Abstract P4-10-26: Protein-protein interaction of HER2 predicts the prognosis of hormone receptor-positive HER2-negative breast cancer
Authors: Choi Hee Jun , Lee Hong Won , Kim Sangmin , Yoon Tae-Young , Kim Hyunwoo , Lee Seul , Nam Seok Jin , Kim Seok Won , Cho Sooyoun , Park Yeon Hee , Lee Jeong Eon 
Published: March 2020

Introduction: Patients with Hormone receptor (HR)-positive / HER2-negtive breast cancer have not received targeted therapy for Her2 based on criteria of the protein expression or DNA copy number amplification. However, the clinical meaning of the level of Her2 signaling activity has not been fully elucidated yet. We recently developed a novel technique of single-molecule protein-protein interaction (PPI) profiling to investigate the importance of HER2 signaling activity in this major subgroup of breast cancer.

Methods: This study is a study with the biospecimen and registered medical record from the prospective collected cohort of Samsung Medical Center, and all of these biospecimens were provided by Samsung Medical Center BioBank. First, We selected 138 of 8463 patients who were diagnosed with invasive breast cancer by curative surgery between January 2008 and December 2013. Specimens were selected based on modified Allred Immunohistochemistry (IHC) scores; 6 for hormone receptors (ER/PR+) and 1 for Her2. Then, we applied the single-molecule co-immunoprecipitation, a novel technology determining protein-protein interactions (PPIs), to each selected biospecimen. PPI and expression level for HER2 protein of each tumor extract were analyzed with HER2-PPI-Dx kit. All the measurement were performed using a single-molecule fluorescence imaging equipment. Based on HER2 PPI and expression level analysis, we developed an algorithm based on the 72 patients’ samples which can predict the prognosis of these patients. This algorithm was validated with the samples from the other 66 patients.

Results: In total, 138 samples from each patients (72 in training set and 66 in validation set) were analyzed. The median follow-up time was 68.0 (range: 7-123) months. Single-molecule measurement for HER2 level showed that clinical specimens showed significant differences in HER2-PPI level even though they had the same IHC score (65-fold from 117 patients with ‘HER2 IHC score: 0’ and 33-fold from 21 patients with ‘HER2-IHC score: 1’, respectively). For the training set, by combining HER2 PPI and HER2 protein expression data, we could select 12 patients (17%) as a high level HER2-PPI group. This high level HER2-PPI group showed the significantly poorer disease free survival (DFS) rate compared to that of the low level group (42% for high-level vs. 83% for low-level, p=0.001). For the validation set with the same cutoff, 17 patients (26%) with identified as high level HER2-PPI group. We still found a significantly poorer DFS rate in this group compared to that of the low level group (82% vs. 88%, p=0.033). For total 138 patients set, we found a significantly poorer DFS rate in this group compared to that of the low level group (p=0.014).

Conclusion: Our results showed that HER2 PPI may have an important clinical meaning to identify a high risk of recurrence in the patients with strong HR-positive and HER2-negative breast cancers defined by conventional method. For those patients with high level HER2-PPI, HER2-targeted therapies may be beneficial despite of their HER2-negativity. This will be proved for the future.

Citation Format: Hee Jun Choi, Hong Won Lee, Sangmin Kim, Tae-Young Yoon, Hyunwoo Kim, Seul Lee, Seok Jin Nam, Seok Won Kim, Sooyoun Cho, Yeon Hee Park, Jeong Eon Lee. Protein-protein interaction of HER2 predicts the prognosis of hormone receptor-positive HER2-negative 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 P4-10-26.