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De-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA)
Trial ID: NCT04852887
This Phase III Trial evaluates whether breast conservation surgery and endocrine therapy results in a non-inferior rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation with breast radiation and endocrine therapy.
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
- • The patient or a legally authorized representative must provide study-specific
informed consent prior to pre-entry/Step 1 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. If pathologic
examination demonstrates tumor at the line of resection, additional excisions may
be performed to obtain clear margins. (Patients with margins positive for LCIS
are eligible without additional resection.)
- The tumor must be unilateral invasive adenocarcinoma of the breast on histologic
- Patient must have undergone axillary staging (sentinel node biopsy and/or
axillary node dissection).
- The following staging criteria must be met postoperatively according to AJCC 8th
- By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm).
- By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with
pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible.)
- 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) or
patients at Canadian provinces or approved international sites where Oncotype DX
Recurrence Score testing would not be covered, who do not already have an
Oncotype DX Recurrence Score at pre-entry/Step 1, a specimen (unstained blocks or
slides) must be sent to the Genomic Health centralized laboratory. Tumor size
sample must be greater than or equal to 0.2 cm for analysis.
*** The Oncotype RS can be run on the biopsy core or surgical specimen. The
patient cannot have initiated endocrine therapy prior to tissue collection.
- An Oncotype RS is required for eligibility, however, 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.
- 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
- The tumor must have been determined to be HER2-negative by current ASCO/CAP
- Patients may be premenopausal or postmenopausal at the time of pre-entry/Step 1.
For study purposes, postmenopausal is defined as:
- Age 56 or older with no spontaneous menses for at least 12 months prior to
pre-entry/Step 1; or a documented hysterectomy; or
- Age 55 or younger with no spontaneous menses for at least 12 months prior to
pre-entry/Step 1 (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 pre-entry/Step 1 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 pre-entry/Step 1.
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.
- pT1 mi and 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. (Patients with multifocal carcinoma are
- 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. (Patients with synchronous or
previous ipsilateral LCIS are eligible.)
- Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients
with synchronous and/or previous contralateral LCIS are eligible.)
- Surgical margins that cannot be microscopically assessed or are positive at
pathologic evaluation. (If surgical margins are rendered free of disease by re-
excision, the patient is eligible.)
- Treatment plan that includes regional nodal irradiation.
- Any treatment with radiation therapy, chemotherapy, or biotherapy, administered
for the currently diagnosed breast cancer prior to pre-entry/Step 1.
- 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 pre-entry/Step 1.
- 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 are eligible for BR007 if they receive a 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
*** This does not apply to adjuvant endocrine therapy recommended for this
diagnosis which may start any time after surgery including prior to registration
- 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
- Pregnancy or lactation at the time of pre-entry/Step 1 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 pre-entry/Step 1.)
- 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
- 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 pre-entry/Step 1.
other: Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)
drug: Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)