Safety Results of Docetaxel-(Taxotere(R))-Based Chemotherapy in Early Breast Cancer Patients of Asia-Pacific Region: Asia-Pacific Breast Initiative II / 한국유방암학회지

PURPOSE: The goal of this registry was to collect patient characteristics and safety data from patients from the Asia-Pacific region with early breast cancer receiving adjuvant chemotherapy containing docetaxel (Taxotere(R)). METHODS: This registry was open-label, international, longitudinal, multicenter, and observational in design and included a prospective group of consecutive early breast cancer patients with an intermediate-to-high risk of recurrence being treated with various docetaxel-based (anthracycline and non-anthracycline) adjuvant chemotherapy regimens during 2009-2013 in real-world clinical settings. RESULTS: The analysis included 1,712 patients, 79% of whom received docetaxel-based, anthracycline-containing regimens, while 21% received non-anthracycline-containing regimens. Patients receiving adjuvant docetaxel-based chemotherapy were followed for 1.5 years. Chemotherapy-related adverse events (AEs) were reported by 76.2% of patients (anthracycline-containing vs. non-anthracycline-containing regimens: 76.8% vs. 74.1%). Serious AEs were reported in 12% of patients (12.3% vs. 10%). National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or higher neutropenia was reported in 20% of patients (21.6% vs. 13.9%), leukopenia in 7.4% of patients (5.4% vs. 14.8%), and vomiting in 1.6% of patients (1.8% vs. 0.6%). Treatment-related death was reported in 27 patients (1.6%), while only 3% of patients had a relapse. Low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (HDL-C) and total cholesterol/HDL-C ratios increased after chemotherapy. A clinically insignificant reduction of 1.9% in left ventricular ejection fraction, from 66.43 to 64.53, was observed 1.5 years after therapy was completed. CONCLUSION: The Asia-Pacific Breast initiative II registry identified a variety of important facts regarding patient population characteristics, disease epidemiology and treatment response for early breast cancer patients of the Asia-Pacific region receiving docetaxel-based chemotherapy. Docetaxel-based chemotherapy did not show any significant safety concerns for early breast cancer patients of the Asia-Pacific region, and thus may represent a safe adjuvant chemotherapy regimen for these patients.

Safety and efficacy of first-line bevacizumab combined with taxane therapy in Chinese patients with HER2-negative locally recurrent or metastatic breast cancer: findings from the ATHENA study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.</p><p><b>METHODS</b>In the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.</p><p><b>RESULTS</b>Of 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.</p><p><b>CONCLUSIONS</b>We found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.</p>

A prospective comparison of molecular assay and touch imprint cytology for intraoperative evaluation of sentinel lymph nodes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastases enables the selection of patients for axillary lymph node dissections during the same operation, reducing the need for a second operation. The present study aimed to prospectively compare the GeneSearch(TM) Breast Lymph Node (BLN) Assay with touch imprint cytology (TIC) for intraoperative evaluation of SLNs.</p><p><b>METHODS</b>SLNs were sectioned in 1.5 - 3.0 mm pieces. TIC was performed on all pieces and the BLN Assay and postoperative histology evaluations were performed on different alternating node pieces. Overall performance of the BLN Assay was compared with that of TIC relative to the postoperative histology results.</p><p><b>RESULTS</b>A total of 90 patients enrolled in the study. Complete intraoperative data for both the BLN Assay and TIC were collected in 86 patients. The sensitivity, specificity, and overall accuracy of the BLN Assay were 82%, 97%, and 92%, respectively on a per patient basis compared with those of TIC which were 67%, 100%, and 90%.</p><p><b>CONCLUSIONS</b>Performance of the BLN Assay was superior to that of TIC and the additional application of TIC did not help improve the total sensitivity and accuracy of the intraoperative assessment. The existence of ectopic breast tissue might be a possible cause of false positive for the BLN assay. In addition, the BLN Assay complements histopathology assessment and can minimize sampling error without increasing pathologists' workload.</p>

