Jitwatcharakomol T.Gokun Y.Daniel S.J.Mestres-Villanueva M.Young R.L.Eckstein J.M.Andraos T.Y.Healy E.H.White J.R.Bazan J.G.Kumar P.Cochran E.R.Beyer S.J.Jhawar S.R.Mahidol University2026-04-102026-04-102026-12-01Breast Cancer Research Vol.28 No.1 (2026)14655411https://repository.li.mahidol.ac.th/handle/123456789/116064Background: Accelerated partial breast irradiation (APBI) has shown non-inferior local control compared to whole breast irradiation, but the optimal external-beam regimen is unclear. This study compares two APBI schedules used at our institution: 38.5 Gy in 10 twice-daily fractions and 28.5 Gy in 5 once-daily fractions delivered every other day. Methods: This retrospective, single-institution study includes post-menopausal women with ductal carcinoma in-situ (DCIS) and early-stage hormone receptor positive invasive breast cancer who underwent lumpectomy followed by APBI and endocrine therapy. Outcomes of interest include ipsilateral breast tumor recurrence (IBTR), disease-free survival (DFS), overall survival (OS), radiation toxicities (graded by CTCAE v5.0), and physician-reported (Harvard scale) cosmetic outcomes. Results: A total of 399 patients were eligible: 142 in the 38.5 Gy group and 257 in the 28.5 Gy group. The median age was 66 years. Most patients had T1 tumors or DCIS (97.4%), were treated with 3D-conformal radiation (99.2%) in the prone position (96.0%), and initiated adjuvant endocrine therapy (86.0%). With a median follow-up of 3.4 years, 3-year IBTR was low and comparable (1% for 38.5 Gy vs. 2% for 28.5 Gy; P = 0.46). Three-year DFS was 99% vs. 98% (P = 0.79) and OS was 99% in both groups (P = 0.53). For acute toxicity, grade 1–2 dermatitis was significantly more common in the 38.5 Gy group (61.7% vs. 28.6%, P < 0.01). For late toxicity at 1-year post-treatment, grade 1–2 skin hyperpigmentation (79.5% vs. 32.4%, P < 0.01) and fibrosis (81.6% vs. 51%, P < 0.01) were significantly more common in the 38.5 Gy group than 28.5 Gy group, respectively. No grade ≥ 3 acute or late toxicities were observed. Cosmetic outcomes were similarly excellent. At 1 year, excellent or good cosmesis was observed in 99% of patients in the 38.5 Gy group and 98% in the 28.5 Gy group (P = 0.15), and at 3 years in 97.3% and 94.1%, respectively (P = 0.83). Conclusions: Both regimens—38.5 Gy in 10 twice-daily fractions and 28.5 Gy in 5 once-daily fractions—delivered using 3D-conformal technique in the prone position yielded excellent 3-year outcomes. Nonetheless, the 28.5 Gy regimen demonstrated a lower incidence of acute and late toxicity and may be preferable in this patient population given its lower skin toxicity and increased convenience. Longer follow-up is warranted to confirm these findings.Biochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1186/s13058-026-02243-62-s2.0-1050344138651465542X41731602