De-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA)

Required: ESR1 positive (>=1% ER staining by IHC)

The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive.

Required: PR (PGR) positive (>=1% PgR staining by IHC)

The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive.

Required: HER2 (ERBB2) wild-type

The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.

Required: NONE Oncotype DX Recurrence Score <= 18 (Recurrence Score <= 18)

Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen.

Required: NONE MammaPrint Low (Low)

for a patient whose tumor has already had a MammaPrint test completed as part of usual care when being considered for enrollment and is in the binary "Low" category will meet this eligibility criteria and an Oncotype RS does not need to be performed.

Must have received: lumpectomy

The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist.

Must have received: axillary staging (sentinel node biopsy and/or axillary node dissection)

Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).

Cannot have received: mastectomy

Patient had a mastectomy.

Cannot have received: radiation therapy

Any treatment with radiation therapy, chemotherapy, or biotherapy, administered for the currently diagnosed breast cancer prior to pre-entry/Step 1.

Cannot have received: chemotherapy

Any treatment with radiation therapy, chemotherapy, or biotherapy, administered for the currently diagnosed breast cancer prior to pre-entry/Step 1.

Cannot have received: biotherapy

Any treatment with radiation therapy, chemotherapy, or biotherapy, administered for the currently diagnosed breast cancer prior to pre-entry/Step 1.

Cannot have received: endocrine therapy (raloxifene, tamoxifen, other selective estrogen receptor modulators (SERMs))

Exception: short course of preoperative endocrine therapy of less than 6 weeks duration (prior to randomization/Step 2) for this diagnosis after the core biopsy (and can continue postoperatively if: the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18, AND the patient had not initiated endocrine therapy prior to core biopsy tissue collection)

Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention.

Cannot have received: estrogen replacement (oral estrogen, transdermal estrogen, subdermal estrogen)

Exception: Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior to registration are eligible.

Patients intending to continue on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible.

Cannot have received: breast or thoracic radiation therapy

Prior breast or thoracic RT for any condition.