A Phase III Clinical Trial Evaluating De-Escalation of Breast Radiation for Conservative Treatment of Stage I, Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA)

Primary Outcome Measure:

• Time to invasive or noninvasive IBTR. [Time Frame: 5 years]
  • Time from randomization to any invasive or noninvasive IBTR or last follow-up (expressed as % IBTR-free)

Inclusion Criteria:

• 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.
  • The patient must have an ECOG performance status of 0 or 1.
  • 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. 
  • The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
  • Patient must have undergone axillary staging.
  • The following staging criteria must be met postoperatively according to AJCC 8th edition criteria: By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm). By pathologic evaluation, ipsilateral nodes must be pN0.
• 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. 
• 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. 
• 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.

Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease.
  • pT2 - pT4 tumors including inflammatory breast cancer.
  • Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
  • Patient had a mastectomy.
  • Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
  • Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
  • Non-epithelial breast malignancies such as sarcoma or lymphoma.
  • Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. 
  • Paget's disease of the nipple.
  • Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. 
  • Synchronous or previous contralateral invasive breast cancer or DCIS. 
  • Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. 
  • Treatment plan that includes regional nodal irradiation.
  • Any treatment with radiation therapy, chemotherapy, biotherapy, and/or endocrine therapy administered for the currently diagnosed breast cancer prior to study entry.
• 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.
• Patients intending to continue on oral, transdermal, or subdermal estrogen replacement 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.
• Other inclusion/exclusion criteria are present. Please contact the study team for a complete list.