, IL17BR, and CHDH gene expression was measured by quantitative real-time PCR and correlated with ER, PR, and HER2 expression. The role of estrogen and ER in the regulation of these three genes was assessed in several ER-positive and ER-negative breast cancer cell lines. RESULTS: In primary breast tumors, HOXB13 expression correlated negatively, and IL17BR and CHDH expression correlated positively, with ER status, and all three genes exhibited an ER-dependent correlation pattern with HER2 status that differs from PR and PS2, two canonical estrogen-regulated genes. Results using breast cancer cell lines show that these genes are regulated by estradiol in an ER-dependent manner, and that this regulation is abrogated by tamoxifen. CONCLUSIONS: HOXB13, IL17BR, and CHDH are estrogen-regulated genes, but their pattern of correlation with known positive (ER, PR) and negative (HER2) predictors of tamoxifen response differs from canonical ER signature genes. These results provide a biological rationale for the prognostic utility of these three genes in early-stage ER-positive breast cancer and for their potential to predict anti-estrogen resistance.     

Immunohistochemistry Subtypes (ER/PR/HER) of Breast Cancer: Where Do We Stand in the West of Saudi Arabia?

In Saudi Arabia, cancer of breast is ranked the most frequent neoplasm and second source of cancer deathin the female population. Breast cancer (BC) fast diagnosis, prognosis and medication management necessitate,these days, immunohistochemistry (IHC) assessment of hormone receptors and HER2 expression profile. Thepresent report defines the IHC profile of ER, PR and HER2 in Saudi female breast neoplasms of ductal andlobular types and associations ER, PR and HER2 expression patterns with various clinicopathological factors(age, type of tumor, size, laterality, histological grade, and involvement of axillaries lymph nodes). Ninety ninecases of breast tumors were recruited from the pathology department archive of King Abdulaziz UniversityHospital, Kingdom of Saudi Arabia. ER, PR and HER2 expression was assessed using IHC staining. Ductalcarcinomas with a variety of histological grades constituted 88 (88.8%) of total cases. Seventy four (77.8%), 59(62.1%), and 35 (36.8%) of ductal carcinomas showed positive staining for ER, PR and HER2, in that order.Remaining breast cancer cases were four (4%) lobular carcinomas and two (2%) mixed form of ductal andlobular types, which were ER+, PR+, and HER2-. Breast cancer expression pattern of ER, PR and HER2 inSaudi female is different from that of Tunisian and Jordanian female populations and closer to the expressionpattern of Egyptian, Lebanese, Iraqi and western country females. Furthermore, the present study found twoIHC patterns of breast cancer ER+/PR-/HER2+ (5%) and ER+/PR-/HER2- (11.1%), which had not been reportedin other Arabic studies. Thus the rates of IHC expression patterns in breast cancer show some variation amongArabic female populations.     

The Case to Case Comparison of Hormone Receptors and HER2 Status between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis

Background: Nowadays, the adjuvant treatment for breast cancer patients chosen depends on immunohistochemical pattern of Estrogen receptor(ER), Progesterone receptor(PR) and HER2 status of primary breast tumor. Several retrospective studies showed significant discordance in receptor expression between primary and metastatic tumors. The objective of this research was to determine discordant rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis of individual breast cancer patients in Thammasat University Hospital. Methods: A prospective observational study of all breast cancer patients who have axillary metastasis and underwent surgery at Thammasat Hospital between January 2011 to December 2015. Tumor staging, ER, PR, and HER2 status on primary breast tumor were recorded. Synchronous axillary lymph node metastasis was evaluated with immunohistochemistry for ER, PR, and HER2. Results: The ER-positive rate from primary tumor to synchronous axillary lymph node metastasis decreased from 74.7% to 71.7%; the HER2 overexpression rate was decreased from 26% to 24%. In contrast, PR positive rate were 71% in both primary tumor and synchronous axillary lymph node metastasis. In case to case comparison, discordance rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis were 11.1%, 20.2% and 10.1%, respectively. Furthermore, the tumor staging was not significant associated with discordance of ER, PR and HER2. Conclusion: ER, PR and HER 2 biomarkers showed significant concordance between primary tumor and synchronous axillary lymph node metastasis. Hence, if we cannot assess the ER, PR and HER2 status in primary tumor, then synchronous axillary lymph node metastasis can be studied instead. However, the repeat of biomarker testing in node-positive breast cancer patients may be beneficial for tailored adjuvant therapy, especially for patients with negative hormone receptor and/or HER2 profile on primary tumor.     

