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

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)

Inclusion criteria

• Female ≥40 years with histologically confirmed unilateral invasive breast cancer.
• No suspicious nodal metastasis on preoperative axillary ultrasound (cN0).
• Single lesion in the affected breast on preoperative breast ultrasound and mammography.
• Treated with breast-conserving surgery with pathologically negative margins for the invasive tumor.
• Sentinel lymph node biopsy not performed at surgery (pNx).
• Maximum diameter of invasive tumor ≤2 cm on final pathology (pT1).
• Histologic grade 1 or 2.
• Signed informed consent prior to enrollment.

Exclusion criteria

• History of malignancy other than breast cancer within 5 years (except adequately treated non-melanoma skin cancer, or carcinoma in situ excluding breast carcinoma in situ).
• Preoperative diagnosis of carcinoma in situ without axillary nodal sampling, subsequently diagnosed as invasive breast cancer on final pathology with SLNB omitted.
• Lymphovascular invasion present (LVI+).
• Multifocal or multicentric tumor in the same breast confirmed radiologically or pathologically.
• Bilateral or inflammatory breast cancer.
• Prior radiotherapy to the breast or thorax.
• Confirmed pathogenic or likely pathogenic variant in a hereditary breast cancer gene (including BRCA1/2).
• Recurrent breast cancer.