Top News in Genetic Testing for Cancer

Four-Gene Signature Identified Triple-Negative Breast Cancer Subgroups: A four-gene signature, which was presented at the 2017 ASCO annual meeting, has been shown to identify a series of triple-negative breast cancer, including one subtype that was responsive to platinum-based chemotherapy in the metastatic setting. Although currently the standard treatment for triple-negative breast cancer is chemotherapy, limited responses in the adjuvant setting are observed. The study authors explain that the findings of this study may offer additional treatment options for patients in the subtype group, which was shown to have distinctive molecular features including the activation of negative regulators of the MAP kinase signaling pathway and enrichment of CD4 and CD8 immune signatures. Read more. Image © Matej Kastelic/Shutterstock.com

Can Breast Surgeons Provide Genetic Counseling? At the 34th Annual Miami Breast Cancer Conference last year, Patrick W. Whitworth, Jr, MD discussed the importance of educated breast cancer surgeons providing genetic counseling to patients in order to meet the growing needs for genetic screening. Identifying genetic mutation carriers will provide patients and their families with information on the need to screen families as well. Establishing the presence of a mutation, or lack thereof, can spare patients unnecessary interventions such as further testing and unnecessary surgical procedures. A single-gene mutation can be associated with more than one cancer, as well as multiple genes associated with one particular cancer, which is helpful in determining patient and familial risk factors. Current panels offer patients testing of more than 30 genes with a cost of around $300. Read more. Image © wavebreakmedia/Shutterstock.com

Precision Medicine Trial Matches Mutations to Treatment: Presented at the 2017 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, the National Cancer Institute (NCI) Molecular Analysis for Therapy Choice (MATCH) trial screened nearly 6,000 patients in just under 2 years and matched 18% of tumors screened with a genetic mutation to one of 30 treatment arms. Lead author Alice Chen explained that the design of the clinical trial is that so patients can be treated based on the molecular aberration, in which the sequencing assay successfully yielded a result 93% of the time, which is well above the industry average of about 80%. The NCI-MATCH trial will expand to another eight arms through early next year, and a pediatric MATCH trial is now open. Read more. Image © anyaivanova/Shutterstock.com

16-Gene Recurrence Score for High-Risk RCC Offers Prognostic Value: A phase III trial confirming the prognostic value of a 16-gene recurrence score (RS) in patients with high-risk renal cell carcinoma (RCC) undergoing treatment with adjuvant sunitinib, was presented by Bernard J. Escudier, MD at the 2017 ASCO annual meeting. Results of the trial revealed that in the placebo group, each 25-unit increase in RS resulted in a recurrence and disease-free survival hazard ratio (HR) of 4.24 (95% CI, 2.31–7.80; P < .0001) and 3.75 (95% CI, 2.13–6.60; P < .001), as opposed to the sunitinib group that had an HR of 2.53 (95% CI, 1.29–4.97; P = .008) and 2.31 (95% CI, 1.20–4.43; P = .014) for sunitinib, respectively. For RCC–specific survival, the HR for placebo patients was 7.21 (95% CI, 2.85–18.21; P < .001), and for sunitinib patients it was 3.33 (95% CI, 1.48–7.49; P = .005). Read more. Image © crystal light/Shutterstock.com

MMR Deficiency Tests Underused in Young Adults With Colorectal Cancer: Results of a newly published study show that testing for mismatch repair (MMR) deficiency, a characteristic of Lynch syndrome, was underused. MMR deficiency is known to affect prognosis and systemic therapy responses. Researchers note there is a persistent lack of testing in high-risk populations, despite well-established guidelines. Researchers identified 152,993 adult colorectal patients diagnosed between 2010 and 2012. MMR deficiency testing was only performed in 28.2% of patients, and several characteristics were associated with increased likelihood of MMR deficiency testing, including higher education level, later diagnosis year, early-stage disease, and number of regional lymph nodes examined. Underuse of testing was associated with older age, those on Medicare or Medicaid and the uninsured status, nonacademic vs academic/research facility type, rectosigmoid or rectal tumor location, unknown grade (odds ratio, 0.61), and nonreceipt of definitive surgery. Read more. Image © hywards/Shutterstock.com

