The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy. It refined its earlier approach to the classification and management of luminal disease in the absence of amplification or overexpression of the Human Epidermal growth factor Receptor 2 (HER2) oncogene, while retaining essentially unchanged recommendations for the systemic adjuvant therapy of HER2-positive and ‘triple-negative’ disease. The Panel again accepted that conventional clinico-pathological factors provided a surrogate subtype classification, while noting that in those areas of the world where multi-gene molecular assays are readily available many clinicians prefer to base chemotherapy decisions for patients with luminal disease on these genomic results rather than the surrogate subtype definitions. Several multi-gene molecular assays were recognized as providing accurate and reproducible prognostic information, and in some cases prediction of response to chemotherapy. Cost and availability preclude their application in many environments at the present time. Broad treatment recommendations are presented. Such recommendations do not imply that each Panel member agrees: indeed, among more than 100 questions, only one (trastuzumab duration) commanded 100% agreement. The various recommendations in fact carried differing degrees of support, as reflected in the nuanced wording of the text below and in the votes recorded in supplementary Appendix S1, available at Annals of Oncology online. Detailed decisions on treatment will as always involve clinical consideration of disease extent, host factors, patient preferences and social and economic constraints.

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To characterize the prevalence of BRCA mutations and characteristics of BRCA carriers in China and to update the clinical recommendations for BRCA testing, we conducted a wide screen for BRCA mutations using next-generation sequencing (NGS). A total of 4,034 Chinese subjects were screened for germline BRCA1/2 mutations, including 2,991 breast cancer patients and 1,043 healthy individuals from the community enrolled as controls. We developed an NGS-based approach to perform BRCA1/2 screening. BRCA mutations were identified in 9.1% (232/2,560) of cases with at least one risk factor, in 3.5% (15/431) of sporadic patients and in 0.38% (4/1,043) of healthy controls. The mutation frequency ranged from 8.9 to 15.2% in cohorts with a single risk factor to 16.6-100% in groups with multiple risk factors. We identified 70 novel BRCA mutations. A high frequency of BRCA1 c.5470_5477del was detected, accounting for 13.9% (16/115) of the BRCA1 mutations detected in our study. Clinical characteristics such as family history, invasive carcinoma, negative human epidermal growth factor receptor 2 (HER2), high Ki67 index, lymph node status, and high tumour grade were closely related to BRCA mutations. BRCA2 carriers had poorer disease-free survival among HER2- or hormone receptor-positive patients (hazard ratio = 1.892; 95% confidence interval: 1.132-3.161; p = 0.013). This study shows that BRCA mutation carriers could be frequently identified among breast cancer patients with multiple risk factors. Importantly, we established an NGS-based pipeline for BRCA1/2 testing in clinical practice and strongly suggest that breast cancer patients of premier- and moderate-grade risks receive BRCA1/2 mutations testing in China.

In node-negative breast cancer without adjuvant systemic treatment, Ki67% by DIA, but not subjective counts, is reproducible and prognostically strong. This casts serious doubt on therapeutic guidelines using subjective counts of Ki67.

BackgroundThe majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) have been shown to regulate cancer occurrence and progression. However, the lncRNAs that drive metastasis in cancer patients and their underlying mechanisms are still largely unknown.MethodslncRNAs highly expressed in metastatic lymph nodes were identified by microarray. Survival analysis were made by Kaplan-Meier method. Cell proliferation, migration, and invasion assay was performed to confirm the phenotype of LINC02273. Tail vein model and mammary fat pad model were used for in vivo study. RNA pull-down and RIP assay were used to confirm the interaction of hnRNPL and LINC02273. Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq), RNA-seq, ChIP-seq, and luciferase reporter assay reveal hnRNPL-LINC02273 regulates AGR2. Antisense oligonucleotides were used for in vivo treatment.ResultsWe identified a novel long noncoding RNA LINC02273, whose expression was significantly elevated in metastatic lesions compared to the primary tumors, by genetic screen of matched tumor samples. Increased LINC02273 promoted breast cancer metastasis in vitro and in vivo. We further showed that LINC02273 was stabilized by hnRNPL, a protein increased in metastatic lesions, in breast cancer cells. Mechanistically, hnRNPL-LINC02273 formed a complex which activated AGR2 transcription and promoted cancer metastasis. The recruitment of hnRNPL-LINC02273 complex to AGR2 promoter region epigenetically upregulated AGR2 by augmenting local H3K4me3 and H3K27ac levels. Combination of AGR2 and LINC02273 was an independent prognostic factor for predicting breast cancer patient survival. Moreover, our data revealed that LINC02273-targeting antisense oligonucleotides (ASO) substantially inhibited breast cancer metastasis in vivo.ConclusionsOur findings uncover a key role of LINC02273-hnRNPL-AGR2 axis in breast cancer metastasis and provide potential novel therapeutic targets for metastatic breast cancer intervention.