SABCS 2024

Compared to tissue testing alone, concurrent solid tissue and circulating tumor DNA (ctDNA) testing identified an additional 20% of patients with actionable findings, reducing the need for repeat biopsies and associated adverse events. In a simulated cohort, concurrent testing detected 92 more patients with actionable variants compared to tissue testing alone and prevented 24 additional biopsies at an incremental cost of $2,715 per patient—less than the cost of an extra liquid biopsy. The approach demonstrates an approach for enhancing patient care by improving diagnostic yield and decreasing the number of unnecessary procedures at an incremental cost that is less than the cost of a liquid biopsy.

A retrospective analysis from the Tempus database revealed that patients with Metaplastic breast cancer (MpBC), a rare, aggressive subtype with a dismal prognosis, had a distinct molecular phenotype compared to non-MpBC. In patients with MpBC, there was a higher prevalence of triple-negative breast cancer (TNBC), and a distinct somatic alteration profile. Somatic alterations in TERT, CDKN2A/B, MTAP and genes involved in the PI3k pathway were more common in MpBC, compared to non-MpBC patients, providing insights into potential therapeutic targets. The study also found a unique tumor immune microenvironment in MpBC, primarily characterized by a higher PD-L1 expression.These analyses provide further rationale to develop new biomarker-selected treatment strategies in a subtype that is challenging to treat and under-represented in trials.

In a study of patients with HR+/HER2- metastatic breast cancer (HR+ MBC), low-level AURKA copy number gains were found to be common and associated with resistance to CDK4/6 inhibitors (CDK4/6i). The Tempus database was used to analyze genomic records from tumors sequenced with the Tempus xT DNA seq and xR RNA seq assays, revealing that 15% of patients had AURKA amplifications, which are not typically reported by standard sequencing platforms. Findings showed that patients with AURKA amplifications had significantly shorter progression-free survival (9.9 months) on CDK4/6i compared to those without (17 months), suggesting that AURKA amplification is a potential marker of CDK4/6i resistance. This research underscores the importance of identifying low-level AURKA gains, as they could inform more personalized use of emerging AURKA-targeted therapies like alisertib and further studies are needed.