Single-fraction APBI for Early-stage Breast Cancer With Favorable Histological Subtypes (Breast-1F)

This is a prospective, randomized, monocentric, non-inferiority interventional clinical study comparing an Accelerated Partial Breast Irradiation (APBI) for the surgical bed of early-stage breast cancer patients with favorable histological subtypes, using stereotactic radiotherapy in a single dose of 15.5 Gy with Simultaneous Integrated Boost (SIB) to 21 Gy (study treatment, delivered in a single fraction) versus multifractionated radiotherapy of 30 Gy in 5 fractions (standard treatment, delivered in 5 fractions).

The project refers to a study on patients with early-stage breast cancer with pathological Tumor stage (pT) from in situ (pTis) to pT2 up to 3 cm in diameter, and pathological/clinical nodal stage p/cN0, and favorable histology (Luminal A and Luminal B human epidermal growth factor receptor 2 (HER2)-negative subtypes), comparing an APBI treatment delivered with stereotactic radiotherapy to the Planning Target Volume (PTV) of the tumor bed of the breast with a total dose (TD) of 15.5 Gy in one fraction, with simultaneous integrated boost (SIB) to a TD of 21 Gy to the Gross Tumor Volume (GTV) represented by tumor bed, versus 30 Gy in 5 consecutive fractions to the PTV of the tumor bed, according to the standard APBI protocol of the department (Florence protocol).

Eligibility Criteria:
Inclusion Criteria:

1. Histological diagnosis of breast cancer
2. Patients aged ≥40 years
3. Signed informed consent
4. Stage pTis-T2, up to 3 cm in the greatest diameter
5. Luminal A and Luminal B HER2-negative histological subtypes
6. Negative surgical margins (≥ 0.2 cm)
7. Negative lymph nodes at sentinel lymph node biopsy, or alternatively with imaging tests (Positron Emission Tomography (PET)/Computed Tomography (CT) and/or axillary ultrasound, and/or breast Magnetic Resonance Imaging (MRI) with and without contrast), or, in rare cases, where still performed, with axillary dissection
8. Clinical M0 (PET/CT and/or bone scintigraphy and/or abdomen-pelvis CT with and without contrast in suspected patients), within the previous 3 months.
9. Performance Status (PS) Eastern Cooperative Oncology Group (ECOG) ≤2
10. No prior thoracic radiotherapy
11. Fertile women using contraception methods initiated during oncological treatment.

Exclusion Criteria:

1. Patients aged \< 40 years
2. Tumors \> 3 cm
3. Multicentric tumors
4. Positive or close surgical margins (\<0.2 cm)
5. Lobular carcinoma
6. Negative hormone receptors
7. HER2-positive
8. BReast CAncer (BRCA) genes BRCA1 and/or BRCA2 positive (only if known)
9. Severe systemic diseases
10. Psychiatric or other disorders that may prevent the patient from signing informed consent
11. Previous invasive cancer, except for skin cancer (excluding melanoma) unless the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of the oral cavity or bladder)
12. Collagen or autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome)
13. Lymph node disease (N1)
14. Evidence of distant metastasis (M1)
15. Contraindication to systemic treatment
16. Pregnant women
17. Non-compliance with the dose limits established in the treatment plan