S1007: Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/-Chemotherapy in Patients with 1-3 Positive Nodes, Hormone Receptor-Positive and HER2-Negative Breast Cancer with Recurrence Score (RS) of 25 or Less. RxPONDER: A Clinical Trial Rx for Positive Node, Endocrine Responsive Breast Cancer

Summary

this trial will use the regimens that have proven to be of greater benefit than earlier chemotherapy regimens in modern randomized trials. The study will use a simple parallel two-group randomization to chemotherapy followed by endocrine therapy or endocrine therapy alone in a lower risk, 1-3 node-positive population (identified by intermediate or low Recurrence Score) to determine if modern chemotherapy is efficacious and to identify those patients who will
benefit from the addition of chemotherapy.

Participant Eligibility

-->If patient has previously been tested by Oncotype DX(RegisteredTM), then she still must satisfy these eligibility criteria to be considered for randomization.
a. 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.
b. 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(RegisteredTM) 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(RegisteredTM) 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(RegisteredTM) testing should be completed on both tumors and the tumor with the highest
recurrence score should be used.)
c. Patients will have undergone axillary staging by sentinel node biopsy or axillary lymph nodes dissection (ALND). Patients must have at least one, but no more than three known positive lymph nodes (pN1mi, pN1a, pN1b or pN1c),
Patients with positive sentinel node are not required to undergo full axillary lymph node dissection.
( at the discretion of the treating physician)

Axillary node evaluation is to be performed per the standard of care at each institution
d. 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.
e. Patients must have had either breast-conserving surgery with planned radiation therapy or total mastectomy (with or without planned postmastectomy radiation).
Patients must have clear margins (as per local institutional guidelines).
f. Registration of patients who have not yet undergone Oncotype DX(RegisteredTM) screening must occur no later than 56 days after definitive surgery.
(For all patients, Step 2 Registration must occur within 84 days after definitive surgery.) If the Oncotype DX(RegisteredTM) Breast Cancer Assay has not been performed, patients must be willing to submit tissue samples for testing to determine the Recurrence Score value. A representative block or unstained sections from the representative block are sent directly to Genomic Health for Oncotype DX(RegisteredTM) Breast Cancer Assay which will be performed according to the standard commercial process

If the Oncotype DX(RegisteredTM) Recurrence Score is already known and is 25 or less, the patient must be registered to Step 2 immediately following Step 1 registration. If the Oncotype DX(RegisteredTM) Recurrence Score is already known and is greater than 25, the patient is ineligible.
g. Patients must be females >= 18 years of age. As the Oncotype DX(RegisteredTM) Recurrence Score has not been validated in men with breast cancer, men are not eligible for this study.
h. Patients must have a performance status of 0-2 by Zubrod criteria
i. Patients must be able to receive taxane and/or anthracycline based chemotherapy.


o. The Quality of Life and Economic Substudy is permanently closed to accrual effective 12/1/12. p. 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(RegisteredTM) 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.
q. As a part of the OPEN registration process (see Section 13.4 for OPEN access
instructions) the treating institution's identity is provided in order to ensure that
the current (within 365 days) date of institutional review board approval for this
study has been entered in the system.
5.2 STEP 2 REGISTRATION (Randomization)
The following additional criteria must be met in order for a patient to be considered
eligible for registration to the randomized trial. For each criterion requiring test results
and dates, please record this information on the S1007 Prestudy Form-Randomized
Study and submit to the Data Operations Center in Seattle (see Section 14.0). Any
potential eligibility issues should be addressed to the Data Operations Center in Seattle
at 206/652-2267 prior to registration.
a. Recurrence score (RS) by Oncotype DX(RegisteredTM) must be <= 25.
b. Step 2 Registration must take place within 84 days after definitive surgery.
Patients must not have begun chemotherapy or endocrine therapy for their
breast cancer prior to randomization.
c. 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 randomized to chemotherapy may also co-enroll in
Phase III trials that compare chemotherapies.
d. The Quality of Life and Economic Substudy is permanently closed to
accrual effective 12/1/12. Patients at U.S. INSTITUTIONS who consent to
participate in the Quality of Life and Economic Substudy must agree to complete
the S1007 Health-Related Quality of Life Questionnaire: Randomized Study
Form after Recurrence Score results and randomized treatment status are known
but before treatment has been initiated.
e. 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 all patients
the appropriate consent form for this registration is the Step 2 Consent Form.