HER3在乳腺癌中的表达及临床意义

目的探讨乳腺癌患者HER3与HER2、ER和PR之间的关系及其对乳腺癌预后的影响。方法采用免疫组织化学SP法检测癌组织中HER3、HER2、ER和PR蛋白的表达,对患者随访,随访终点为总生存时间(overall survival,OS)。结果 HER2、HER3、ER和PR在136例乳腺癌患者中的阳性表达率分别为:50%、41.18%、60.9%和27.21%。HER3与年龄、淋巴结转移、分期、肿瘤类型以及化疗状态的差异无统计学意义(P>0.05)。HER3阳性与阴性患者OS差异有统计学意义(P=0.015)。HER3(+)HER2(+)组乳腺癌患者较其他组OS明显缩短(P=0.047)。HER3的表达与PR表达无明显关系(P=0.214),但可抑制ER产生(P=0.001)。HER2阳性和HER3的过度表达高度相关(P=0.000)。结论HER3可作为独立的临床预后因子,HER3阴性患者OS较长。     

RACK1: A superior independent predictor for poor clinical outcome in breast cancer

We aimed to investigate the expression of RACK1 in breast cancer, evaluate its role in predicting prognosis and compare with commonly used biomarkers: Ki67, ER, PR and HER‐2 for patients with breast cancer. The RACK1 expression and its clinical significance were examined in 160 breast carcinoma patients using immunohistochemistry. Correlations of RACK1 expression with other commonly used biomarkers and survival analyses were assessed. Immunohistochemistry results showed that the number of RACK1 cases scoring 0, 1, and 2 were 66, 54, and 40, respectively. RACK1 staining was strongly related to clinical stage, histological grade, Ki67, ER, PR and HER‐2 (all p < 0.05). Consistently, all of the cases exhibiting RACK1 staining score 0 were survivors, whereas the majority (55.0%) of those exhibiting RACK1 staining score 2 were deaths. Kaplan‐Meier survival analysis of 160 cases revealed a correlation between higher RACK1 expression levels and shorter overall survival times (p < 0.001). Univariate and multivariate analyses revealed that RACK1, tumor size, lymph node metastasis, and HER‐2 were independent prognostic factors (all p < 0.05). Interestingly, receiver operator characteristic (ROC) curves showed that the ROC areas for RACK1, Ki67, ER, PR and HER‐2 were 0.833, 0.766, 0.446, 0.387, and 0.689, respectively, and the superiority of RACK1 in sensitivity and specificity as biomarker was demonstrated. To our knowledge, it is the first time to investigate the expression of RACK1, and identified that RACK1 is a superior independent biomarker for diagnosis and prognosis comparing with currently widely used diagnostic index in breast carcinoma.     

乳腺浸润性导管癌预后相关因素分析

目的:探讨乳腺浸润性导管癌预后相关因素.方法: 收集130例乳腺浸润性导管癌资料,回顾性分析其临床特征、病理分化程度、复发转移情况、激素受体状况、人类表皮生长因子受体2的表达、临床治疗及生存情况.结果: c-erbB-2表达在ER、PR阳性组低于ER、PR阴性组(P<0.01),ER表达在PR阳性组高于PR阴性组(P<0.01);中、低分化与高分化相比,在淋巴结的转移、肿瘤的转移或复发、临床分期、肿块的大小上,均有统计学差异(P<0.05);单因素分析结果显示,激素受体状况、人类表皮生长因子受体2表达、病理分化程度、淋巴结状况、肿瘤转移或复发、临床分期、肿瘤大小、T分期、N分期、辅助化疗等11个因素与预后相关;多因素分析结果显示:ER状况、病理分化程度、淋巴结状况、临床分期是乳腺浸润性导管癌患者预后的独立影响因素.结论: 对乳腺浸润性导管癌,早期发现并针对病理分化程度及激素受体水平的适当治疗是提高生存期的关键.     

