Circulating Tumor microRNA as Predictive Biomarkers in HER2+ Breast Cancer

Circulating tumor microRNA (ct-miRNA) signatures might discriminate between neoadjuvant chemotherapy-responsive and -unresponsive HER2+ breast cancers, according to an analysis of a study presented at the 2016 San Antonio Breast Cancer Symposium.

“Four ct-miRNA signatures were found to identify patients with and without pCR [pathological complete response] in a time- and treatment-specific manner,” reported lead study author Serena Di Cosimo, MD, of the Daidone MG Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy. “Results obtained early post-treatment are of special value: women with unfavorable miRNA signatures can be expected to have poor response after just 2 weeks of treatment.”

So far, the ct-miRNA signatures overall correlate with pCR but not event-free survival (EFS). One ct-miRNA signature, however, 140-5p, does appear at week 2 to be associated with EFS among patients treated with trastuzumab (hazard ratio [HR] 0.40; 95% CI: 0.18-0.89).

“A significant portion of breast cancer patients treated in the neoadjuvant setting do not achieve a pCR and have an increased risk of relapse after surgery,” Dr Di Cosimo noted. Researchers are therefore exploring different circulating tumor biomarkers that might allow noninvasive prediction of treatment outcomes. miRNAs are small, non-protein-coding, gene-regulating RNAs that are shed from tumor cells into the bloodstream; they are “stable and detectable in many biological fluids,” Dr Di Cosimo said. They are therefore attractive candidates for noninvasive “liquid biopsies.”

The NeoALTTO (ClinicalTrials.gov Identifier: NCT00553358) study of neoadjuvant paclitaxel, lapatinib, and trastuzumab included collection of circulating tumor cells and microRNA analysis. The research team evaluated whether ct-miRNAs predict clinical outcomes in neoadjuvant therapy.

Patient plasma was taken at baseline and week 2 of the study for 435 patients; tumor miRNAs were identified using reverse-transcription PCR.

“ct-miRNA signatures at baseline were associated with pCR” in all three NeoALTTO study arms, at baseline and week 2, Dr Di Cosima reported.

The team plans independent validation studies.

Reference

1. Di Cosimo S, Appierto V, Tiberio P, et al. Plasma microRNA levels for predicting therapeutic response to neoadjuvant treatment in HER2-positive breast cancer: Results from Neo-ALTTO. Paper presented at: 39^th San Antonio Breast Cancer Symposium; Dec 2016; San Antonio, TX.