Partial Breast Irradiation Without Sentinel Lymph Node Biopsy in Low-Risk Early Breast Cancer

Overview

This is a multicenter, randomized, phase III non-inferiority trial in women aged 40 years or older with clinically node-negative (cN0), pathologically pT1 (≤2 cm), grade 1-2, lymphovascular invasion (LVI)-negative invasive breast cancer treated with breast-conserving surgery (BCS) in whom sentinel lymph node biopsy (SLNB) was omitted (pNx). Eligible patients are randomized 1:1 to partial breast irradiation (PBI) or whole breast irradiation (WBI). The primary aim is to determine whether PBI is non-inferior to WBI with respect to the 5-year recurrence-free survival (RFS) rate. Secondary aims include comparison of axillary recurrence, overall survival, locoregional recurrence, treatment-related toxicity, and quality of life between arms.

Background and rationale. PBI has shown oncologic outcomes comparable to WBI in low-risk early breast cancer in several randomized trials (e.g., IMPORT LOW, RAPID, GEC-ESTRO, Florence). Separately, SLNB omission has demonstrated oncologic safety in clinically node-negative patients (e.g., SOUND, INSEMA, BOOG). However, the long-term oncologic safety of combining SLNB omission with PBI has not been established. Because pathologic nodal status is unknown in SLNB-omitted patients, occult nodal micrometastasis cannot be fully excluded despite cN0 status, and the reduced treatment volume of PBI relative to WBI may theoretically increase the risk of axillary or regional nodal recurrence. The strict eligibility criteria (negative axillary ultrasound, pT1, grade 1-2, LVI-negative, single lesion, negative margins) are intended to limit the absolute magnitude of this residual risk. Design. Eligible, consented patients are centrally randomized 1:1 to WBI or PBI, with block randomization stratified by age (\<50 vs ≥50 years), tumor size (≤1 cm vs \>1 cm), and hormone receptor status (HR+/HER2- vs other). Quality assurance. For the first 3 patients enrolled at each participating institution, central review is performed on CT simulation images, CTV/PTV/OAR contours, axillary level I-III contours, treatment plans with dose-volume histograms (DVH), and dose/fractionation data. Central review verifies ESTRO-consistent target definition, OAR contouring adequacy, protocol-compliant dose prescription, PTV coverage and OAR dose constraints, axillary level I-III dosimetry, and confirms that high-tangent technique or regional nodal irradiation (RNI) is not used. Follow-up schedule. V1 (end of RT); V2 (3 weeks post-RT); V3 (6 months); V4 (12 months); V5 (annually, years 2-4); V6 (5 years). Annual mammography and breast ultrasound are performed; additional imaging is performed if recurrence is suspected. Extended follow-up to 10 years is planned for long-term oncologic safety and late toxicity (breast cancer-specific survival, overall survival, late locoregional recurrence, late radiation toxicity)