DoD Breast Cancer, Breakthrough Award Levels 1 and 2

The intent of the Breakthrough Award is to support promising research that has high potential to lead to or make breakthroughs in breast cancer. The critical components of this award mechanism are:

Impact: Research supported by the Breakthrough Award will have the potential for a major impact and accelerate progress toward ending breast cancer. The impact may be near-term or long-term, but must move beyond a minor advancement and have the potential to lead to a fundamentally new approach that is significantly more effective than interventions already approved or in clinical development. Applications are expected to identify the breast cancer patients or at-risk individuals who would ultimately benefit from the proposed research.

Research Scope: The Breakthrough Award is structured with four different funding levels. The levels are designed to support major (but not all) stages of research that will lead to clinical application. Each level has a defined research scope. It is the responsibility of the Principal Investigator (PI) to select the level that aligns with the scope of the proposed research. The funding level should be selected based on the research scope defined in the program announcement, and not on the amount of the budget.

The current program announcement discusses the Breakthrough Award Levels 1 and 2. Funding Levels 3 and 4 are available under other program announcements (HT9425-23-BCRP-BTA3-2 and HT9425-23-BCRP-BTA4-2, respectively). The PI is strongly encouraged to review the research scope defined under each funding level as described in the corresponding Breakthrough Award program announcement before submitting the pre-application. An application that does not meet the intent of the funding level selected will not be recommended for funding, even if it might meet the intent of a different funding level.

The following are general descriptions, although not all-inclusive, of the scope of research projects that would be appropriate to propose under the current program announcement:

· Funding Level 1: Innovative, high-risk/high-reward research that is in the earliest stages of idea development or is an untested theory that addresses an important problem. To foster research that yields new avenues of investigation, preliminary data are not required. Proof of concept is the anticipated outcome.

· Funding Level 2: Research that is already supported by substantial preliminary or published data and strongly validates clinical translation in a well-defined context within the breast cancer landscape.

· Funding Level 2: Population Science and Prevention Studies: Population Science and Prevention Studies should involve investigations into why certain human patient populations differ in cancer risk or clinical prognosis. The studies should focus on the analysis of human data and biospecimens. Research should be already supported by substantial preliminary or published data and strongly validate clinical translation in a well-defined context within the breast cancer landscape. With compelling justification, population science and prevention studies may request higher levels of funding and an additional year in the period of performance.

Partnering PI Option: The Breakthrough Award encourages applications that include meaningful and productive partnerships between investigators. The Partnering PI Option is structured to accommodate two PIs. One PI will be identified as the Initiating PI and will be responsible for the majority of the administrative tasks associated with application submission. The other PI will be identified as a Partnering PI. Both PIs should contribute significantly to the development of the proposed research project, including the Project Narrative, Statement of Work (SOW), and other required components. The PIs may have expertise in similar or disparate scientific disciplines, but each PI is expected to bring distinct contributions to the application. The application should clearly demonstrate that both PIs have equal intellectual input into the design of the project and will devote similar and appropriate levels of effort to the conduct of the project. It is expected that funding will be balanced between both PIs unless appropriately justified. New partnerships are encouraged, but not required. The application is expected to describe how the PIs’ unique expertise combined as a partnership will better address the research question, how the unique expertise that each individual brings to the application is critical for the research strategy and completion of the SOW, and why the work should be done together rather than through separate efforts. To meet the intent of the Partnering PI Option, applicants are discouraged from being named as a Partnering PI on multiple Breakthrough Award Levels 1 and 2 applications unless they are clearly unique, meaningful partnerships addressing distinct research questions. Applications in which a mentor and their current postdoctoral fellow or junior investigator are named as Initiating and Partnering PIs do not meet the intent of the Partnering PI Option. Applications where one PI is providing samples, animal models, or investigational agents while the other PI is conducting most or all of the experiments and analyses do not meet the intent of the Partnering PI Option. If recommended for funding, each PI will be named to an individual award within the recipient organization. For individual submission requirements for the Initiating and Partnering PI, refer to Section II.D.2, Content and Form of the Application Submission .

Personnel: Applications are expected to include an appropriate and robust research team with the combined backgrounds and breast cancer-related expertise to enable successful conduct of the project.