PROSPECTIVE: A study for people with early breast cancer to see whether surgery combined with MRI scans and other tests can identify people who may safely skip post-operative radiation therapy without increasing the chance of the cancer returning in the same breastA Two-arm, Non-randomised, Prospective, Multicentre Study Using Magnetic Resonance Imaging (MRI) Findings and Pathology Features to Select Patients With Early Breast Cancer for Omission of Post-operative Radiotherapy

Exclusion

Any one of the following at Registration is regarded as a criterion for exclusion from the study:

1. Triple negative breast cancer (ER-negative and PR-negative and HER2-negative) where ER and PR positivity is defined as ≥ 10% staining on IHC.
2. Previous invasive breast cancer and/or DCIS in either breast.
3. Prior RT to the breast or chest.
4. Participants who plan to have a mastectomy for the index cancer.
5. Lymphovascular invasion (LVI) reported on diagnostic core biopsy.
6. Multifocal/multicentric breast cancer on breast imaging before registration.
7. Distant metastasis at diagnosis.
8. Bilateral breast cancer
9. Known breast cancer predisposition gene mutation carriers (BRCA1, BRCA2, PALB2, CHEK2, ATM, CDK1, p53, BARD1, RAD51C, RAD51D, CDH1, STK11, PTEN).
10. Contraindication to breast MRI scanning.
11. Concurrent illness/conditions which limits life expectancy to 10 years or less.
12. Has moderate or marked BPE in the breast containing the index cancer (where MRI is done before registration).
13. Inability to give informed consent.

Allocation: Arm A - Radiotherapy Omission

In addition to the above criteria, for inclusion in the omission of radiation therapy arm of the study after surgery, participants must fulfil all the following criteria. Participants not fulfilling any one of the following criterial will be allocated to Arm B:

1. Has nil/minimal or mild BPE in the breast containing the index lesion on pre-operative breast MRI.

2. BCS with unifocal**, invasive primary tumour (including any surrounding DCIS) ≤ 20 mm.

   The overall tumour size (including additional foci of DCIS) must remain ≤ 20 mm. The tumour size is defined as the longest distance between the outer most edges of all foci, the space between the two or more foci is included in the overall size: Size = ('Focus A + Focus B + 'the distance between A and B').

3. Radial resection margins must be ≥ 2 mm clear of any invasive cancer and ≥ 2 mm clear of any DCIS. Superficial or deep margins of < 2 mm for invasive cancer and DCIS are allowed if there is no tumour on ink and all breast tissue from the subcutaneous tissue or pectoralis fascia respectively was removed and radial margins are ≥ 2 mm for invasive cancer and DCIS.
4. pN0 (pN0 i+ is eligible for inclusion) by sentinel node biopsy and/or axillary dissection.
5. Absence of LVI and extensive intraductal component (EIC) on final pathology.
6. The extent of invasive cancer is at least 50% of the total tumour size (invasive cancer + DCIS).
7. Have no additional BIRADS 3+ lesions not shown to be benign on pre-operative or surgical biopsy.
8. Participants with Grade 3 cancer and/or HER2-positive cancer must agree to comply with systemic treatment recommendations.

9. Participants must be allocated to a treatment arm within 8 weeks after final breast surgery.

   • Where histopathology is unable to identify a 'bridge' of tumour tissue joining two or more apparent invasive cancer foci the following will be used to confirm unifocal disease:

     • All foci must be of the same histological subtype
     • All foci must have the same hormone (ER and PR) and HER2 status.

Allocation: Arm B - Standard Treatment (ineligible for RT omission on study; includes management of MRI-detected lesions)

In addition to the above Inclusion Criteria, participants who fulfil one any of the following criteria will receive standard treatment:

1. Has moderate or marked BPE in the breast containing the index lesion on pre-operative breast MRI.
2. Has a biopsy-proven mOL identified on breast MRI.
3. Suspicious lesion identified on CEM but not on MRI and confirmed on investigation to be a DCIS or invasive breast cancer.
4. Surgical pathology does not meet the inclusion criteria. 2mm radial margins are required, as guidelines suggesting "no tumour on ink" relate to those receiving adjuvant RT.
5. Clinical team meeting determination that RT be recommended.
6. Participant chooses to have RT despite being eligible for RT omission.