Abstract P4-07-04: Detecting early breast cancer by the combination of five serum microRNAs and its possibility of prediction of pathological complete response in neoadjuvant chemotherapy
Authors: Shimomura A , Shiino S , Kawauchi J , Takizawa S , Sakamoto H , Shimizu C , Takeshita F , Niida S , Kinoshita T , Tamura K , Ochiya T 
Published: March 2017

Abstract
[Background] It is recently reported that microRNAs (miRNAs) are stably present in serum and potentially useful in the diagnosis and evaluation of treatment of cancer.
[Materials and Methods] Serum samples of breast cancer before treatment (n=1280) between 2008 and 2014 were obtained from National Cancer Center Hospital and controls (n=3348) were obtained from collaborative institutes. Additionally, the serum sample of patients who received neoadjuvant chemotherapy (NAC) and surgery between last chemotherapy administration and surgery were collected. A comprehensive quantitative expression analysis of miRNA was performed using the by DNA chip “3D-Gene® (Toray Industries Inc.)” Clinicopathological data was retrieved from medical records. Pathological complete response (pCR) was defined as the absence of residual invasive and in situ cancer of the resected breast specimen and all sampled regional lymph nodes.
[Results] Serum samples before treatment of breast cancer patients (n=74), non-cancer controls and patients with other cancers were used (n=2007) in a training set. The rest except for samples after NAC were used in a test set. The formula with the combination of five miRNAs (miR-1246, miR-1307-3p, miR-4634, miR-6861-5p, and miR-6875-5p) was found to be able to detect breast cancer (BCmiR set). BCmiR set had a sensitivity of 97.3%, specificity of 82.9% and accuracy of 89.7% in the test cohort. BCmiR set could detect breast cancer in the non-invasive stage (sensitivity of 98.0% for Tis).
In the breast cancer patients, 91 patients received NAC and surgery. Median age of NAC patients was 49 years (range 28-77). Forty-two patients were hormone receptor-positive (HR+) and HER2-negative (HER2-), 24 were HR+ and HER2-positive (HER2+), 11 were hormone receptor-negative (HR-) and HER2+ and 14 were HR- and HER2-. pCR was observed in 19 (20.9%) of NAC patients. pCR in each subtypes were 3 (7.7%) in HR+ and HER2-, 6 (33.3%) in HR+ and HER2+, 4 (57.1%) in HR- and HER2+ and 3 (27.3%) in HR- and HER2-. Serum after NAC were obtained from 19 pCR patients and 71 non-pCR patients. When we applied BCmiR set to the serum samples after NAC, the average diagnostic index (cut-off value=0) in pCR patients was significantly lower than that in non-pCR patients (pCR, -0.30±0.84; non-pCR, 0.31±1.15; p=0.03). In fact, 57.9% of pCR patients were classified into non-breast cancer. However, 40.8% of non-pCR patients were misclassified into non-breast cancer.
[Conclusion] The combination of five miRNAs (BCmiR set) measured from serum can be used to detect breast cancer. BCmiR set has potential to predict pCR in patients who received NAC. The further analysis to predict pCR is underway and further results will be presented in the symposium.
Citation Format: Shimomura A, Shiino S, Kawauchi J, Takizawa S, Sakamoto H, Shimizu C, Takeshita F, Niida S, Kinoshita T, Tamura K, Ochiya T. Detecting early breast cancer by the combination of five serum microRNAs and its possibility of prediction of pathological complete response in neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-07-04.