Feng Xi Su

The prevalence of BRCA1 and BRCA2 germline mutations in high-risk breast cancer patients of Chinese Han nationality : two recurrent mutations were identified

To have an overview of the role of BRCA1 and BRCA2 genes among Chinese high-risk breast cancer patients, we analyzed 489 such high-risk breast cancer patients from four breast disease clinical centers in China, by using PCR-DHPLC or SSCP-DNA sequencing analysis. Allelotype analysis was done at five short tandem repeat (STR) markers in or adjacent to BRCA1 on the recurrent mutation carriers. For those analyzed both genes, 8.7% of early-onset breast cancer cases and 12.9% of familial breast cancer cases had a BRCA1 or BRCA2 mutation, as compared with the 26.1% of cases with both early-onset breast cancer and affected relatives. For those reporting malignancy family history other than breast/ovarian cancer, the prevalence of BRCA1/2 mutation is about 20.5%, and it was significantly higher than the patients only with family history of breast/ovarian cancer (Pxa0=xa00.02). The family history of ovarian cancer (26.7% vs. 11.9%) and stomach cancer (23.8% vs. 11.8%) doubled the incidence of BRCA1/2, but the difference did not reach the statistical significance. Two recurrent mutations in BRCA1, 1100delAT and 5589del8, were identified. The recurrent mutations account for 34.8% BRCA1 mutations in our series. Similar allelotypes were detected in most STR status for those harboring the same mutations. The BRCA1 associated tumors were more likely to exhibit a high tumor grade, negative C-erbB-2/neu status and triple negative (ER, PgR and C-erbB-2/neu negative) status (Pxa0<xa00.05). We recommended the BRCA1 and BRCA2 genetic analysis could be done for high-risk breast cancer patient in Chinese population, especially for those with both early-onset breast cancer and affected relatives. There may be some degree of shared ancestry for the two recurrent BRCA1 mutations in Chinese.

A prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving patients' persistence to adjuvant aromatase inhibitor medication for postmenopausal, early stage breast cancer

Since the rate of persistence to adjuvant endocrine therapy such as 5-year aromatase inhibitors (AI) would decrease over time in patients with hormone-sensitive breast cancer, it is necessary to investigate if a patient support program could modify patients’ beliefs and improve their persistence to AI treatment. This was a prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving postmenopausal patients’ persistence to adjuvant AI medication for early stage breast cancer (NCT00769080). The primary objective was to compare the rates of 1-year persistence to upfront adjuvant AI for patients in the two observational arms (standard treatment group and standard treatment plus patient support program group). In this study, 262 patients were enrolled in the standard treatment group and 241 patients in the standard treatment plus patient support program group. The mean 1-year persistence rates were 95.9 and 95.8xa0% for the standard treatment group and the standard treatment plus patient support program group, respectively (Pxa0=xa00.95). The mean times to treatment discontinuation were 231.2xa0days in the standard treatment group and 227.8xa0days in the standard treatment plus patient support program group, with no statistically significant difference between the two groups (Pxa0=xa00.96). There was also no statistically significant difference in the reason for treatment discontinuation (Pxa0=xa00.32). There was a significant relationship between the patient centered care questionnaire and poor persistence (odds ratioxa0=xa03.9; 95xa0% CI, 1.1–13.7; Pxa0=xa00.035), suggesting that the persistence rate of patients with whom the doctor always or usually spends time is greater than that of patients with whom the doctor sometimes or never spends time. Patients’ persistence to adjuvant AI medication for postmenopausal, early stage breast cancer is relatively high in the first year and is not significantly increased by adding a patient support program to standard treatment.

Evaluating the performance of models for predicting the BRCA germline mutations in Han Chinese familial breast cancer patients

Purpose Established models (Penn, Myraid and BRCApro) are useful of estimating the probability that a person has a BRCA mutation. But the value of these models in Chinese population is unclear. The aim of the study is to evaluate the performance of three models on the assisting in pre-test genetic risk counseling. Methods Three risk assessment models, Penn II, Myriad and BRCApro, were applied to 212 familial breast cancer patients who had undergone BRCA1/2 mutation analysis. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operator characteristic (ROC) curve were calculated for each model. Results Myriad showed a better ROC curve than BRCApro either for BRCA1 or BRCA1/2 combination mutation prediction, but BRCApro had a higher positive likelihood ratio when using 10% as the probability threshold. The performance of three models improved when they were evaluated in 66 patients from high risk families, presenting increased ROC and positive likelihood ratio. Especially that of BRCApro for BRCA2, the ROC was increased to 0.716 and its positive likelihood was 5.6. Conclusion Three models had the similar impact on the pre-test probability of BRCA mutation. But at a 10% cutoff point, BRCApro had the best BRCA mutation carrier prediction value. The performance of BRCApro for BRCA2 mutation prediction was improved when it was restricted in patients from high risk families.

