Abstract P2-08-09: Investigation of autoantibodies (AAbs) in HER2+ breast cancer (BC) patients treated in the neo-adjuvant setting
Authors: Collins Denis Martin , Qiu Ji , Blayney Jaine , McCabe Nuala , Kennedy Richard , LaBaer Joshua , Crown John 
Published: March 2022

Background: HER2+ breast cancer is treated with anti-HER2 IgG monoclonal antibody therapies such as trastuzumab and pertuzumab. These antibodies inhibit HER2-driven intracellular signaling and can also be described as a form of passive immunotherapy, engaging effector immune cells in antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). Tumor-associated autoantibodies (AAbs) to tumor neo-antigens can be generated by the adaptive immune response before, or in response to, therapy. There is growing evidence of a functional role for tumor-associated AAbs in the immune response to tumors, with IgG and IgA AAbs capable of mediating ADCC and ADCP. Using the innovative Nucleic Acid-Programmable Protein Array (NAPPA) platform we examined the levels and targets of circulating AAbs to ~1700 human proteins before, during and after treatment in HER2+ breast cancer treated in the neo-adjuvant setting. . Methods: Pre-treatment, On-treatment (pre- Cycle 2) and Post-treatment (post-Cycle 6) serum samples were obtained from HER2+ breast cancer patients (n=19) treated on the ICORG 10-05 clinical trial. Patients were treated with neo-adjuvant chemotherapy (docetaxel (T)/carboplatin (C)) +/- trastuzumab (H), lapatinib (L) or HL, TCH n=9, TCHL n= 7, TCL n=3. Patients were classified as having a pathological complete response (pCR, n=6), a partial response (PR, n=6) or a non-response (NR, n=7) to treatment. IgG and IgA autoantibody levels were determined using the HD-NAPPA system, focussing on a subset of ~ 1700 human protein targets. A normalised intensity score of &gt 5 was utilised as a cut-off for detection. Results: 92 IgG AAbs and 29 IgA AAbs were detected in all samples, across all timepoints (n=57). When IgG AAbs were divided by patient response, 26 AAbs unique to pCR, 26 AAbs unique to PR and 16 AAbs unique to NR were detected. 5 IgG AAbs (BCL11B, MAP6, PRDM8, SYTL2, TP53BP2) were common to all HER2+ breast cancer patients. When IgA AAbs were divided by patient response, 11 AAbs unique to pCR, 6 AAbs unique to PR and 7 AAbs unique to NR were detected. 2 IgA AAbs (TDP1 and MAP6) were common to all HER2+ breast cancer patients. Treatment-induced AAbs were detected in On-treatment and Post- treatment samples in 16/19 patients examined. Conclusions: Our results suggest HER2+ BC patients have unique circulating AAbs associated with treatment response and AAb levels change in response to treatment. Further investigation of AAb levels as biomarkers of response in HER2+ BC is warranted in a larger cohort of patients.

Citation Format: Denis Martin Collins, Ji Qiu, Jaine Blayney, Nuala McCabe, Richard Kennedy, Joshua LaBaer, John Crown. Investigation of autoantibodies (AAbs) in HER2+ breast cancer (BC) patients treated in the neo-adjuvant setting [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-09.