AUA: Prostate Cancer Studies Highlight DNA Repair Gene Involvement: Two studies evaluating genetic mutations in prostate cancer were presented at the Annual Scientific Meeting of the American Urological Association (AUA). In the first study, researchers found that the risk of prostate malignancy was increased substantially in those with BRCA mutations. Researchers noted that the rates of malignancy in both BRCA1 and BRCA2 mutations is higher than the general population of the same aged individuals. The results are suggestive of broadened BRCA-related prostate cancer risk factors outside of a BRCA2 mutation. The second study noted a high rate of mutations among other DNA repair genes after an analysis of 228 cancer samples. Researchers found the most commonly mutated genes to include BRCA2, ATM, MSH6, MSH2, ATR, MLH1, and BRCA1.These results indicated that genomic profiling could potentially identify prostate cancer patients that are platinum and PARP drug-resistant. Read more. Image © lightspring/Shutterstock.com

Pathology Aids in Diagnosis of Hereditary Leiomyomatosis, RCC: Results from a recent study found that there was a significant association in fumarate hydratase mutations and suspicious kidney tumor pathology. This finding may aid in the early diagnosis of hereditary leiomyomatosis and renal cell carcinoma. During the study, researchers noted that testing identified fumarate hydratase mutations in eight (38%) of the 21 patients with suspicious pathology and one patient without. Researchers found that seven of the eight patients with suspicious pathology had kidney cancer, all eight of whom also developed metastatic cancer. Researchers noted that renal tumors specifically were associated with a positive fumarate hydratase mutation, with a sensitivity of 100% and a specificity of 70% in renal suspicious pathology. These findings are indicative of possibility that the use of pathologic features may help clinicians make a diagnosis in the absence of other diagnostic criteria such as skin lesions. Read more. Image © Komsan Loonprom/Shutterstock.com

Genes Influence Outcomes of Treatment Sequences in Clear Cell RCC: An analysis of the RECORD-3 trial could potentially guide treatment-making decisions in those with clear cell renal cell carcinoma, if the genotyping results can be validated. In the RECORD-3 trial, researchers showed an improved survival with the use of sunitinib followed by everolimus at disease progression compared with the reverse sequence of therapy in 471 patients. James J. Hsieh presented his analysis findings at the 15th International Kidney Cancer Symposium and reported a distinct correlation between PBMR1, BAP1, and KDM5 mutations and treatment outcomes. For example, identical progression-free survival (PFS) was seen in patients who received sunitinib or everolimus with PBMR1 mutations, as opposed to those with BAP1 mutations who experienced worse PFS when treated with everolimus first. Additionally, in those with KDM5 mutations, treatment with everolimus yielded identical results to the overall cohort, while patients fared exceptionally well with the sunitinib → everolimus sequence of agents. Read more. Image © bluebay/Shutterstock.com

Mutation Pattern May Help Predict Treatment Response in Urothelial Carcinoma of the Bladder: Similar mutation patterns between primary and recurrent tumors of chemoradiation-treated patients with urothelial carcinoma of the bladder and improved outcome in those with deleterious DNA damage response gene alterations were reported in the results of a study published in 2017. The study which evaluated 48 patients with nonmetastatic, high-grade disease, eight of whom had a matched recurrent tumor, used next-generation sequencing with an assay enriched for cancer-related genes and “canonical” DNA damage response . Results of patterns in genomic alterations was similar to current reports. Their findings noted an association with a trend toward reduced disease recurrence in those with a DDR deleterious alteration on both univariate and multivariate analyses. Alterations in ERCC2 in particular seemed to be associated with lower risk of recurrence, with only one in six patients experiencing a recurrence. Read more. Image © Magic mine/Shutterstock.com