Risk factors for postoperative seromas in Chinese breast cancer patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Seroma formation is one of the most common complications after breast cancer surgery. Various risk factors have been evaluated for their associations with the development of seromas in Western populations. However, similar data are not available in Chinese series. Therefore, we sought to investigate the potential risk factors for Chinese breast cancer patients.</p><p><b>METHODS</b>A prospective study of female breast cancer patients undergoing surgery was carried out in Cancer Hospital of Fudan University, Shanghai, China. Univariate analyses were performed by chi-square test or Student's t test or Mann-Whitney test and multivariate analyses by stepwise Logistic regression. The logistic model included age (years), total serum protein concentration (g/L), drainage volume on postoperative day 3 (POD 3; ml) and time to daily drainage volume not more than 30 ml (TTV30; days).</p><p><b>RESULTS</b>A total of 158 patients with breast cancer were studied. The mean age at diagnosis was (52.14 ± 10.77) years (range 25 - 92). During the follow-up period, 24 (15.2%) patients developed seromas. Calculated as continuous variables in the stepwise Logistic regression, age (OR = 1.090, 95%CI 1.028 - 1.155, P = 0.004), total serum protein concentration (OR = 0.886, 95%CI 0.791 - 0.992, P = 0.036), drainage volume on POD3 (OR = 1.013, 95%CI 1.002 - 1.023, P = 0.017) and TTV30 (OR = 1.273, 95%CI 1.039 - 1.561, P = 0.020) were independent risk factors for seroma formation. Additionally, significant difference in daily drainage volume was substantiated in the analysis by seroma formation (P = 0.034) rather than by type of surgery (P = 0.713).</p><p><b>CONCLUSIONS</b>Although the pathogenesis of seroma remains controversial, such risk factors as age, nutritional status, drainage volume on POD3 and TTV30 should be considered for prediction and prevention of seroma formation in Chinese breast cancer patients.</p>

Study on predictors of long term results for neo-adjuvant chemotherapy in locally advanced breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To identify predictive markers of the long-term outcome for neo-adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with intravenous vinorelbine (V) and epirubicin (E) combination regimen.</p><p><b>METHODS</b>One hundred and nineteen patients with LABC were treated from September 2001 to May 2006. All patients were diagnosed as invasive breast cancer by 14G core needle biopsy and treated with three cycles of VE regimen before the operation. The patients were subjected to surgery and subsequently were given other three cycles of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the clinical responses. Local-regional radiotherapy was applied to all patients after the chemotherapy and followed by hormone-therapy according to hormone receptor status. The impact of clinical, pathological, and immunohistochemical features on disease free survival (DFS) and overall survival (OS) was evaluated.</p><p><b>RESULTS</b>All patients were evaluable for responses: clinical complete response was documented in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response. The pathological complete response was found in 22 cases (18.5%). Of the patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%, respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67 expression (P=0.045), no pathological complete response after NC (P=0.034) were associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological complete response after NC (P=0.034) were associated with a shorter survival.</p><p><b>CONCLUSION</b>Pathological response in primary tumor, pre-Ki-67 and post-Ki-67 expression, pre-ER expression are important predictors of long-term outcome for LABC patients with three cycles of VE regimen before operation.</p>

Expression of CK5/6 and CK17 and its correlation with prognosis of triple-negative breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation of CK5/6 and CK17 expression with clinical outcome in patients with triple-negative [ER(-), PR(-), Her-2(-)] breast cancer.</p><p><b>METHODS</b>112 patients with breast cancer treated by surgery between 2000 and 2002 were included in this study. All cases were immunohistochemically proven to be triple-negative. Samples of formalin-fixed and paraffin-embedded surgical specimens were obtained for immunohistological examination for CK5/6 and CK17 expression. The correlation of the gene expression with clinicopathological features and outcome of the patients was analyzed.</p><p><b>RESULTS</b>Of the 112 triple-negative patients, five-year disease-free survival rate was 73.2% (82/112). The positive rate of both CK5/6 and CK17 was 21.4% (24/112), either CK5/6 or CK17 positive was 46.4% (52/112). It was shown by Kaplan-Meier curve that positive CK5/6, CK17 or CKs (CK5/6 or CK17 positive) was correlated with poor five-year disease-free survival (P = 0.020, P = 0.032, P = 0.003); and positive staining of CK5/6 or CKs was correlated with poor five-year overall survival (P = 0.027, P = 0.015). Of the 91 patients with invasive ductal carcinoma, a correlation of CK5/6 or CK17 positive staining with high grade differentiation was observed (P = 0.030), and with axillary lymph node metastasis was also noticed (P = 0.044). Multivariate analysis by Cox regression showed that differentiation grade, pathological stage and expression of CK5/6 were factors affecting both the disease-free-survival and overall-survival, while menopausal status was an independent factor affecting the disease-free-survival.</p><p><b>CONCLUSION</b>Positive expression of CK5/6 or CK17 in patients with triple-negative breast cancer is correlated with poor prognosis, high grade differentiation and axillary lymph node metastasis.</p>

