BACKGROUD: Women with unilateral breast cancer are at increased risk for developing contralateral disease. The objective of the single-center retrospective study was to evaluate the incidence of bilateral breast cancer (BBC) and to analyze the clinicopathological characteristics for BBC in China. METHODS: We retrospectively reviewed the electronic medical records of 3924 female patients with breast cancer consecutively treated at the department of Breast Oncology in the Peking University Cancer Hospital between 2006 and 2016. BBC was categorized as synchronous (within 6 months) or metachronous bilateral breast cancer (after 6 months of a first tumor). Patients with BBC were identified according to the criteria described by Chaudary et al. Patients with stage IV first breast cancer, and those who were found to have distant metastases between the first and second primary breast cancer were excluded. Analyses of demographic, clinicopathologic, and treatment characteristics were done between sBBC and mBBC. RESULTS: The incidence of BBC in our population was 3.2% (127 of 3924). Of those, 2.5 % ( 99 of 3924) were metachronous bilateral breast cancer ( mBBC ), and 0.71 % (28 of 3924) were synchronous bilateral breast cancer ( sBBC ). The overall median age of the patients at first diagnosis was 45 years (range, 27-81 years). The age of onset of the first mBBC was significantly younger than that of sBBC ( p = 0.027). In mBBC subgroups, the median time interval between first and second tumors was 68 months (range, 7-342 months), and 80.8% of the second tumor were diagnosed within 10 years of the diagnosis of the first tumor. A positive family history of breast cancer was found in 25% of sBBC and 9.1% of mBBC ( p = 0.025). In ER-negative first tumor of mBBC, 56.1% of the second tumor were ER-positive. Mastectomy was the commonest surgery performed in these patients. CONCLUSIONS: Our results confirmed the necessity of screening contralateral breast at the diagnosis of unilateral breast cancer and following-up for Chinese patients with breast cancer. Citation Format: Li H, Jiang H, Zhang R, Shao B, Yan Y, Ran R, Di L. Bilateral breast cancer in China: A 10-year single-center retrospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-13.

Background: Next-generation sequencing is of increasing interest to identify specific targets for both drug development and treatment. The study of metastatic cancer is complicated by lack of tissue and the potential for change in biology over treatment. We evaluated ctDNA in patients with advanced breast cancer to explore the relationship between specific DNA mutations and prognosis as well as therapeutic decision making. Methods:Peripheral blood was collected in EDTA at the time of diagnosis of advanced disease. Samples were sent to Geneplus-Beijing for sequencing. Indexed Illumina libraries were prepared from germline and circulating DNA using the KAPA Library Preparation Kit; the capture probe was designed based on genomic regions selected with 1021 genes, covering the most frequently mutated genes and exons in solid tumors. Clinical characteristics, treatment and outcome data were collected. We analyzed progression free survival (PFS) from first-line therapy and overall survival (OS), endpoints were correlated with observed gene mutations. Results: 54 patients were enrolled; 27 (50%) HER2+, 22 (41%) hormone receptor + (HR+)/HER2-, and 5 (9%) triple negative (TNBC). Median age was 48 (range 26-74). The median follow-up was 8 years (range 12-180 months). First-line therapy included chemotherapy with trastuzumab for HER2+ disease, chemotherapy with endocrine maintenance (17) or endocrine therapy alone (5) for HR+/HER2- disease, and chemotherapy for TNBC. Mutations were found in TP53, PIK3CA, PIK3CA 3140 A>G(p.H1047R) and ERBB (including ERBB1-4), at 40.7%, 35.2%, 20.4% and 25.9%, respectively. In univariate analysis, patients with tumor mutations in TP53 had a shorter OS (median 64 vs 121 months, p=0.006). The PIK3CA 3140 A>G mutation was more frequent in HER2+ (7/27, 25.9%) than HR+/HER2- (4/22 (18.2%) or TNBC (0/5), and was associated with shorter median PFS in HER2+ disease (mutant vs. wild type: 4 (range 2-9) vs. 8 (range 2-22) months, p=0.006). The frequency of ERBB mutation was similar in HER2- 7/27(25.9%) (p=0.707) or HER2+ 7/27(25.9%) disease (p=0.066); there was no significant impact on PFS in any subset. Multivariate analysis for HER2+ disease including age, ER, Ki67, TP53, PIK3CA, PIK3CA 3140 A>G and ERBB), demonstrated that the PIK3CA 3140 A>G mutation was the only factor associated with shorter PFS (p=0.025); further analysis by receiver operating characteristic (ROC) curve showed that the PIK3CA 3140 A>G mutation and the mutation in PIK3CA 3140 A>G and ERBB combination pathway had a large area under the curve (AUC), with AUC of 0.789, and 0.734 respectively. Conclusions: Using NGS in ctDNA, we found that the PIK3CA 3140A>G mutation was more frequent in HER2+ disease, and was the only mutation associated with shorter PFS on multivariate analysis. The presence of a TP53 mutation was associated with worse OS. Evaluation of ctDNA is feasible in a general breast cancer population and has prognostic impact; further correlation of these findings with tumor samples is ongoing. Citation Format: Li H, Wang J, Rugo HS, Zhang Y, Yang L, Liu X, Shao B, Xu Y, Yang L, Zhang R, Ran R, Chang L. Biomarker analysis by next generation circulating tumor DNA (ctDNA) sequencing in patients with advanced breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-02-06.