I. To determine the effect of endocrine therapy with versus without chemotherapy in patients with node-positive breast cancer who do not have high Recurrence Scores (RS) by Oncotype DX.
I. To compare overall survival (OS), distant disease-free survival (DDFS), and local disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS. II. To compare the toxicity across the treatment arms. III. To perform other assays or tests (in particular the PAM50 risk of relapse score) as they are developed and validated that measure potential benefit of chemotherapy and compare them to Oncotype DX.
IV. To determine the impact of management with Oncotype DX on patient-reported anxiety (co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after disclosure of test results, and during the randomized trial.
V. To determine the impact of Oncotype DX on the initial management cost of node-positive, HR-positive, HER2-negative breast cancer.
VI. To compare patient-reported utilities (e.g., QOL) for those randomized to chemotherapy versus no chemotherapy.
VII. To estimate the cost-effectiveness of management with Oncotype DX vs usual care using modeling and DFS information from the trial.
VIII. To determine the role of other assays (e.g., PAM50) as predictors of DFS, DDFS, and LDFI of patients randomized to chemotherapy versus no chemotherapy.
IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on patient-reported fatigue and cognitive concerns (secondary HRQL outcomes).
X. To determine the impact of management with Oncotype DX on patient-reported decision conflict, perceptions regarding Oncotype DX testing, and survivor concerns prior to screening, after disclosure of test results, and during the randomized trial (secondary HRQL outcomes).
OUTLINE: This is a multicenter study. Patients are stratified according to Recurrence Score (0-13 vs 14-25), menopausal status (pre-menopausal vs post-menopausal), and type of nodal dissection (axillary lymph node dissection [with or without sentinel node mapping] vs sentinel node biopsy without axillary lymph node dissection). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity.
Patients may complete health-related quality-of-life (QOL) questionnaires at baseline and periodically during study. Information on Medicare and/or insurance coverage and on health coverage decisions may also be collected periodically.
After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for at least 15 years.
- Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes) invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2, as determined by IHC or gene amplification evaluation (e.g. FISH, CISH, etc.); estrogen and progesterone receptor positivity must be assessed according to ASCO/CAP guidelines as either ER or PR >= 1% positive nuclear staining; if HER2 IHC is 2+, an evaluation for gene amplification must be performed and must not be amplified, but otherwise gene amplification evaluation is not required if IHC is 0 or 1+ by institutional standards
- Patients must not have inflammatory breast cancer and must not have metastatic disease; patients with a prior diagnosis of DCIS are eligible if they received mastectomy alone (no therapeutic radiation, intraoperative radiation, or endocrine therapy); radiation in the opposite breast is acceptable
- Must have had breast-conserving surgery with planned radiotherapy or total mastectomy (with or without planned post mastectomy radiation) with clear margins within the past 28-84 days
- Menopausal status: pre- or post-menopausal
- Zubrod performance status 0-2
- Not pregnant or nursing
- Fertile patients must use an effective non-hormonal contraception method while on treatment and for ≥ 3 months after completion of protocol treatment
- No other prior malignancy except adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated stage 0, I, or II cancer from which the patient is currently in complete remission; or any other cancer from which the patient has been disease-free for the past 5 years
- LVEF ≥ 50% if an anthracycline-based regimen is planned
- Patients randomized to chemotherapy may also co-enroll in Phase III trials that compare chemotherapies
- No prior chemotherapy or endocrine therapy for breast cancer
- No prior preventive tamoxifen or raloxifene
- No prior therapeutic breast radiotherapy
- Not requiring concurrent chronic treatment with systemic steroids or other immunosuppressive agents
- Patients randomized to either arm may also co-enroll in Phase III trials that compare local therapies or compare systemic therapies (not including chemotherapy)
- Patients with multifocal, multicentric and synchronous bilateral breast cancers are allowed
- Multifocal disease is defined as more than one invasive cancer < 2 cm from the largest lesion within the same breast quadrant; (NOTE: The Oncotype DX testing must be completed on the largest lesion)
- Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the largest lesion within the same breast quadrant or more than one lesion in different quadrants; (NOTE: Oncotype DX testing should be completed on all tumors and the determination for eligibility should be made on the highest recurrence score)
- Synchronous bilateral disease is defined as invasive breast cancer with positive lymph nodes (axillary or intramammary) in at least one breast, diagnosed within 30 days of each other; (NOTE: The Oncotype DX testing should be completed on both tumors and the tumor with the highest recurrence score should be used)
- Patients must be able to receive taxane and/or anthracycline based chemotherapy
- The Quality of Life and Economic Substudy is permanently closed to accrual effective 12/1/12; patients who are able to complete a questionnaire in English must be offered the opportunity to participate in the Quality of Life and Economic Substudy. (The Quality of Life and Economic Substudy is available to U.S. INSTITUTIONS ONLY); patients who are not able to complete a questionnaire in English are registered to S1007 without participating in the Quality of Life and Economic Substudy
- Patients who consent to participate in the Quality of Life and Economic Substudy and who do not yet know the results of their Oncotype DX screening must agree to complete the S1007 Health-Related Quality of Life Questionnaire: Enrollment between 14 days prior to and 7 days after Step 1 Registration
- Patients who consent to participate in the Quality of Life and Economic Substudy and who do already know their Oncotype DX Recurrence Score (and it is 25 or less) will proceed to Step 2 Registration without completing the S1007 Health-Related Quality of Life Questionnaire Enrollment Form (but will complete the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form)
- Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines; for Step 1 registration of patients who have not yet submitted specimens for the Oncotype DX Breast Cancer Assay, the appropriate consent form is the Step 1 Consent Form; for both Step 1 and Step 2 registration of patients whose Recurrence Score is already known and is 25 or less, the appropriate consent form is the Step 2 Consent Form
Last updated: 04/01/2013
NCT ID: NCT01272037