A retrospective study of 129 cases with immediate breast reconstruction after skin-sparing mastectomy for breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the oncologic safety, indications and aesthetic results for skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR).</p><p><b>METHOD</b>One hundred and twenty-nine breast cancer patients treated by SSM + IBR from October 1999 to May 2007 were reviewed. Reconstructive techniques included latissimus dorsi flaps (38 patients), implants only (2 patients), latissimus dorsi flaps plus implants (61 patients), pedicled transverse rectus abdominis myocutaneous (TRAM) flaps (25 patients) and deep inferior epigastric artery perforator (DIEP) flaps (3 patients). Aesthetic results were judged by patients' self-evaluation.</p><p><b>RESULTS</b>Mean duration of hospitalization was 18.6 days. Time of first chemotherapy was 5.2 days after operation. Eleven patients (11/63, 17.5%) developed capsular contracture and 24 patients (24/99, 24.2%) developed seroma in the donor site. Nine patients (9/28, 32.1%) developed partial fat necrosis in TRAM and DIEP flaps. The satisfaction with the aesthetic results of the reconstructive breast was significantly lower in irradiated patients than non-irradiated ones. Median follow-up time was 11 months. Five patients developed local recurrence and 7 patients with metastasis.</p><p><b>CONCLUSIONS</b>SSM with IBR can be used for the 0 to II a stage breast cancer patients, with surgical oncologic and aesthetic satisfaction. Radiotherapy has an adverse effect on the reconstructive breast. Delayed or delayed-immediate reconstructions are recommended for patients indicated to postoperative radiotherapy.</p>

Surgical management of early breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the available surgical treatment modalities so as to explore the optimal strategy of managing early breast cancer.</p><p><b>METHODS</b>The clinical data of 2173 consecutive early-stage breast cancer patients treated by surgery treatments were retrospectively reviewed in order to clarify the indications and contraindications of different modalities. Therapeutic outcome of different surgical treatment modes were compared in terms of recurrence-free survival ( RFS) , disease-free survival ( DFS) , overall survival (OS). The cosmetic results of breast conservation and reconstruction were also evaluated .</p><p><b>RESULTS</b>The median age of these patients was 51 years ranging from 18 to 91. Of 2173 patients, 547 had stage 0- I lesions and 1626 stage II , and 1155 (53. 2% ) premenopausal. The proportion of patients who received radical surgery, breast conservation and reconstruction after mastectomy was 83. 6% (1817/2173), 10. 5% (229/2173) and 2. 5% (55/2173) , respectively. Younger and premenopausal patients prefer conservative and reconstructive surgeries, which are reasonable for stage 0-I and non-invasive breast cancer patients. Conservative surgery was not suitable for Paget's disease of breast (P = 0. 004) , mastectomy followed by reconstruction in this type of cancer was up to 38. 5%. The recurrence and metastasis rate of conservation or mastectomy were similar with a comparable 3-year RFS of 97. 4% and 95. 4% , respectively; there were also no significant differences in RFS(P =0. 2435) , DFS( P =0. 1395) and OS(P =0. 9406) after having been followed for 3 to 64 months. Similarly, immediate reconstruction did not show any negative effects with only 1 recurrence and 1 metastasis. Aesthetic outcomes were assessed as excellent or good in 90. 0% of breast conservation surgery, and the acceptability of reconstruction was 94. 5%.</p><p><b>CONCLUSION</b>Breast conserving surgery not only has comparable survival as mastectomy, but also has better cosmetic outcomes. Immediate breast reconstruction can be a suitable option without compromising survival. It is very important in the management for early breast cancer by selecting the most suitable surgery mode for every individual patient not only to cure her disease but also to satisfy the patient psychologically. Conservation should be preferred prior to reconstruction whenever possible.</p>

