Abstract Introduction: Over the last three decades, breast cancer survival rates have continued to improve, leading to higher rates of ipsilateral breast events. Many patients prefer to avoid mastectomy, increasing interest in repeat breast-conserving surgery (BCS). The current standard for partial breast re-irradiation is twice daily treatments based on the results of RTOG 1014, which can be burdensome for patients. This study was designed to assess the feasibility, toxicity, and efficacy of daily hypofractionated external beam partial breast re-irradiation following repeat BCS. The primary endpoint is the rate of grade 3+ treatment-related skin, fibrosis, and breast pain adverse events at one-year post-reirradiation, graded by CTCAE criteria. Here, we report preliminary findings. Methods: This is a currently open multicenter, single-arm prospective phase II trial of patients previously treated with breast-conserving surgery (BCS) and adjuvant radiation therapy (all forms eligible). At the time of enrollment, all patients had a unifocal in-breast tumor recurrence or new primary histologically confirmed invasive ductal carcinoma or DCIS, measuring less than 3 cm with negative margins defined as no tumor on ink after repeat BCS. Patients received 40.05 Gy in 15 daily fractions of 2.67 Gy. For patients with high-risk features (young age, poor biology, close margins, high grade), felt to benefit from a boost, an SIB to a smaller margin of 48 Gy was delivered. Follow-up data and patient surveys are collected at 1, 3, 6, 9, 12 months and 3 years. Overall cosmesis is evaluated at 1 and 3 years using the BCTOS quality of life questionnaire (ePRO), the Global Cosmesis Score (ePRO), and the Worksheet for Breast Condition (ePRO). Results: Between October 2023 and June 2025, 16 patients were screened, and 13 were enrolled. Among the 3 patients who declined enrollment, 2 opted for treatment at a facility closer to home that did not support clinical trial participation, while 1 was deemed ineligible. All three received daily fractionated treatment off protocol. One enrolled patient withdrew consent prior to initiating treatment. Ten patients completed treatment and reached the 30-day follow-up mark. Of these, 9 had baseline cosmetic assessments: 11% reported excellent cosmesis, 44% good, 22% fair, and 22% poor. At 30 days, 10 patients had follow-up cosmetic evaluations: 10% reported excellent cosmesis, 60% good, and 30% fair. No patients reported worsening cosmetic outcomes at 30 days, and 3 showed improvement. All patients expressed complete satisfaction with their overall treatment experience. Treatments were well tolerated, with no grade 3 acute adverse events related to therapy. No cases of skin desquamation were observed post-reirradiation. Of the 5 patients who reported mild breast pain at 1 month, all had experienced pain at baseline. With regards to acute toxicity, 6 patients developed grade 1 radiation dermatitis, all of which resolved following treatment. Conclusion: To date, the trial has demonstrated strong patient interest and acceptance, with treatment being well-tolerated. No acute Grade 3 adverse events have been observed and all patients expressed overall satisfaction with the treatment experience. If outcomes are comparable to the current standard of care, this approach may provide a more convenient alternative and potentially improve acceptance of repeat breast-conserving therapy. Longer-term follow-up will be necessary to evaluate late cosmetic outcomes, chronic adverse events and efficacy. Citation Format: C. Pisano, Y. Sun, C. Speers, A. Amin, C. Shah, A. Montero, P. Li, A. Simpson, L. Rock, M. Miller, R. Tendulkar, J. Lyons. Preliminary Findings of Repeat Breast Conserving Surgery Followed by Daily Partial Irradiation for Participants with Ipsilateral Breast Tumor Recurrences or new Ipsilateral Primary Breast Cancer, Treated Previously with Breast Conserving Surgery and with Whole Breast Radiation Therapy abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD12-11.
Pisano et al. (2026) studied this question.