Gene expression profiling involved in response to neoadjuvant therapy in breast cancer.

Abstract

e12618 Background: Neoadjuvant systemic therapy for breast cancer is used increasingly but, there is a group of patients which do not benefit from this therapy. With these premises, we stablished that our main objective was to identify differential expression genes patterns in patients (pts) with the ER/PR- Her2+, ER/PR+ Her2+ and triple negative (TN) subtypes breast cancers according to response to neoadjuvant therapy. Methods: RNA from formalin fixed paraffin embedded tumor samples from 54 pts with breast cancer that had received neoadjuvant therapy was extracted with mirVana miRNA isolation kit (Ambion). Patients with TN subtype received neoadjuvant chemotherapy based on anthracyclines and taxanes and patients with the Her2+ subtype received treatment with taxanos-trastuzumab and anthracyclines. The RNA expression levels were identified by ClariomD Asssay (ThermoFisher). Results were analyzed with Transcriptome Analysis Console and with in-house scripts in R (version 3.5.1). Data were corrected and normalized using Robust Multichip Average method from the oligo package. Expression was summarized at gene level using the corresponding annotation for ClariomD array BrainArray. Expression analyses were performed with limma package. A fold change ≥ 2 and p < 0.05 was considered statistically significant. We defined to groups: R (response, RCB 0) and NR (not response, RCB III) pts. Results: The median age of the pts was 52 years and 58% were menopausal and 42% pre-menopausal. Tumor stage were T1 9%, T2 50%, T3 30%, T4 11% and lymph node involvement were N0 31%, N1 41%, N2 24%, N3 4%. We obtained twelve genes differentially expressed in R vs NR groups. Respect to TN, two genes (AC053503.12, C9orf153) were differentially expressed between R (n = 11) and NR (n = 11). In ER/PR+ Her2+ subgroup, NBPF4 showed a differential expression in R (n = 8) vs NR (n = 7). In pts with ER/PR- Her2+, nine genes (DHRS2, SLCO1B3, UGT2B15, RGS2, SULT1E1, MED23, FKBP5, MIEN1, HER2) were differentially expressed in R (n = 10) vs NR (n = 7). We have started a validation in an independent cohort of pts in ER/PR+ Her2+ subgroup, confirming the results previously obtained. Conclusions: We found twelve genes differentially expressed in the different molecular subtypes of breast cancer involved in the response to neoadjuvant therapy. Several of these genes, especially UGT2B15, SULT1E1, FKBP5, MIEN1 and HER2 have been reported as key genes in tumoral processes, such as cell proliferation, invasion and drug resistant pathways, suggesting that its could be good biomarkers of response to neoadjuvant therapy in breast cancer.