Models for predicting BRCA1 and BRCA2 mutations in Han Chinese familial breast and/or ovarian cancer patients

Purpose Our aim was to find an appropriate method to estimate the likelihood that a family history of cancer was a result of a mutation in the BRCA1 or BRCA2 genes. We also compared the performance of the established method with three different methods (Couch, Sh-E and BRCApro) to identify an alternative strategy for genetic council targeted to the specified population. Patients and methods The family history as well as individual information of two hundred unrelated probands who had completed BRCA1 and BRCA2 mutation screening was analyzed to assess the likelihood of a pathogenic mutation. A model was developed by empirical method. The performance of this model was validated in a separate patient cohort compared with BRCApro. Results Several factors were associated with mutations in univariate analysis and a logistic model was devised to estimate the probability for a proband of harboring a mutation in BRCA1 and/or BRCA2. Using a greater than 10% probability threshold, the highest accuracy was achieved by the established model when compared to other three models, presenting the highest sensitivity, PPV, NPV and area under ROC curve. The empirical model showed a better ROC curve compared to BRCApro in the verification cohort. Conclusion A probability model targeted to Han Chinese population should be a useful tool in the genetic counseling for the specified ethnic. Its ability to predict BRCA2 mutation carriers needs to be improved.

GeneSearch™ BLN Assay could replace frozen section and touch imprint cytology for intra-operative assessment of breast sentinel lymph nodes

BackgroundBreast cancer sentinel lymph node (SLN) biopsy has become a common procedure. The GeneSearch™ Breast Lymph Node Assay is a real-time reverse-transcriptase polymerase chain reaction assay for detecting nodal metastases larger than 0.2xa0mm. The trial is a prospective multi-center clinical trial conducted to validate the assay in China.MethodsFour hundred and seventy-nine consecutive prospective patients were enrolled from six centers. SLNs were sectioned along the short axis into multiple blocks. Odd blocks were tested by the assay intra-operatively, and even blocks were assessed by post-operative histology. Six 4- to 6-μm-thick sections were taken every 150xa0μm per block. In addition, intra-operative histological assessments were performed on the even blocks of 214 patients by frozen section (FS) and all blocks of 156 patients by touch imprint cytology (TIC).ResultsA total of 1046 SLNs were excised. Overall performance of the assay compared to post-operative histology was accuracy of 91.4xa0%, sensitivity of 87.5xa0%, and specificity of 92.9xa0%. There were no significant differences in assay performance of each center. After a learning curve of about 10 cases, the assay could be performed in a median time of about 35xa0min. The sensitivity of the assay was similar to the FS (84.9xa0%, Pxa0=xa00.885) and was significantly higher than the TIC (70.0xa0%, Pxa0=xa00.007) while the specificity of all were comparable.ConclusionThe GeneSearch™ Breast Lymph Node Assay is an accurate and rapid intra-operative assay for breast SLNs and it can replace FS and TIC for application.

Abstract P2-12-19: Comparison between ultrasound-guided-vacuum-assisted excision and surgical excision of benign phyllodes tumor of the breast: A single center retrospective study

Background: Wide local excision (WLE) is the recommended treatment for patients with phyllodes tumor of the breast, regardless of the tumor subtype (benign, borderline and malignant). However, the association between margin status and local recurrence is still controversial. In our institution, surgical excision (SE) alone (margin width Method: We searched our database for patients with benign phyllodes tumor diagnosed in Sun Yat-sen Memorial Hospital between 2000 and 2014, and identified 136 patients with valid follow-up information. Formalin fixed slices of each patient were reviewed for pathology diagnosis. In UGVAE group, we used 8G Mammotome to remove all lesions detected by ultrasound and surgical re-excision after pathology diagnosis was not performed. In SE group, patients received SE with no intention to achieve a surgical margin >=1cm. Macroscopically negative margins is guaranteed by gross examination. Comparison of patients9 features were performed using student t-test, Mann–Whitney u-test or Chi-sqaure test, when appropriate. Association between surgery (UGVAE & SE) and local recurrence was analyzed using univariate (Kaplan-Meier analysis) and multivariate approaches (Cox-regression analysis). Age, tumor size and the presence of accompanied fibroadenoma were included in the multivariate analysis. Results: Patients had significantly smaller tumor in the UGVAE group and those in the SE group (Median size: 2.1 vs. 3.0cm, P Conclusion: UGVAE alone did not significantly increase the local recurrence rate of benign phyllodes tumor, when compared with SE, in this study. A prospective study with more patients and longer follow-up is needed in future. Citation Format: Ouyang Q, Chen K, Zhu L, Song E, Su F. Comparison between ultrasound-guided-vacuum-assisted excision and surgical excision of benign phyllodes tumor of the breast: A single center retrospective study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-12-19.

