Protocol e2108 is designed to examine the value of early local therapy for the primary tumor in arm B versus standard of care in arm a. Laboratory measurements that involve comparison of pre and post local therapy values can therefore only be performed in arm B. Howevere, teh Circulating Tumor Cell (CTC) burden prior to primary site local therapy may be substantially reduced by the preceding induction systemic therapy. Statistical testing of CTC values pre and post local therapy in arm B may therefore not be feasible. a more robust comparison would be one performed at six months following randomization, where local therapy would be completed in arm B and the CTC burden would represent the cumulative effects of local and systemic therapy (arm B) versus systemic therapy alone (arm a).
Registration (STEP 1)
1. Patients (male or female) must be older than 18 years and must have an intact primary (not recurrent) invasive carcinoma of the breast. Biopsy confirmation of the primary tumor should be by needle biopsy (preferred); incisional surgical biopsy is allowed as long as there is residual palpable or imageable tumor in the breast.
2. Patients with synchronous contralateral invasive breast cancer are excluded.
3. Patients should have at least one organ system involved with distant metastatic disease. If only a single metastatic lesion is present, biopsy is mandatory.
4. Baseline studies must be performed 8 weeks prior to the start of systemic therapy, and must document the extent of disease in the breast; the specifics of this are at physician discretion, but must address clinical signs and symptoms (see Section 7.1). If pre-therapy scans were not performed, scans performed within the first 4 weeks of systemic therapy, but prior to registration, will be accepted. Radiology reports documenting status of disease must be available.
5. If palliative radiation to non-breast sites is required prior to initiation of systemic therapy, scans may be completed within 8 weeks prior to or 4 weeks following the start of radiation therapy.
6. If patient has only one metastatic lesion/focus, this must be proven by biopsy and the pathology report confirming the diagnosis of primary breast cancer, as well as the metastatic site, must be available.
7. Patients may have had prior non-invasive (DCIS) cancer if there has been no recurrence; prior ipsilateral invasive cancer also allowed if more than 5 years previous.
8. Patients with a history of other primary cancers are eligible if the pathology report confirming the diagnosis of primary breast cancer is available and the other primary cancer was curatively treated with a 5-year disease-free interval. Patients with non-melanoma skin cancer are eligible;
however, patients with squamos cell carcinoma of other sites (except in-situ cervix) are not eligible.
9. Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception.
10. Patients with CNS metastases are eligible (as long as projected survival is > 6 months).
11. Patients who require radiotherapy to distant metastases during induction systemic therapy are eligible.
3.2 Randomization (STEP 2)
1. Date of randomization must be within 32 weeks of initiation of optimal systemic therapy.
2. Patients must have completed at least 16 weeks of optimal systemic therapy (appropriate to the tumor biological profile and the patient[Single Quote]s age and menopausal status). Note- The patient will be considered eligible if the last day of the treatment cycle meets the 16 weeks criteria. For example, the last chemotherapy dose might be administered in week 15, while the cycle might end in week 16 or 17. In this case, the patient will be considered eligible for the study.
If systemic therapy is discontinued for toxicity, there is no distant progression and at least 12 weeks of therapy have been delivered, then the patient remains eligible. If systemic therapy is changed for reasons other than progression of disease (e.g. from chemotherapy to endocrine therapy), the patient remains eligible.
3. Documentation regarding the details of administration of all systemic chemotherapy
must be available.
4. Patients must not have experienced distant disease progression since the start of systemic therapy, as evidenced by clinical and radiographic documentation of disease status before treatment and within 6 weeks prior to randomization, including:
a. No new sites of disease
b. No enlargement of existing sites by 20% or more in longest diameter
c. No symptomatic deterioration
d. Imaging at step 2 should preferably be the same as at Step 1 (baseline). It must address all previous sites of disease and all clinical signs and symptoms. If all Step 1 imaging tests cannot be repeated, the reason should be documented (e.g. declined by insurance). Step 2 imaging must evaluate all known sites of disease and address all signs/symptoms present at Step 2.
5. Patients must be judged to be candidates for complete resection with free margins followed by radiation therapy (if radiation therapy is indicated).
6. Local disease at the primary site must be asymptomatic.
7. Patients must have adequate organ function to undergo local therapy 4 weeks +/ - 2 weeks prior to randomization per investigator discretion and institutional guidelines.
8. Women must not be pregnant or breast-feeding due to toxicity of systemic therapy and radiotherapy to fetus/infant.
All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy.