Project Summary/Abstract Dr. Ciara O’Sullivan is a medical oncologist focusing on clinical and translational research in breast cancer (BC) and developmental therapeutics. Her research has been supported by an American Society of Clinical Oncology Career Development Award and intramural funding at Mayo Clinic (MC). She develops and conducts clinical trials designed to test new drugs and overcome drug resistance, predominantly in endocrine resistant and HER2-positive (HER2+) BC. Another focus is individualizing systemic treatment for early stage HER2+ BC. She is a member of the Alliance Breast Committee and the MC Institutional Review Board (IRB). She led/is leading 17 NCI sponsored trials and three multisite investigator-initiated trials. Specifically, she is study chair of an FDA registration trial, CompassHER2 RD (CompassHER2 Trials Examining Escalating and De- Escalating Therapy in HER2+ Breast Cancer: Optimizing Treatment in Residual Disease [NCT04457596; A011801]), was PI of ACCRU-BR01, A Phase I/II Trial of Abemaciclib and T-DM1 in Women and Men with HER2+ Advanced or Metastatic Breast Cancer Who Progressed on Treatment with a Taxane, Trastuzumab and Pertuzumab (NCT04351230; closed prematurely in 2022) and Co-PI of PROMISE (A Prospective Study to evaluate the role of Tumor Sequencing in Women Receiving Palbociclib for Advanced Hormone Receptor (HR)-Positive, Breast Cancer [NCT03281902]). She has developed an initiative with MC patient advocates which aims to improve BC care through education and patient-centered clinical trials. Dr. O’Sullivan plans to support the NCTN in the next 5 years through: 1. Continued leadership of A011801, including efforts to optimize accrual of rural and underrepresented minority (URM) populations; 2. Completion of PROMISE trial objectives; 3. Leadership of active industry sponsored trials at MC, as well as upcoming trials; 4. Continued work with BC patient advocates to develop patient focused clinical trials, addressing barriers to participation for rural and URM patients; 5. Acquiring the necessary skillset to become a leader in the MC and Alliance BC Disease Groups. Dr. O’Sullivan aims to improve care for BC patients through personalization of systemic treatment options, investigation of novel therapeutics, development of prognostic and predictive biomarkers and her BC advocacy endeavors. Her long-term goal is to be an internationally recognized Professor of Medical Oncology, maintaining a clinical practice with a research focus on endocrine resistance in HR+ BC, HER2+ BC and BC Advocacy. She is committed to being of service to the NCTN by developing, leading and recruiting patients to NCI sponsored clinical trials, supporting IRBs and scientific review committees, and serving on NCI scientific committees. These activities and the derivatives of her proposed work are aligned with the NCI mission of conducting high-quality cancer research to advance knowledge and improve quantity and quality of life for all on...