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Summary: The fiscal year 2026 (FY26) Breast Cancer Research Program (BCRP) Breakthrough Award mechanism supports promising research with high potential to lead to or make breakthroughs in breast cancer. All applications must address at least one of the FY26 BCRP overarching challenges or provide adequate justification for exception. Applications must address the challenge in a way that can lead to a breakthrough and have major impact. The FY26 Breakthrough Award mechanism contains four different funding levels designed to support major (but not all) stages of research that will lead to clinical application. Each level specifies a distinct research scope. This program announcement discusses the Breakthrough Award Levels 1 and 2.Distinctive Features:* This funding mechanism allows for applications submitted under Funding Level 1 or Funding Level 2. Funding Level 2 also includes a Population Science Studies option. With compelling justification, population science studies may request higher levels of funding and an additional year in the period of performance.* This funding mechanism allows for a single Principal Investigator (PI), or two partnering PIs referred to as the Initiating PI and the Partnering PI. For the Partnering PI Option (PPIO), only the Initiating PI will submit a pre-application, but both PIs will need to submit at the full application stage. Be advised, failure to submit all associated (Initiating and Partnering PI) applications by the deadline may result in a

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