Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
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.
Phase
Phase 3
Funding Agency/Sponsor
National Cooperative Group
Disease
Breast Cancer
Enrollment Eligibility
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. 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
examination.
- 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
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. (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) 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.
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. (Patients with multifocal carcinoma are
eligible.)
- 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, biotherapy, and/or endocrine
therapy administered for the currently diagnosed breast cancer prior to study
entry.
(Short course endocrine therapy of less than 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.)
- 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.