Abstract P1-10-28: Role of Sec62 in prediction of response to neoadjuvant chemotherapy in patients with primary breast cancer

Abstract

Abstract Background Chromosome 3q26 amplifications have been shown to represent a frequent alteration in various cancer entities including breast cancer. SEC62 - a 3q26 encoded gene - was identified as a potential oncogene and tumor-driver-gene for the pathogenesis of breast cancer. Although the precise physiological function of the respective protein Sec62 is not completely understood, it is hypothesized, that Sec62 induces an increased stress tolerance and enhances cell migration in SEC62 overexpressing cells resulting in a high rate of lymphatic metastasis and poorer overall prognosis in tumor tissue with a high Sec62 expression. We sought to further elucidate the function of Sec62 in breast cancer with special focus on its predictive role on the response to neoadjuvant chemotherapy. Materials and Methods All patients treated for primary breast cancer with neoadjuvant chemotherapy at the Department of Gynaecology and Obstetrics, Saarland University Hospital, Homburg, Germany between 01/2007 and 12/2018 were enrolled in this study. The study was approved by the Saarland institutional review board. Sec62 protein levels were analyzed in tumor tissue samples using immunohistochemistry (IHC). Sec62 immunoreactivity was evaluated by three independent examiners using the immunoreactive score (IRS) according to Remmele and Stegner (0-12). For the assessment of Sec62 protein expression in tumor cells, we rated Sec62 “negative” 0-3, “low” for a score of 4-8 and “high” for 9-12 as described in previous publications. IHC was performed on initial breast core biopsy (CB) tissue (pre-treatment) and on definite pathology specimen (PS) obtained during breast surgery after completion of neoadjuvant chemotherapy. Sec62 expression in both samples were compared and correlated with response to neoadjuvant chemotherapy evaluated pathologically using the semi-quantitative response to neoadjuvant chemotherapy scoring system by Sinn et al. ranging from 0 (no effect) to 4 (no tumor detectable). Additionally, Sec62 expression in tumor tissue was compared with the histologically tumor-free tissue of the same patient. Sec62 expression levels and correlation with response to neoadjuvant chemotherapy were compared using Wilcoxon signed-rank, Mann-Whitney and Pearson`s chi square test. Results 203 patients were assessed for eligibility. Nine cases were excluded, due to incomplete clinical information or insufficient slide quality, leaving 194 patients for final analysis. Median patient age was 54 (22-86) years and median response to neoadjuvant chemotherapy score of 2 (0-4). 20 patients (10 %) had luminal A, 46 (24 %) luminal B, 60 (31 %) Her2/neu positive and 68 (35 %) triple negative breast cancer. All analyzed slides showed an over-expression of Sec62 in breast cancer cells but no positive staining of physiologic breast tissue cells. Median Sec62 expression in core biopsies (CB) (8 (2-12)) was significantly higher compared to expression in final specimen (PS) (4 (0-12); p ≤ 0.01). Median difference between Sec62 expression of CB and PS was 2 (0-4). Regarding response to neoadjuvant chemotherapy patients with a low Sec62 expression in PS and a difference ≥ 6 between CB and PS showed a significant higher median response score compared to other patients (2 (0-4) vs. 1 (0-2); p ≤ 0.01; 4 (1-4) vs. 1 (0-4); p ≤ 0.01). When looking at breast cancer subtypes these effects were strongest in Her2/positive and triple negative patients and median Sec62 expression showed the highest decrease between CB and PS in these two subgroups (6 (-3-12); 2 (-6-12)). Conclusion We identified Sec62 as a potential biomarker for prediction of response to neoadjuvant chemotherapy in patients with primary breast cancer. This effect was observed to be strongest in patients with Her2/positive and triple negative breast cancer. Citation Format: Julia Caroline Radosa, Mariz Kasoha, Merle Doerk, Barbara Linxweiler, Maximilian Linxweiler, Florian Bochen, Rainer M Bohle, Matthias Wagner, Marc P Radosa, Erich-Franz Solomayer, Zoltan Ferenc Takacs. Role of Sec62 in prediction of response to neoadjuvant chemotherapy in patients with primary breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-28.