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As germline testing for breast cancer risk genes becomes increasingly common, clinicians face a challenge integrating testing results and breast cancer care. While there are clear guidelines for treating different breast tumors, how genetic testing might alter the actions of clinicians and patients is unclear. In practice, genetic testing and the interpretation of results is not uniformly applied, which could significantly affect treatment. In a recent article in JAMA Oncology (https://doi.org/10.1001/jamaoncol.2019.6400), Kurian et al. show that when genetic testing finds a pathogenic variant in breast cancer patients, the subsequent treatment is less adherent to practice guidelines. The researchers examined data from the Georgia and California Surveillance, Epidemiology and End Results (SEER) Genetic Testing Linkage Initiative, which linked treatment data, including one year of follow-up, with genetic data of more than 20,000 women. Only genes designated as breast cancer–associated by the National Comprehensive Cancer Network’s guidelines were considered. Those guidelines, along with tumor characteristics, were used to determine the recommended treatment, which was then compared with actual treatment. Instead of adhering to guidelines, the researchers found an overall pattern in patients with a pathogenic variant: overuse of bilateral mastectomy, underuse of radiotherapy after lumpectomy, and overuse of chemotherapy. In patients eligible for unilateral mastectomy, those with a pathogenic variant underwent a bilateral procedure more often (62% for BRCA1/2, 44% for other variants) than those with a negative or variant of unknown significance (VUS) result (24%). This result is consistent with previous research that links genetic test results and extensiveness of surgery, and reflects practice guidelines that advise discussing bilateral mastectomy for BRCA1/2, PTEN, and TP53 carriers. The significant difference in radiotherapy treatment rates for those with BRCA1/2 (50%) versus those without this variant (76–82%) could be caused by concern of increased cancer risk or toxic effects caused by radiotherapy. The researchers suggest that this striking gap may also reflect patients with BRCA1/2 who opt for a mastectomy in the future rather than conserving breast tissue with radiotherapy. While patients eligible to forgo chemotherapy received it more often if they had BRCA1/2 (53%, compared with 27–32%), when other decision-making factors were considered in the analysis (age, stage, grade, and recurrence score), the rate dropped to 38%. This suggests that clinicians don’t exclusively consider genetic test results in chemotherapy decision-making. The authors conclude that genetic testing is already significantly integrated into breast cancer treatment; thus, evaluation of how testing impacts treatment should continue. —A. N. Grennell, News Editor Autism spectrum disorder (ASD) affects 1 in 160 children globally, according to the World Health Organization, and its prevalence appears to be increasing. Yet there are still many unanswered questions about the altered neurodevelopment and neurophysiology of the disorder: when and where it occurs and what cell types it affects. The genetic underpinnings of ASD can provide powerful insights to help answer these questions. Examining the prevalence of rare variants in populations with and without ASD can implicate specific genes as risk factors for ASD. In a recent article in Cell (https://doi.org/10.1016/j.cell.2019.12.036), Satterstrom et al. present the largest exome sequencing study of ASD to date, performed by the Autism Sequencing Consortium, an international team that pooled data at 50 different sites to create a database with more than 35,000 samples, including nearly 12,000 from patients with ASD. The team compared exomes of those with ASD with those of controls, including a set of 21,000 family-based samples and 14,000 case–control samples. Three types of variants (de novo, inherited, and case–control) were integrated using a refined Bayesian analytic framework, which resulted in 102 genes identified as ASD-associated—a significant increase from the 65 risk genes found in a 2015 study. Because ASD is often comorbid with neurodevelopmental delay (NDD), 49 of these genes were already associated with NDD. However, based on separating the data by phenotypic effect (ASD-predominant or NDD-predominant), 50 genes were found to lead to ASD more frequently than NDD. Identifying these genes can help researchers separate ASD and NDD in future studies. The risk genes were also divided into functional roles: those involved in gene expression regulation (GER) and those involved in neuronal communication (NC). By examining enrichment of GER and NC genes in different brain tissues and stages of fetal and postnatal development, the team found that ASD genes are expressed at higher levels in the cortex and at early developmental stages. Thus, disruptions in brain development and in brain function can lead to ASD. Enriched expression of the risk genes in the prenatal human forebrain also showed that both excitatory and inhibitory neurons are affected in ASD. The authors conclude that a number of disruptions in neuronal function and brain development can lead to autism, and how these neurobiological trajectories converge to result in ASD should be the focus of further genetic investigations. —A. N. Grennell, News Editor