Background Sentinel lymph node biopsy is the standard surgical staging approach for operable triple-negative breast cancer (TNBC) with clinically negative axillae. In this study, we sought to develop a model to predict TNBC patients with negative nodal involvement, who would benefit from the exemption of the axillary staging surgery. Materials and Methods We evaluated 3′ untranslated region (3′UTR) profiles using microarray data of TNBC from two Gene Expression Omnibus datasets. Samples from GSE31519 were divided into training set ( n = 164) and validation set ( n = 163), and GSE76275 was used to construct testing set ( n = 164). We built a six-member 3′UTR panel ( ADD2 , COL1A1 , APOL2 , IL21R , PKP2 , and EIF4G3 ) using an elastic net model to estimate the risk of lymph node metastasis (LNM). Receiver operating characteristic and logistic analyses were used to assess the association between the panel and LNM status. Results The six-member 3′UTR-panel showed a high distinguishing power with an area under the curve of 0.712, 0.729, and 0.708 in the training, validation, and testing sets, respectively. After adjustment by tumor size, the 3′UTR panel retained significant predictive power in the training, validation, and testing sets (odds ratio = 4.93, 4.58, and 3.59, respectively; p < .05 for all). A combinatorial analysis of the 3′UTR panel and tumor size yielded an accuracy of 97.2%, 100%, and 100% in training, validation, and testing set, respectively. Conclusion This study established an integrative 3′UTR-based model as a promising predictor for nodal negativity in operable TNBC. Although a prospective study is needed to validate the model, our results may permit a no axillary surgery option for selected patients. Implications for Practice Currently, sentinel lymph node biopsy is the standard approach for surgical staging in breast cancer patients with negative axillae. Prediction estimation for lymph node metastasis of breast cancer relies on clinicopathological characteristics, which is unreliable, especially in triple-negative breast cancer (TNBC)—a highly heterogeneous disease. The authors developed and validated an effective prediction model for the lymph node status of patients with TNBC, which integrates 3′UTR markers and tumor size. This is the first 3′UTR-based model that will help identify TNBC patients with low risk of nodal involvement who are most likely to benefit from exemption axillary surgery.

Testicular cancer is one of the few tumor types that have not yet benefited from targeted therapy. Still no new active agents for treating this cancer have been identified over the past 15 years. Once patients are refractory to cisplatin-based chemotherapy, they will be expected to die from testicular cancer. This report describes a 21-year-old man who was refractory to chemotherapy and immunotherapy. Whole exome sequencing and low-depth whole genome sequencing confirmed the KRAS gene amplification, which may lead to the tumor cells’ progression and proliferation. After discussion at the molecular tumor board, the patient was offered paclitaxel, carboplatin, and sorafenib (CPS) based on a phase III clinical trial of melanoma with KRAS gene copy gains. After treatment with CPS, the patient achieved excellent curative effects. Because of a nearly 50% frequency of KRAS amplification in chemotherapy-refractory testicular germ cells, CPS regimen may provide a new therapy, but it still warrants further validation in clinical studies. Key Points Chemotherapy-refractory testicular cancer has a very poor prognosis resulting in a lack of effective targeted therapies. KRAS gene amplification occurs in nearly 20% of testicular cancer and 50% of chemotherapy-refractory testicular cancer. KRAS amplification may activate the MAPK signaling pathway, and inhibition of MAPK by sorafenib combined with paclitaxel and carboplatin could be a viable option based on a phase III clinical trial of melanoma. To the authors’ knowledge, this is the first report of response to sorafenib-based combination targeted therapy in a patient with chemotherapy-refractory testicular cancer. Clinical genomic profiling can confirm copy number variation of testicular cancer and provide insights on therapeutic options.

Background Non-small cell lung cancer (NSCLC) is one of the most common human malignancies and the leading cause of cancer-related death. Over the past few decades, genomic alterations of cancer driver genes have been identified in NSCLC, and molecular testing and targeted therapies have become standard care for lung cancer patients. Here we studied the unique genomic profile of driver genes in Chinese patients with NSCLC by next-generation sequencing (NGS) assay. Materials and Methods A total of 1,200 Chinese patients with NSCLC were enrolled in this study. The median age was 60 years (range: 26–89), and 83% cases were adenocarcinoma. NGS-based genomic profiling of major lung cancer-related genes was performed on formalin-fixed paraffin-embedded tumor samples and matched blood. Results Approximately 73.9% of patients with NSCLC harbored at least one actionable alteration recommended by the National Comprehensive Cancer Network guideline, including epidermal growth factor receptor ( EGFR ), ALK , ERBB2 , MET , BRAF , RET , and ROS1 . Twenty-seven patients (2.2%) harbored inherited germline mutations of cancer susceptibility genes. The frequencies of EGFR genomic alterations (both mutations and amplification) and ALK rearrangement were identified as 50.1% and 7.8% in Chinese NSCLC populations, respectively, and significantly higher than the Western population. Fifty-six distinct uncommon EGFR mutations other than L858R, exon19del, exon20ins, or T790M were identified in 18.9% of patients with EGFR -mutant NSCLC. About 7.4% of patients harbored both sensitizing and uncommon mutations, and 11.6% of patients harbored only uncommon EGFR mutations. The uncommon EGFR mutations more frequently combined with the genomic alterations of ALK , CDKN2A , NTRK3 , TSC2 , and KRAS . In patients <40 years of age, the ALK -positive percentage was up to 28.2%. Moreover, 3.2% of ALK -positive patients harbored multi ALK rearrangements, and seven new partner genes were identified. Conclusion More unique features of cancer driver genes in Chinese NSCLC were identified by next-generation sequencing. These findings highlighted that NGS technology is more feasible and necessary than other molecular testing methods, and suggested that the special strategies are needed for drug development and targeted therapy for Chinese patients with NSCLC. Implications for Practice Molecular targeted therapy is now the standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). Samples of 1,200 Chinese patients with NSCLC were analyzed through next-generation sequencing to characterize the unique feature of uncommon EGFR mutations and ALK fusion. The results showed that 7.4% of EGFR-mutant patients harbored both sensitizing and uncommon mutations and 11.6% harbored only uncommon mutations. Uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. ALK fusion was more common in younger patients, and the frequency decreased monotonically with age. 3.2% of ALK-positive patients harbored multi ALK rearrangement, and seven new partner genes were identified.