DoW Breast Cancer, Breakthrough Award Level 4

The Defense Health Agency Breast Cancer Research Program Breakthrough Award Level 4 funding opportunity supports large-scale clinical research projects intended to transform and revolutionize the prevention and clinical management of breast cancer. The program is administered through the Congressionally Directed Medical Research Programs within the Defense Health Agency Research and Development office under delegated authority from the Department of Defense. The Breast Cancer Research Program was originally established by Congress in fiscal year 1992 and has invested more than $4.52 billion in breast cancer research through fiscal year 2025. The fiscal year 2026 appropriation for the overall Breast Cancer Research Program is $145 million. The Breakthrough Award mechanism is intended to accelerate progress toward ending breast cancer by supporting high-impact and clinically relevant research that addresses one or more of the program's overarching challenges, including prevention, metastasis, recurrence, treatment innovation, overdiagnosis, mortality reduction, and understanding breast cancer progression. The Breakthrough Award Level 4 specifically supports large-scale projects and comparative effectiveness clinical trials that can substantially change standards of care or prevention strategies. Clinical trials are mandatory under this funding mechanism, and applicants are expected to demonstrate significant readiness for implementation. Applicants must provide evidence of access to study populations, interventions, clinical reagents, and data resources necessary to execute the proposed trial successfully. If the project involves products regulated by the U.S. Food and Drug Administration or an equivalent international regulatory authority, applicants must demonstrate submission of an Investigational New Drug application, Investigational Device Exemption, or equivalent regulatory filing prior to the full application deadline. The proposed clinical trial is expected to begin within 12 months of award, or within 18 months for studies requiring regulatory agency oversight. Applications are expected to follow rigorous research standards such as CONSORT, SPIRIT, STROBE, and ARRIVE 2.0 guidelines to ensure reproducibility and translational relevance. The funding opportunity allows applications from a wide range of organizations, including domestic and foreign organizations, nonprofit and for-profit entities, public and private institutions, and intramural and extramural Department of War organizations. Independent investigators affiliated with eligible organizations may serve as Principal Investigators regardless of citizenship or nationality. The mechanism also offers a Partnering PI Option that encourages meaningful collaboration between two investigators contributing equally to the intellectual development and execution of the project. Applications under this option require separate full application submissions for the Initiating PI and the Partnering PI. A distinctive requirement of the mechanism is the mandatory inclusion of at least two breast cancer consumer advocates as integral members of the research team throughout planning, implementation, oversight, and evaluation activities. Consumer advocates must be breast cancer survivors actively involved in advocacy organizations and may not be employees of participating organizations. Funding available under this opportunity is approximately $21 million total to support approximately one award. The maximum period of performance is four years. For single PI applications, the total budget cannot exceed $21 million in combined direct and indirect costs over the project period. For Partnering PI Option applications, the combined budgets for both investigators also may not exceed $21 million. Indirect costs must follow negotiated institutional rates, and all direct and indirect subaward costs must be included within the primary award budget. Allowable expenses include travel to scientific meetings, collaboration costs, research subject compensation, reimbursement of participant expenses related to trial participation, and annual milestone meeting attendance. Cost sharing or matching funds are not required for eligibility. The application process consists of a mandatory two-step submission process. Applicants must first submit a pre-application through the Electronic Biomedical Research Application Portal. The pre-application requires narrative responses describing the overarching challenge addressed, the expected breakthrough impact, the transformative nature of the project, the appropriateness of the funding level, and project readiness. Invited applicants then submit a full application through Grants.gov for extramural organizations or eBRAP for intramural Department of War organizations. Required application components include a detailed Project Narrative, Supporting Documentation, Technical Abstract, Lay Abstract, Statement of Work, Study Population Recruitment and Safety Plan, Regulatory Strategy, Study Personnel and Organization documentation, Post-Award Transition Plan, and Impact Statement. Additional required materials include budgets, biographical sketches, current and pending support documentation, and institutional representations. Applications selected for second-stage programmatic review must also participate in an oral presentation consisting of a 10-minute presentation and a 20-minute question-and-answer session. Applications are reviewed through a two-tier process consisting of peer review and programmatic review. Peer review evaluates impact, research strategy and feasibility, recruitment and retention plans, regulatory strategy, transition planning, statistical analysis, ethical considerations, personnel qualifications, and partnership quality where applicable. Programmatic review then considers adherence to funding mechanism intent, portfolio balance, and relative impact. Oral presentation evaluations focus on applicants' understanding of key barriers in breast cancer research, their vision for translating findings into near-term clinical impact, and their leadership capabilities. Important deadlines for the fiscal year 2026 cycle include a pre-application deadline of June 12, 2026, invitation notifications on July 16, 2026, and a full application deadline of September 30, 2026. Peer review is expected in December 2026, followed by programmatic review activities through March 2027, with awards anticipated no later than September 30, 2027. Questions regarding application submission may be directed to the eBRAP Help Desk at help@eBRAP.org or 301-682-5507, while Grants.gov technical support is available at support@grants.gov or 800-518-4726.

Demonstrate clear breakthrough potential beyond incremental advancement; strongly align the project with at least one BCRP overarching challenge; provide strong evidence of clinical trial readiness including study population access and regulatory preparation; integrate consumer advocates meaningfully throughout the project lifecycle; include realistic recruitment and retention mitigation strategies; emphasize translational impact and near-term clinical relevance for breast cancer patients and military populations