Shortening Adjuvant Photon and Proton Irradiation (SAPPHIRe-II): A 4 Cohort, Randomized, Phase II Multi-center Trial Evaluating Shorter Schedules of Adjuvant Regional Nodal Irradiation Among Women and Men With Node-positive and High-risk Node-negative Invasive Breast Cancer (NCT07076485)

Check every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).

1. Eligibility Criteria Applicable to All Cohorts Histologically confirmed invasive breast cancer (nodal involvement from presumed invasive breast cancer in the setting of occult breast cancer is sufficient to meet this criteria) 1\. Regional nodal irradiation recommended by treating radiation oncologist. 2 Negative final surgical margins. 3 No more than 12 weeks have elapsed since final breast/lymph node surgery for patients treated with surgery alone or neoadjuvant chemotherapy. No more than 12 weeks have elapsed since final cytotoxic chemotherapy for patients who received adjuvant chemotherapy. 5. Age ≥18 years. Because breast cancer is exceedingly rare in patients \< 18 years of age, children are excluded from this study. 6. Patients with a prior or concurrent malignancy are eligible provided that the natural history and treatment of the prior or concurrent malignancy does not interfere with the safety or efficacy assessment of the investigational radiation regimen used in this trial. 7. Ability to understand and the willingness to sign a written informed consent document. 8. Concurrent enrollment on other observational, translational, or therapeutic studies is allowed provided there is no direct conflict between the other protocol and the radiation regimen proscribed in this trial. Eligibility Criteria for the Low-Risk Lumpectomy Cohort
2. For patients treated with upfront surgery, pathologic stage pT0-T4b N0-N3a breast cancer without infraclavicular or internal mammary nodal involvement.
3. For patients treated with neoadjuvant chemotherapy, clinical stage cT0-T4b N0-N2a breast cancer.
4. Treated with lumpectomy (or axillary surgery only in the case of occult primary breast cancer)
5. No nodal boost recommended by the treating radiation oncologist. Eligibility Criteria for the High-Risk Lumpectomy Cohort
6. Treated with neoadjuvant chemotherapy
7. Clinical stage cT0-T4b N1-N3a/b/c
8. Treated with lumpectomy (or axillary surgery only in the case of occult primary breast cancer)
9. Nodal boost recommended by the treating radiation oncologist. Eligibility Criteria for the Low-Risk Mastectomy Cohort
10. For patients treated with upfront surgery, pathologic stage T0-T2 N0-N2a
11. For patients treated with neoadjuvant chemotherapy, clinical stage T0-T3 N0- N2a
12. For patients treated with neoadjuvant chemotherapy, residual cellularity of primary tumor ≤ 20%.

🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.

📍 All Participating Trial Locations (4 Sites)

• Banner MD Anderson Northern Colorado — Loveland, Colorado
• Cooper Hospital University Medical Center — Voorhees Township, New Jersey
• The University of Texas M. D. Anderson Cancer Center — Houston, Texas
• University of Texas Health Science Center at San Antonio — San Antonio, Texas

💰 Cost, Insurance & Patient Rights

• 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
• Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
• Voluntary Participation: You may withdraw at any time without affecting your standard medical care.