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

- • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.

- Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen. ** For patients with a T1a tumor (less than or equal to 0.5 cm in size) who do not already have an Oncotype DX Recurrence Score at study entry, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory.

- 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.

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

- Patients may be premenopausal or postmenopausal at the time of study entry. For study purposes, postmenopausal is defined as: Age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or a documented hysterectomy; or Age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or Documented bilateral oophorectomy.

- The interval between the last surgery for breast cancer (including re-excision of margins) and study entry must be no more than 70 days.

- The patient must have recovered from surgery with the incision completely healed and no signs of infection.

- Bilateral mammogram or MRI within 6 months prior to study entry. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Patients must be intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of endocrine therapy is at the treating physician's discretion.

- • Definitive clinical or radiologic evidence of metastatic disease.

- History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.

- 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. (Short course endocrine therapy of < 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18.)

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

- Prior breast or thoracic RT for any condition.

- Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.

- Pregnancy or lactation at the time of study entry or intention to become pregnant during treatment. (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to study entry.)

- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study therapy or that may affect the interpretation of the results or render the patient at high risk from treatment complications.

- Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.

- Use of any investigational product within 30 days prior to study entry.