Abstract 1501: Exceptional response to anti HER-2 targeted therapy in patient with HER2/neu negative breast cancer with HER2/neu positive CTCs
Authors: Vagia Elena , Davis Andrew , Gerratana Lorenzo , Zhang Qiang , Zhang Youbin , Tenler Marian , de Viveiros Pedro Hermida , Gradishar William , Cristofanilli Massimo 
Published: September 2020

Abstract
Background: Treatment resistance is a major challenge in the management of metastatic breast cancer due to several clinical and molecular factors. Tumor heterogeneity is a very important factor responsible for treatment resistance and failures in solid tumors, including breast cancer. In this disease, several studies demonstrated biomarkers conversions when comparing primary disease and distant recurrence supporting a mandatory repeated tissue biopsy before treatment in advanced setting. Liquid biopsy including circulating tumor cells and circulating tumor DNA has further augmented the chances of capturing tumor heterogeneity and clonal evolution giving invaluable information that can guide treatment selection. We will describe a unique and interesting case, in which molecular evaluation and treatment decision demonstrated the importance of integrating both, tissue-based and liquid biopsy information.
Case Presentation: 65 y.o. post-menopausal Caucasian female with history of R breast DCIS s/p bilateral mastectomy in 2013. She was initially diagnosed in 2006, with had left breast atypical ductal hyperplasia. Afterwards, she was serially monitored with imaging. In 2013, routine mammogram discovered a region of calcifications on her R breast behind the nipple (no imaging report available for review). She had subsequent lumpectomy which revealed DCIS ER+, PR-, HER2-. Mammogram 5 weeks revealed a new lesion in the upper R quadrant. Core needle biopsy revealed DCIS. Had bilateral skin sparing mastectomies with reconstruction, R axillary LN dissection with 0/5 lymph nodes. No evidence of invasive disease on the path report. While being evaluated for new reconstruction repeat scans revealed pulmonary nodules and abnormalities in the R axilla and breast. PET scan demonstrated hypermetabolic R axillary and subpectoral lymph nodes, hypermetabolic focal areas within subcutaneous tissues anterior to the right breast implant extending to the skin surface. R axillary node biopsy revealed breast cancer cells ER+, PR-, HER2-. Received chemotherapy, FEC followed by weekly paclitaxel, and subsequently underwent implant removal and skin and remaining breast tissues removal. Completed RT of the chest wall and axilla and started palbociclib plus letrozole which continued for 15 months with no evidence of disease on serial repeat imaging.PET scan 6 months ago demonstrated liver metastases. Liver bx confirmed metastatic HER2 neg disease.
Blood samples were evaluated for CTCs detection as part of ongoing IRB approved study. More than 60 cells were identified with 40 % of those being HER2 positive.Patient started treatment with docetaxel, trastuzumab, pertuzumab. PET scan after 3 months demonstrated complete resolution of the liver metastases. Repeat CTCs collection demonstrated a total number of CTCs 4 and no HER2 positive cells were detected. Patient continued the same treatment with recent scans without evidence of disease.
Conclusion: This case represents an example of successful treatment selection based on evidence collected from CTCs enumeration and biomarker analysis demonstrating discordance with tissue biopsy. Liquid biopsy, including CTCs and ctDNA provides complementary information to understand complex and heterogeneous tumor biology in advanced breast cancer and allow real-time implementation of precision oncology.
Citation Format: Elena Vagia, Andrew Davis, Lorenzo Gerratana, Qiang Zhang, Youbin Zhang, Marian Tenler, Pedro Hermida de Viveiros, William Gradishar, Massimo Cristofanilli. Exceptional response to anti HER-2 targeted therapy in patient with HER2/neu negative breast cancer with HER2/neu positive CTCs [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1501.