A woman presented to medical oncology with almost 4 years of untreated, slowly progressing, triple negative metastatic breast cancer to the lung. About 15 years prior, she was diagnosed with invasive ductal carcinoma of the right breast with ipsilateral chest wall recurrence 6 years later. Comprehensive molecular profiling of a metastatic lesion detected a hotspotETV6-NTRK3fusion, which was not present on circulating tumour DNA or molecular profile performed 4 years prior. A second look pathological examination demonstrated tumour characteristics consistent with secretory breast carcinoma. Identification ofETV6­-NKRT3fusion allowed for treatment with larotrectinib, a tyrosine kinase inhibitor specifically indicated for secretory breast carcinoma. After 3 months, she experienced a partial response.

Androgen receptor (AR) is expressed in numerous tissues and serves important biologic functions in skin, prostate, immune, cardiovascular, and neural systems, alongside sexual development. Several studies have associated AR expression and patient survival in various cancers, yet there are limited studies examining the relationship between AR expression and cutaneous melanoma. This study used genomics and proteomics data from The Cancer Proteome Atlas (TCPA) and The Cancer Genome Atlas (TCGA), with 470 cutaneous melanoma patient data points. Cox regression analyses evaluated the association between AR protein level with overall survival and revealed that a higher level of AR protein was positively associated with a better overall survival (OS) (p = 0.003). When stratified by sex, the AR association with OS was only significant for both sexes. The multivariate Cox models with justifications of sex, age of diagnosis, stage of disease, and Breslow depth of the tumor confirmed the AR-OS association in all patients. However, the significance of AR was lost when ulceration was included in the model. When stratified by sex, the multivariate Cox models indicated significant role of AR in OS of female patients but not in males. AR-associated genes were identified and enrichment analysis revealed shared and distinct gene network in male and female patients. Furthermore, AR was found significantly associated with OS in RAS mutant subtypes of melanoma but not in BRAF, NF1, or triple-wild type subtypes of melanoma. Our study may provide insight into the well-known female survival advantage in melanoma patients.

Distinguishing abnormal electroencephalogram (EEG) waveforms from benign variants is critical for accurate interpretation of EEG. Hyperventilation (HV) is one of the basic procedures during EEG to enable activation of epileptiform activity. Rarely, HV can activate benign EEG rhythms. Herein, we illustrate two pediatric cases with bursts of rhythmic mid-temporal theta of drowsiness (RMTD), activated by hyperventilation. Continued awareness of this EEG phenomenology and its variations in pediatrics is important in avoiding misdiagnosis of epilepsy.

This commentary discusses the case from the publication “Metastatic Triple Negative Breast Cancer with NTRK Gene Fusion on Tissue but not on ctDNA Molecular Profile.” This paper stresses the importance of molecular profiling to find characteristic mutations such as NTRK gene fusions which increase therapeutic options including tyrosine receptor kinase inhibitors such as Larotrectinib and entrectinib. The current profiling techniques are also discussed with both advantages and limitations discussed. Genomic testing in relation to current pharmaceutical therapies will shape the future of cancer diagnosis and treatment.