Abstract P3-10-16: Predicting pathological complete response by the combination of microRNAs in patients with HER2-positive primary breast cancer who received neoadjuvant combination therapy of trastuzumab, lapatinib and paclitaxel: Results from JBCRG-16 (NeoLath) study
Authors: Shimomura A , Masuda N , Kawauchi J , Takizawa S , Ichikawa M , Matasuzaki J , Kuroi K , Hara H , Yamamoto N , Inoue K , Suganuma N , Aogi K , Ohno S , Tamura K , Ochiya T , Toi M 
Published: May 2019

Abstract
[Background] JBCRG-16 (NeoLath) study is a five-arm study to evaluate the efficacy and safety of lapatinib and trastuzumab (6 weeks) followed by lapatinib and trastuzumab plus weekly paclitaxel (12 weeks) with/without prolongation of anti-HER2 therapy prior to chemotherapy (18 vs. 6 weeks), and with/without endocrine therapy in patients with HER2+ and/or estrogen receptor (ER)+ disease. The primary endpoint was pathological complete response (pCR) rate and pCR rate was 47.9% (Masuda N, et al. Breast Cancer, 2018). It is recently reported that microRNAs (miRNAs) are stably present in serum and potentially useful in the diagnosis and evaluation of treatment of cancer. We performed exploratory analysis of detecting pCR by comprehensive analysis of serum miRNAs.
[Materials and Methods] Serum samples were obtained from study participants who received neoadjuvant systemic therapy with trastuzumab, lapatinib and paclitaxel. Before profiling of miRNAs, the overall serum samples were randomly devided in two sets, namely the training set and the testing set with pCR or non-pCR. Pathological complete response (pCR) was defined as the absence of residual invasive cancer of the resected breast specimen and all sampled regional lymph nodes. Total RNA was extracted from a 300 ul serum sample using 3D-Gene® RNA extraction reagent from a liquid sample kit. A comprehensive quantitative expression analysis of miRNA was performed using the by DNA chip 3D-Gene®, which was designed to detect 2565 miRNA sequences registered in miRBase release 21 (http://www.mirbase.org/). The expression level of miRNAs were normalized by internal control (miR-2861, miR-149-3p and miR-4463). Clinicopathological data was retrieved from trial data.
[Results] A total of 112 samples were obtained. Seventy were used in the training set and others were used in the testing set. Median age was 54 years (range 26-70). Sixty-five (58%) patients were pre-menopausal. ER was positive in 59 patients (52.7%). Fourteen (12.5%) were T1c, 78 (69.6%) were T2 and 20 (17.9%) were T3. Fifty-seven (50.9%) patients were node-positive. Fifty-nine (52.7%) patients achieved pCR. The formula with the combination of three miRNAs (miR-A, miR-B, miR-C) was found to be able to predict pCR. This set had a sensitivity of 62.5%, specificity of 86.7% and accuracy of 71.8% in the testing cohort. Area under curve of receiver operationg characteristic curve was 0.753.
[Conclusion] The combination of three miRNAs has potential to predict pCR in patients who received neoadjuvant combination therapy of trastuzumab, lapatinib and paclitaxel in HER2-positive primary breast cancer. The further analysis of changing expression of miRNAs during neoadjuvant therapy is underway and further results will be presented in the symposium.
Citation Format: Shimomura A, Masuda N, Kawauchi J, Takizawa S, Ichikawa M, Matasuzaki J, Kuroi K, Hara H, Yamamoto N, Inoue K, Suganuma N, Aogi K, Ohno S, Tamura K, Ochiya T, Toi M. Predicting pathological complete response by the combination of microRNAs in patients with HER2-positive primary breast cancer who received neoadjuvant combination therapy of trastuzumab, lapatinib and paclitaxel: Results from JBCRG-16 (NeoLath) study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-16.