5589del8: the recurrent mutation of BRCA1 gene in Chinese breast cancer patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the "hot spot" of BRCA1/2 gene mutations in Chinese mainland breast cancer population.</p><p><b>METHODS</b>The known BRCA1/2 gene mutations in author's previous studies were reanalyzed by denaturing high performance liquid chromatography and DNA sequencing method in 177 patients with early onset breast cancer or affected relatives and 426 sporadic breast cancer patients from four breast cancer centers in China.</p><p><b>RESULTS</b>Three cases were found with BRCA1 5589del8 mutation out of 247 hereditary-predisposing breast cancer patients (70 patients in previous study and 177 patients in current study) and 2 cases with BRCA1 5589del8 mutation out of 426 sporadic breast cancer patients. They had similar even same haplotype.</p><p><b>CONCLUSION</b>BRCA1 5589del8 mutation is likely to be the "founder mutation" in Chinese population, but it should be confirmed by further studies.</p>

BRCA1 germ line mutations in Chinese early-onset breast cancer patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the role of disease associated germ line mutations in BRCA1 gene among Chinese early-onset breast cancer patients.</p><p><b>METHODS</b>A total of 188 early-onset breast cancer patients, who were diagnosed with breast cancer before 41-year-old, were enrolled from four breast cancer clinical centers in China. Thirty-nine of them (20.7%) also had family history of breast/ovarian cancer. DNA extracted from lymphocytes was amplified by polymerase chain reaction (PCR) for the entire exons and the splicing sites of BRCA1. Twenty-two of the patients were screened by single strand conformation polymorphism (SSCP), and the other 166 of them were screened by denaturing high performance liquid chromatography (DHPLC). The abnormal fragments recognized were ascertained by DNA direct sequencing. For those samples with the same recurrent mutation, five BRCA1-linked markers (D17S855, D17S1322, D17S1323, D17S1326 and D17S1327) were used for the allelotype analysis.</p><p><b>RESULTS</b>Twelve disease-associated mutations were identified in 15 (8.0%) patients, among which BRCA1 1100delAT and 5589del8 were identified in 3 and 2 patients respectively. Nine (23.1%) of them were identified in those with breast/ovarian cancer family history. The difference of BRCA1 mutation frequency between the patients with and without family history was statistically significant (P=0.001). Allelotype analysis showed the two BRCA1 5589del8 mutation carriers shared the same allelotype in all the 5 STR sites, and two of the three 1100delAT mutation carriers, who came from the northern China, also shared the same allelotype in all the 5 STR sites, which were different from those of the 5589del8 mutation carriers'.</p><p><b>CONCLUSION</b>This is a relatively very large scale multi-hospital-based study of BRCA1 mutations in Chinese early-onset breast cancer patients up to now. It seems reasonable to give genetic consultations and genetic test of BRCA1 gene to early-onset breast cancer patients in China, especially for those with breast/ovarian cancer family history. The two recurrent mutations might be founder mutations of Chinese population. It might be cost-effective to analyze these two mutations before whole gene analysis.</p>

Prevalence of Val158Met polymorphism in COMT gene on non-BRCA1/2 hereditary breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the prevalence of Val158Met polymorphism in Catechol-O-methyltransferase (COMT) gene and its effect on genetic susceptibility for breast cancer in Shanghai population.</p><p><b>METHODS</b>A total of 114 patients with BRCA1/BRCA 2 negative hereditary breast cancer from independent families and 121 age-matched healthy controls were analyzed. Genotype analysis was conducted by polymerase chain reaction (PCR) and then DNA direct sequencing. The odd ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression model.</p><p><b>RESULTS</b>The frequency of Val158Met polymorphism GG, GA and AA genotype in case group and control was 0.58 (65), 0.32 (36), 0.10 (11) and 0.60 (66), 0.35 (41), 0.03 (3), respectively. The frequency of allele-containing genotypes is significantly higher in early-onset breast cancer patients (0.57) than in familial ones (0.35). Compared with GG (Val/Val) genotype, AA (Met/Met) genotype confers a significantly increased risk for breast cancer (adjusted OR = 3.15; 95% CI, 0.70 - 14.19), especially among premenopausal women (adjusted OR = 9.98; 95% CI, 1.00 - 99.64). Borderline significantly association was found between AA genotype (adjusted OR = 7.57; 95% CI, 0.57 - 101.28) and susceptibility for breast cancer in BMI < or = 23 kg/m(2) group.</p><p><b>CONCLUSIONS</b>Val158Met polymorphism in COMT gene could be a candidate for low penetrance breast cancer susceptibility in Shanghai population, especially among premenopausal women and early-onset breast cancer patients.</p>

