In our study we found that HER mutant lung cancers

In our study, we found that HER2-mutant lung cancers occurred commonly in female patients with an advanced stage at time of diagnosis and in a relatively younger age group. Previously, Mazières et al. [8] obtained comparable epidemiological findings, including a median age of 60 years, a high proportion of women (69%), and a high proportion of stage 4 disease at presentation (50%) were found in HER2-mutant NSCLCs. In addition, they SB 216763 and others noted similar observations regarding the predilection of patients with HER2-mutant lung cancers to present in younger females with predominantly stage 4 disease at the time of diagnosis, in addition to a history of minimal to no tobacco exposure [8, 32, 33]. Radiologically, our study also showed that HER2-mutant tumors were significantly associated with a preference for peripheral location, solid consistency, and spiculated contour. When HER2-mutant tumors were compared with the KRAS-mutant control group, they were significantly smaller in size, associated with pleural retractions, more frequent air bronchograms, and a prevalence of pleural tags. In addition, more local (ipsilateral hilar, N1 level) and N3 adenopathy were found with HER2-mutant tumors versus the KRAS-mutant control group. The preponderance of pleural tags and retractions in HER2-mutant adenocarcinoma might point toward its locally-invasive nature. Furthermore, the more frequent nodal involvement might also point toward the aggressive behavior and early nodal spread of these tumors. In fact, a plausible analogy can be drawn with inflammatory breast cancer which exhibits HER2 amplification in approximately 40% of cases [34], and which tends to pursue an aggressive course with lymphangitic spread, pleural disease, and local invasion. A meta-analysis conducted by Elias et al. regarding the various radiologic characteristics of HER2-positive breast cancers shows the strong association between HER2 overexpression and indistinct masses with irregular margins on mammography, ultrasound, and magnetic resonance imaging [25]. The major limitations of our study are the relatively small sample size and its retrospective nature. Because of the low incidence of these genomic events, larger multicenter trials will be required to better describe and consolidate these radiological findings. Moreover, due to the relatively small sample size and the limited pool of controls, we did not adjust for multiple testing due to the exploratory nature of the study; therefore, results should be interpreted with caution, and validation is needed in future studies. In addition, the prevalence of an advanced stage at time of diagnosis (stage 4) for the HER2-mutant and control groups might represent a confounding factor due to lead time bias, since with advanced stage, different radiological features may overlap and co-exist irrespective of the oncogene. By stage-matching the patients, we tried to diminish such possible effects. On another note, the studied CT scans show a varying slice thickness from 0.625 mm to 5 mm, so that lack of thin slices in some scans might have limited evaluation of tumor features. Finally, the wide array of HER2 mutation subtypes might represent an intrinsic heterogeneity factor in our studied group; an interesting area for future studies is to delve into the most common and significant molecular dysregulations of the HER2 oncogene such as exon 20 insertion YVMA [16]. In conclusion, lung adenocarcinomas harboring HER2 mutation display several radiological features that may highlight the aggressive behavior of the primary tumor and its nodal metastatic spread. Moreover, it shares many of its epidemiological and radiographic characteristics with adenocarcinomas harboring other mutations (such as those involving KRAS and EGFR). The continuous advances in molecular and genomic sequencing, in addition to the growing field of radiogenomics, may play a pivotal role in the future characterization of these tumors radiologically.