Integrating Genetics, MRD Improves Risk Stratification in Childhood ALL: Results of a population-based cohort study found that the integration of genetic risk factors with minimal residual disease (MRD) improves the accuracy of risk stratification for children with acute lymphoblastic leukemia (ALL). New findings suggest that MRD interpretation should integrate genetic subtypes to more accurately differentiate patients at highest and lowest risk of relapse vs the current protocols, which use one MRD threshold to risk-stratify patients. They found that there was a difference in prognostic implications in MRD values for the different genetic risk categories, which were identified in data analyzed from 3,113 patients treated in the UKALL2003 trial. Patients were divided into four genetic risk categories including: good-risk cytogenetics, intermediate-risk cytogenetics, high-risk cytogenetics, and T-cell ALL. They noted a 5-year overall survival rate of 96% in the good-risk cytogenics group among children with MRD values of 0.01% to < 0.1% compared with 78% for the high-risk cytogenetics group. Read more. Image © BlurryMe/Shutterstock.com

Gene Signature Helped Predict Poor Response to IMiDs in Multiple Myeloma: A model with prognostic value in predicting favorable or unfavorable responses to immunomodulatory derivatives (IMiDs) in patients with multiple myeloma has been developed by researchers in the United States. Researchers identified 176 IMiD response genes during development of the model that were differentially expressed before and after patient exposure to IMiD, 14 of which were combined to create a continuous IMiD-14 score. These 14 genes were found to have significant P values in association with progression-free survival in those with a history of thalidomide induction and maintenance. Those who were found to have a high IMiD-14 score were considered to be IMiD-resistant. Their findings show potential for use of IMiD-14 gene expression signature which can classify patients by risk for progression. This would allow clinicians to offer other effective treatment option completions that may be more effective in this population. Read more. Image © ktsdesign/Shutterstock.com

‘Liquid Biopsy’ Detects DLBCL Gene Copy Number Alterations: Presented at the 2017 ASCO annual meeting, the results of a recent study show that prognostic somatic copy number alterations (SCNAs) in diffuse large B-cell lymphoma (DLBCL) can be detected and monitored noninvasively using circulating tumor DNA (ctDNA) from patient plasma. Plasma samples of 168 patients with DLBCL were analyzed using Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) and genome-wide allele fraction and copy number alteration analyses. Study authors note that the sensitivity and specificity were particularly high in patients with high tumor burden (ctDNA > 5%). Researchers additionally analyzed plasma from patients with Hodgkin lymphoma and primary mediastinal B-cell lymphoma (PMBCL). Genome-wide ctDNA sequencing detected PD-L1 amplification in DLBCL, PMBCL, and classical Hodgkin lymphoma cells, with researchers detecting a high frequency of PD-L1 lesions in DLBCL, which may aid in patient selection for future immunotherapy clinical trials. Read more. Image © Elpisterra/Shutterstock.com

Liquid Biopsy Combo Improved Sensitivity for EGFR Mutations in NSCLC: According to the results of a recently published study, the combination of exosomal RNA (exoRNA) and cell-free DNA (cfDNA) improved the sensitivity of blood-based liquid biopsy for EGFR mutation detection in non-small cell lung cancer (NSCLC) compared with standard circulating tumor DNA (ctDNA). The sensitivity of the exoNA for finding activating EGFR mutations was 98% (53 of 54), as compared to ctDNA, which had a sensitivity of 82% (44 of 54; P = .004). In patients with low-copy T790M (< 10 copies/mL), researchers report a sensitivity of 81% with exoNA and 58% with ctDNA for activating EGFR mutations. There was a noted sensitivity of 61% for T790M mutations with exoNA vs a sensitivity of 53% in ctDNA. The most significant difference was seen in patients with intrathoracic (M0/M1a) disease with a sensitivity for activating mutations of 74% with exoNA and 26% with ctDNA; for T790M mutations the rates were 31% and 19%, respectively. Read more. Image © CI Photos/Shutterstock.com