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SWOG 1007

A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients with 1-3 Positive Nodes, Hormone Receptor-Positive and HER-2 Negative Breast Cancer with Recurrence Score (RS) of 25 or Less

Eligibility Criteria

STEP 1 Oncotype DX Testing
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 non-amplified FISH for screening

Estrogen and progesterone positivity must be assessed according to ASCO/CAP guidelines (assays are considered positive if there are at least 1% positive nuclear staining.

HER-2 test result negativity must be assessed as per ASCO/CAP 2013 guidelines using IHC, ISH or both. HER-2 is negative if a single test performed in a tumor specimen shows: a) IHC negative (0 or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number < 4.0 signals per cell by single probe or HER-2/CEP ratio < 2.0 with an average copy number < 4.0 signals per cell by dual probe). If HER-2 IHC is 2+, evaluation for gene amplification (ISH) must be performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+. HER-2 equivocal is not eligible.

Patients with multifocal, multicentric, and/or synchronous bilateral breast cancers are allowed. 
Patients will have undergone axillary staging by sentinel node biopsy or axillary lymph node dissection (ALND).  Patients must have at least one, but no more than three known positive lymph nodes (pN1a, pN1b or pN1c). Patients with micrometastases as the only nodal involvement (pN1mi) are not eligible. Patients with positive sentinel node are not required to undergo full axillary lymph node dissection. This is at the discretion of the treating physician.
      
Axillary node evaluation is to be performed per the standard of care at each institution

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 or endocrine therapy). Radiation in the opposite breast is acceptable. Partial breast irradiation (including brachytherapy) is not allowed.

Patients must have had either breast-conserving surgery with planned radiation therapy or total mastectomy (with or without planned post mastectomy radiation).  Patients must have clear margins.

Registration of patients who have not yet undergone Oncotype DX® 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® 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® Breast Cancer Assay which will be performed according to the standard commercial process. 

If the Oncotype DX® 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® Recurrence Score is already known and is greater than 25, the patient is ineligible.

Patients must be female ≥ 18 years of age.  As the Oncotype DX® Recurrence Score has not been validated in men with breast cancer, men are not eligible for this study.

Patients must have a performance status of 0-2 by Zubrod criteria

Patients must be able to receive taxane and/or anthracycline based chemotherapy. 
Patients must not have begun chemotherapy or endocrine therapy for their breast cancer prior to registration.

Patients must not require chronic treatment with systemic steroids or other immunosuppressive agents. Inhaled steroids are allowed.

Patients must not have received an aromatase inhibitor (AI) or a selective estrogen receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to registration.

Patients must not be pregnant or nursing due to the possibility of harm to a fetus or nursing infant from this treatment regimen. Women of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.

No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease-free for 5 years.

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. 

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. 

Recurrence score (RS) by Oncotype DX® must be ≤ 25

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.

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.

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.

Treatment Plan


Step 1:  Tumor tissue is submitted for Oncotype DX testing.  Women with a Recurrence Score (RS) of 25 or less are eligible for Step 2.  Women whose Oncotype DX testing was done prior to enrolling in the study are still eligible, as long as the RS is 25 or less.

RS > 25:  Discuss appropriate treatment options with oncologist.  No further study procedures.
RS ≤ 25:  Discuss randomization to Step 2.  Patients may elect to proceed to Step 2 or be treated off study.

Step 2:  Patients are randomized to one of 2 arms.  Investigators can choose from an approved list of standard chemotherapy and hormonal therapy.

Arm 1:  Standard chemotherapy followed by hormonal (endocrine) therapy
Arm 2:  Hormonal (endocrine) therapy alone

No drugs are provided by the sponsor.