Breast Re-irradiation After Second Ipsilateral Lumpectomy

Inclusion criteria

• Diagnosed with ER+HER2- breast cancer
• Provision of signed and dated ICF
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Age ≥ 40 years
• Oncotype \< 26 (postmenopausal) \<16 (premenopausal), Low, or Ultra-Low index.
• Minimum interval of 18 months from last breast radiotherapy session.
• Prior radiation therapy in the form of brachytherapy, external beam MV photons, protons or intraoperative radiation are allowed with an upper total dose limit of 68 Gy (EQD2) for those patients with prior records available.
• Ipsilateral recurrence, unifocal \< 3 cm with negative margins, N0, Tis and invasive (pathological staging)
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Planning target volume: whole breast (PTV: WB) ratio \< 1/2
• Life expectancy \> 12 months
• Individuals able to become pregnant: agreement to use highly effective contraception starting at screening through treatment, and for 1 year after the end of PBI. Should a participant become pregnant or suspect that they are pregnant while participating in this study, they should notify the treating physician immediately.
• A person able to become pregnant is any person assigned female at birth (regardless of gender identity, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has not had menses at any time during the preceding 12 consecutive months)

Exclusion criteria

• BRCA1/2 mutation or any other receptor subtypes
• Individuals assigned male at birth with breast cancer
• Pregnancy or breastfeeding
• Skin involvement
• Distant metastasis
• Patients with initial high-risk triple negative or HER-2 enriched breast cancer will be excluded from the trial. However, if the initial subtype is not known, patients will still be allowed to enroll, and the initial primary tumor information will be recorded as missing on the clinical forms.
• Other malignancies (except skin)
• Connective tissue disorder (e.g., scleroderma, lupus)
• Any other condition that may put a participant at higher risk, at the discretion of the investigator.