Abstract P1-01-09: Which nomograms may be the best for predicting nonsentinel lymph node metastasis in breast cancer patients: a meta-analysis.

Background: Axillary lymph node dissection (ALND) is the standard treatment for breast cancer patients with positive sentinel lymph nodes (SLNs). Several nomograms were developed to identify SLN-positive patients with low risk of nonsentinel lymph nodes (NSLNs) metastasis. These nomograms were validated in different populations and it is still unknown which is the best. This study is to present a systemic review and perform a meta-analysis to obtained the pooled AUC (Area Under the receiver-operator Curve) value of each models. Methods: This review focused on six models: Cambridge, MSKCC, Mayo, MDA, Tenon and Stanford models. A “Pubmed” search and “Web of science” search were conducted and 35 literatures were ultimately included. AUC and the number of patients with positive NSLNs were extracted. Publication bias and heterogeneity were analyzed. AUCs were converted to odds ratios (ORs) for combination. The combined ORs were converted back to AUCs to represent the integrated discriminative capabilities of each models. Findings: In total, the Cambridge, Mayo, MDA, MSKCC, Stanford and Tenon models were validated in 8, 6, 4, 39, 14 and 15 studies, with 2156, 2431, 843, 8143, 3700 and 3648 patients included, respectively. There were no publication bias or heterogeneity observed in the Cambridge, Mayo, MDA and Tenon models (Table 1). The combined ORs and the corresponding AUCs of each models were listed as follow: Cambridge (OR = 3.86, AUC = 0.71), Mayo (OR = 3.71, AUC = 0.71), MSKCC (OR = 3.47, AUC = 0.70), MDA(OR = 3.44, AUC = 0.70), Tenon (OR = 3.46, AUC = 0.70) and Stanford (OR = 2.92, AUC = 0.67). For each of the predictive models, both fixed and random effect models were used to calculate the combined OR. The presence of larger difference between the fixed and random effect analysis suggests small study effects, rendering the meta-analysis relatively less reliable. The combined ORs were identical when fixed and random effect models were used in the Cambridge and MDA models, suggesting that there was no small study effects in these two models. Conclusions: All of the included models are all better than random chance but not provide excellent discriminative capabilities. The Cambridge and Stanford models were relatively superior and inferior when compared with the other models, respectively. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-09.

P3-07-13: Validation and Comparison of Models To Predict Nonsentinel Lymph Node Metastasis in Chinese Breast Cancer Patients with Positive Sentinel Lymph Nodes.

Background: Several models for predicting the risk of nonsentinel lymph node (NSLN) metastasis in breast cancer patients with positive sentinel lymph nodes (SLNs) have been developed. Independent validation of these models in different populations is necessary before clinical application. This study aimed to validate and compare these models in Chinese patients. Patients and Methods: A total of 159 breast cancer patients with positive SLNs treated at our institution were included. Chi-squared tests, RP-ROC, CART and multivariate logistic regression were used to analyze the risk factors for NSLN involvement in our population. ROC curves, calibration plots and false-negative (FN) rates were evaluated for 11 reported models. The threshold of each model for classifying patients into the low-risk group was adjusted to render the FN rate close to 10%. Results: In total, 81 (50.9%) patients had at least one NSLN involvement. Univariate and multivariate analyses revealed that the number of negative SLNs (P With adjusted thresholds, the Mayo model outperformed the others by classifying the highest proportion of patients (20%) into the low-risk group. The Cambridge, Mou and MDA models defined 17.0%, 14.5% and 15.1% of patients as low-risk, respectively. Conclusion: The Cambridge and Mou models performed well in Chinese patients. ROC curves, calibration plots and FN rates should be used together for the accurate evaluation of prediction models. The analysis of the clinicopathological features of the targeted population is critical for the selection of the most appropriate model. The models specifically designed for patients with micrometastases or macrometastases of SLNs are needed in the future. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-13.

China Validation Study of GeneSearchTM Breast Lymph Node Assay for the Diagnosis of Sentinel Lymph Nodes of Breast Cancer – CBCSG-001a Interim Results.

Background: The use of sentinel lymph node (SLN) biopsy is becoming the standard of care in China. With the adoption of this technique there is an increasing need for rapid and accurate detection of metastases in the SLNs. Histological intra-operative techniques such as touch imprint and frozen section offer limited sensitivity, increasing the risk of intra-operatively missing relevant SLN metastases (>0.2 mm). Post-operative histology (HE69(24 Suppl):Abstract nr 1023.