Regional Radiotherapy in Biomarker Low Risk Node Positive Breast Cancer

Women with node positive breast cancer normally will receive endocrine therapy and some may
receive chemotherapy to help prevent the cancer from coming back. Many women will also
receive radiotherapy to the whole breast/chest area and the surrounding lymph glands (called
regional radiotherapy). No one really knows whether patients with low risk breast cancer need
to receive regional radiotherapy. Some women may be getting regional radiotherapy who do not
need it. These women may be exposed to the side effects of their treatment without benefit.

Inclusion Criteria:

- Patients must have newly diagnosed histologically proven invasive carcinoma of the
breast with no evidence of metastases.

- Patients must have been treated by BCS or mastectomy.

- Patients treated by BCS or mastectomy and axillary dissection must have 1-3 positive
axillary nodes (macrometastases, > 2 mm).

- Patients treated by BCS and SLNB alone must have only 1-2 positive axillary nodes
(macrometastases, > 2 mm).

- Patients treated by mastectomy and SLNB alone must have only 1 positive axillary node
(macrometastases, > 2 mm).

- Patients must be ER ≥ 1% and HER2 negative on local testing

- Patients must have an Oncotype DX recurrence score <18

- Patient must consent to provision of, and investigator(s) must confirm access to and
agree to submit to the CCTG Central Tumour Bank, a representative formalin fixed
paraffin block of tumour tissue in order that the specific correlative marker assays
described in the protocol may be conducted

- Patient must consent to provision of samples of blood in order that the specific
correlative marker assays described in the protocol may be conducted.

- Patients must have had endocrine therapy initiated or planned for ≥ 5 years. Endocrine
therapy can be given concurrently or following RT.

- Patients may or may not have had adjuvant chemotherapy.

- RT must be administered within 12 weeks of definitive surgery if the patient is not
treated with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 2-8
weeks after the last dose.

- Patient's ECOG performance status must be 0, 1 or 2.

- Patient's age must be ≥ 40 years.

- Patient's life expectancy is ≥10 years

- For the first 736 eligible English or French-speaking subjects who have agreed to
optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and
willing to complete the quality of life, health utilities and lost productivity
questionnaires in either English or French

- Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements

- Patients must be accessible for treatment and follow-up. Investigators must assure
themselves the patients randomized on this trial will be available for complete
documentation of the treatment, adverse events, and follow-up.

- In accordance with CCTG policy, protocol treatment is to begin within 3 weeks of
patient randomization.

- Women of childbearing potential must have agreed to use an effective contraceptive
method. A woman is considered to be of "childbearing potential" if she has had menses
at any time in the preceding 12 consecutive months.

Exclusion Criteria:

- Patients with nodal disease limited to micrometastases (pN1Mi, > 0.2 mm and ≤ 2 mm) or
isolated tumour cells (pN0i+ < 0.2 mm).

- Any prior history, not including the index cancer, of ipsilateral invasive breast
cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous
or previous ipsilateral LCIS are eligible.)

- Synchronous or previous contralateral invasive breast cancer. (Patients with
contralateral DCIS not treated with radiation are eligible.)

- History of non-breast malignancies except adequately treated non-melanoma skin
cancers, in situ cancers treated by local excision or other cancers curatively treated
with no evidence of disease for ≥ 5 years.

- Patients with pT3 or pT4 disease.

- Patients who are pregnant.

- Patients that have had prior ipsilateral chestwall/thoracic radiation.

- Patients treated with neoadjuvant chemo or endocrine therapy for breast cancer.

- Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.)
which would preclude RT.

- Patients with any serious active or co-morbid medical conditions, laboratory
abnormality, psychiatric illness, active or uncontrolled infections, or serious
illnesses or medical conditions that would prevent the patient from participating or
to be managed according to the protocol (according to investigator's decision).