抑癌基因RASSF1A与乳腺癌发生发展关系的研究

目的 探讨RASSF1A基因在乳腺癌组织中的表达及其对乳腺癌发生发展的作用。方法 采用逆转录-聚合酶链反应(RT-PCR)方法检测51例乳腺癌组织、30例癌旁正常组织、12例乳腺良性肿瘤组织中RASSF1A基因mRNA的表达情况。结果 (1)RASSF1A mRNA在癌旁正常组织、良性肿瘤组织中均有表达,其表达量分别为0.463 03±0.150 69、0.480 64±0.135 69,二者之间的表达无明显差别(P＞0.05)。而该基因在乳腺癌组织中的表达缺失率为51.0%(26/51),其表达量为0.095 50±0.135 69,明显低于癌旁正常组织、良性肿瘤组织(P＜0.01);(2)乳腺癌组织中RASSF1A mRNA的表达低下或缺失与淋巴结转移相关(P＜0.05);(3)RASSF1A mRNA的表达低下或缺失与年龄、肿瘤大小、病理分型、组织学分级、激素受体和HER-2表达情况无显著相关(P＞0.05)。结论 RASSF1A基因表达缺失可能在乳腺癌的发生和发展过程中起重要作用,并影响其预后。     

乳腺浸润性导管癌预后相关因素分析

目的：探讨乳腺浸润性导管癌预后相关因素。方法：收集130例乳腺浸润性导管癌资料,回顾性分析其临床特征、病理分化程度、复发转移情况、激素受体状况、人类表皮生长因子受体2的表达、临床治疗及生存情况。结果：c—erbB-2表达在ER、PR阳性组低于ER、PR阴性组（P〈0．01）,ER表达在PR阳性组高于PR阴性组（P〈0．01）;中、低分化与高分化相比,在淋巴结的转移、肿瘤的转移或复发、临床分期、肿块的大小上,均有统计学差异（P〈0．05）;单因素分析结果显示,激素受体状况、人类表皮生长因子受体2表达、病理分化程度、淋巴结状况、肿瘤转移或复发、临床分期、肿瘤大小、T分期、N分期、辅助化疗等11个因素与预后相关;多因素分析结果显示：ER状况、病理分化程度、淋巴结状况、临床分期是乳腺浸润性导管癌患者预后的独立影响因素。结论：对乳腺浸润性导管癌,早期发现并针对病理分化程度及激素受体水平的适当治疗是提高生存期的关键。     

HER2 status in hormone receptor positive premenopausal primary breast cancer adds prognostic, but not tamoxifen treatment predictive, information

BACKGROUND: Overexpression of human epidermal growth factor receptor 2 (HER2) or amplification of its gene is a prognostic factor in primary breast cancer and a predictor for tamoxifen treatment efficacy in oestrogen receptor (ER) positive disease. In the present study we explored a defined cohort of breast cancer patients included in a randomised trial in order to assess prognostic and tamoxifen treatment information yielded by HER2 status. METHODS: Premenopausal breast cancer patients with stage II tumours (n = 564) were included and allocated to 2 years of adjuvant tamoxifen treatment versus no adjuvant treatment. ER, progesterone receptor (PR) status and HER2 status was determined by immunohistochemistry using a tissue microarray. HER2 amplification was analysed by fluorescent in situ hybridisation and tumours being amplified and/or HER2 3+ were considered HER2+. HER2 status was evaluable in 83% of the patients and 12.6% were HER2+. In untreated patients, HER2 was a negative prognostic factor in ER+ patients, HR 2.95; 95% CI: 1.61-5.38, p < 0.001, but not in ER- patients, HR 0.67; 95% CI: 0.28-1.61, p = 0.4, and a significant interaction between the two markers was found, p < 0.01. HER2 status was not related to tamoxifen treatment efficacy in ER+ patients (term of interaction p = 0.95). When stratifying for PR status, similar results were achieved. DISCUSSION: HER2+ and ER+ breast cancer constituted a subgroup of tumours with poor prognosis in premenopausal breast cancer, whereas no treatment interaction was found between HER2 status and tamoxifen in ER+ tumours. The poor prognosis in HER2+ and ER+ patients may interfere with the interpretation of HER2 data in non-randomised trials of adjuvant tamoxifen.