Stereotactic biopsy for non-palpable breast lesions: evaluation and choice of minimal invasive and excisional biopsy / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate three biopsy methods which are currently used in stereotactic breast biopsy.</p><p><b>METHODS</b>A total of 361 cases of stereotactic breast biopsies were carried out since 2000, including 73 cases of true cut core needle biopsies (ST-CNB), 74 cases of vacuum assisted biopsies (ST-VAB) and 214 cases of excisional biopsies. After medium follow-up time of 18 months (6 to 66 months), the accuracy as well as the clinical benefits of the three stereotactic biopsy procedures were analyzed retrospectively.</p><p><b>RESULTS</b>The cancer miss rate of stereotactic wire localized excisional biopsy, ST-CNB and ST-VAB is 0, 2.7% and 0 respectively. Under-estimate rate of minimal invasive biopsy was 33% in atypical ductal hyperplasia (ADH) and 53% in ductal carcinoma in situ (DCIS). The minimal invasive procedure is superior to surgical procedure in terms of operation time, breast cosmetic outcome and complications, etc. Furthermore, 69% of the surgeries for suspicious lesion were waived.</p><p><b>CONCLUSIONS</b>Stereotactic minimal invasive breast biopsy, especially ST-VAB, is an accurate, safty and convenient diagnosis technique and could be considered as the first line choice for mammographic moderate suspicious breast lesions (BIRADS-4). However, further excisional biopsy is recommended for atypical hyperplasia. Stereotactic excisional biopsy could be directly used for diagnosis of mammographic highly suspicious breast lesions (BIRADS-5).</p>

A study of the combination of vinorelbine and epirubicin as neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and toxicity of vinorelbine (N) and epirubicin (E) as the neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer (LABC).</p><p><b>METHODS</b>From September 2001 to December 2004, 158 patients with LABC were treated with NE chemotherapy before operation. Neoadjuvant chemotherapy containing vinorelbine (N), 25 mg/m(2) (days 1 and 8) and epirubicin (E), 60 mg/m(2) (days 1) was administered every 3 weeks for three cycles before local treatment.</p><p><b>RESULTS</b>Response in the breast: the clinical objective response was 81.6% [23.4% (37/158) cCR and 58.2% (92/158) PR], 16.5% (26/158) SD and 1.9% (3/158) PD. Pathological complete response was found in 29 cases (18.3%). Eighteen cases (26.5%) who have positive FNA result in the axillary lymphnode before chemotherapy showed negative result in the surgery specimen. The most common toxicities were neutropenia, alopecia and nausea/vomiting. Neutropenia grade 3 - 4 was reported in 111 patients (70.3%) and there was no toxic deaths.</p><p><b>CONCLUSIONS</b>The combination of vinorelbine and epirubicin is a very active and well-tolerated regimen as neoadjuvant chemotherapy for the LABC.</p>

Biological significance of E-cadherin in an inflammatory breast carcinoma cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects of E-cadherin on the biologic behavior of SUM149, an inflammatory breast cancer cell line.</p><p><b>METHODS</b>SUM149 cells were transfected with dominant-negative mutant E-cadherin expressing plasmid. The positive clones with higher expression of dominant-negative E-cadherin mutant were identified by RT-PCR and fluorescent flow cytometry method. The differences in cell growth, proliferation and invasion between positive clones and controls were compared.</p><p><b>RESULTS</b>Whereas the proliferation of positive clones was of no change, compared with controls, the ability of invasion was decreased and the mRNA levels of MMP-1 and MMP-9 were downregulated. Gelatin zymography analysis also confirmed the decreasing expression of MMP-9 in the positive clones.</p><p><b>CONCLUSION</b>In this cell line model, down-regulation of E-cadherin can inhibit the ability of invasion of this inflammatory breast cancer cell line.</p>

Expression of ER alpha in chemically induced MDA-MB-435 cells and its responsiveness to endocrine / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of ER alpha in chemically induced, ER alpha-negative human breast cancer MDA-MB-435 cells and its restoration of the responsiveness to endocrine therapy.</p><p><b>METHODS</b>MDA-MB-435 cells were treated with HDAC inhibitor trichostatin A(TSA)and DNMT1 inhibitor 5-AZA-CdR (AZA). The mRNA level of ER alpha, PR and PS2 in treated MDA-MB-435 cells was detected by RT-PCR. The WST-8 (water-soluble tetrazolium salt-8) method was used to analyze the proliferation rate of the cells. Xenograft in female nude mice was used to further explore the change of proliferation rate of treated MDA-MB-435 cells in vivo.</p><p><b>RESULTS</b>After treatment with AZA and TSA, mRNA expression of ER alpha, PR and pS2 was up-regulated in MDA-MB-435 cells. The mRNA level of ER alpha was the hightest when MDA-MB-435 cells were treated with 2.5 micromol/L AZA and 100 ng/ml TSA. The treated MDA-MB-435 cells showed different proliferation rate in various media containing different concentration of estrodial. The MDA-MB-435 cells showed down-regulated proliferation rate after treatment with the combination of 2.5 micromol/L AZA and 100 ng/ml TSA, and 4-OH tamoxifen could suppress the growth rate of the induced MD-MBA-435 cells but not the untreated cells. The treated MDA-MB-435 cells showed slower proliferation rate than that of untreated cells in vivo (P <0. 01), and the proliferation rate of the treated MDA-MB-435 cells became lower when the nude mice were deprived of estrogen by castration (P <0. 01).</p><p><b>CONCLUSION</b>After treatment with TSA and AZA, ER alpha-negative MDA-MB-435 cells can express functional ER alpha and regain responsiveness to estrogen both in vitro and in vivo. HDAC inhibitor and DNMT1 inhibitor may play an important role in restoration of sensitivity of ER alpha-negative breast cancers to endocrine therapy.</p>

Downregulation of Duffy antigen receptor for chemokine (DARC) is associated with lymph node metastasis in human breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the relationship between Duffy antigen receptor for chemokines (DARC) and the metastasis potential in human breast cancer. METHODS Breast cancer tissue sections from 75 patients, grouped according to the local lymph node status were examined immunohistochemically for protein level of DARC. Microvessel density (MVD) was counted by endothelial cells immunostained using anti-CD34 antibody.</p><p><b>RESULTS</b>Strong positive DARC immunostaining in lymph node negative and positive groups was detected in 31 cases (81.6%) and 18 cases (48.6%), respectively (P < 0.01). MVD was (35.67 +/- 17.96)/HP and (53.38 +/- 20.29)/HP in DARC strong positive and less positive cases (P < 0.01). In those patients with lung, bone, hepatic distant metastasis (13 cases), 9 cases (69.2%) were DARC less positive, 4 cases (30.8%) were DARC strong positive. The correlation coefficient was -0.412 between DARC expression and MVD and the corresponding value was -0.346 between DARC expression and lymph node status and -0.333 between DARC expression and distant metastasis in breast cancer.</p><p><b>CONCLUSION</b>DARC may play a negative role in the process of neoangiogenesis, and probably has an association with the lymph node status.</p>

BRCA1 and BRCA2 gene mutations of familial breast cancer from Shanghai in China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of BRCA1 and BRCA2 gene mutations among breast cancer patients with affected relatives in Shanghai of China.</p><p><b>METHODS</b>Thirty-five breast cancer patients who had at least one first-degree relative affected were analyzed, among whom 13 patients suffered from breast cancer at age of less than 40 years. A comprehensive BRCA1 and BRCA2 mutation analysis was performed through denaturing high-performance liquid chromatography (DHPLC) and subsequent DNA direct sequencing.</p><p><b>RESULTS</b>Four mutations in BRCA1 gene, including 2 novel splice-site mutations (IVS17-1G>T, IVS21+1G>C) and 2 frameshift mutations (1100delAT; 5640delA) were identified. One frameshift mutation (5802delAATT) was detected in exon 11 of BRCA2. Additional 12 novel single nucleotide polymorphisms(SNPs) were detected, including a novel unclassified variant and 7 novel intronic variants in BRCA1, and 4 novel intronic variants in BRCA2, with which all caused no alteration of amino acid coding. The mutation frequency of BRCA1 and BRCA2 in patients with family history was 11.4% and 2.9%, respectively.</p><p><b>CONCLUSION</b>Two novel mutations in BRCA1 may be mutations characterized to familial breast cancer of Chinese Shanghai population. The BRCA2 may contribute to mutation less than BRCA1 in familial breast cancer. Our data contribute to information on mutation spectrum of BRCA gene in Chinese population and also offer a recommended screening mode for clinical genetic testing policy in China.</p>

Effect of R264C polymorphism in CYP19A1 gene on BRCA1/2-negative hereditary breast cancer from Shanghai population of China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Aromatase, encoded by CYP19A1, play an important role in estrogens biosynthesis from androgens. The present study is to investigate effect of R264C single nucleotide polymorphism in CYP19A1 gene on genetic susceptibility for hereditary breast cancer without BRCA1/2 mutant.</p><p><b>METHODS</b>One hundred and fourteen BRCA1/2 -negative hereditary breast cancer patients from independent families and 121 age-matched healthy control subjects were analyzed. Genotype analysis was performed through polymerase chain reaction (PCR) and then DNA direct sequencing. The odd-ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional Logistic regression model.</p><p><b>RESULTS</b>The frequency of R264C single nucleotide polymorphism CC, CT and TT genotype in case group and controls was 84(77.8%), 22(20.4%), 2(1.8%) and 87(77.7%), 24(21.4%), 1(0.9%), respectively. CT genotype (OR=1.16, 95%CI: 0.53-2.55) and TT genotype (OR=1.44, 95%CI: 0.12-17.15) did not confer a significantly increased risk for breast cancer. No significant association was found between T allele and susceptibility for breast cancer under analysis according to menopausal status and body mass index.</p><p><b>CONCLUSION</b>R264C polymorphism in CYP19A1 gene is not a candidate locus for low penetrance breast cancer susceptibility in Shanghai group of Chinese population and not recommended in clinical genetic test. Homozygous T allele of R264C is not common in Shanghai group of Chinese population.</p>

CHEK2 c.1100delC may not contribute to genetic background of hereditary breast cancer from Shanghai of China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of CHEK2 c.1100delC mutation among non-BRCA1/BRCA2 familial/early-onset breast cancer patients in Shanghai.</p><p><b>METHODS</b>One hundred and fourteen non-BRCA1/BRCA2 hereditary breast cancer patients were analyzed, among whom 76 cases had at least one first-degree relative affected with breast cancer and 38 cases were diagnosed as breast cancer below the age of 40 years without family history. The mutation genotyping of CHEK2 c.1100delC were carried out through long-range PCR amplifying of exons 10-14, and followed by amplification of exon 10 and then DNA direct sequencing.</p><p><b>RESULTS</b>No c.1100delC frame-shift mutation was identified in our studied population. One novel missense mutation 1111C>T (p.His371Tyr), located in kinase catalytic domain, was found in 3 familial breast cancer cases but no one in control group.</p><p><b>CONCLUSION</b>CHEK2 c.1100delC is rare variant for Chinese population and may not contribute to predisposition for hereditary breast cancer in Shanghai. Novel variant -1111C>T could be in association with genetic susceptibility to breast cancer. A further study is needed to confirm the results.</p>

Value of magnetic resonance imaging in diagnosing breast lesions which need biopsy / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate MRI in diagnosing breast lesions which need biopsy.</p><p><b>METHODS</b>One hundred and eight patients were admitted to hospital for biopsies due to one hundred and sixteen suspicious lesions detected in their breasts. These lesions were detected by physical examination, mammography or ultrasonography. They were also administrated MRI examination before biopsy. The sensitivity and specificity of each diagnostic method were obtained and the radiologic-pathologic correlation was meanwhile calculated.</p><p><b>RESULTS</b>Seventy (60.3%) breast lesions were diagnosed malignancy. The sensitivity, specificity, accuracy, positive prognostic value and negative prognostic value of ultrasonography were 83.3%, 62.0%, 74.1%, 74.3% and 73.8%. Such data of mammography were 86.8%, 68.1%, 78.0%, 75.4% and 82.1%. And those of MRI were 97.1%, 73.9%, 87.9%, 85.0% and 94.4%.</p><p><b>CONCLUSION</b>MRI is superior to ultrasonography and mammography in diagnosing breast lesions, especially for the nonpalpable lesions.</p>