A Randomized Phase III Trial of the Value of Early Local Therapy for the Intact Primary Tumor in Patients With Metastatic Breast Cancer
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Breast Cancer
- Sponsor
- Eastern Cooperative Oncology Group
- Enrollment
- 390
- Locations
- 376
- Primary Endpoint
- 3-year Overall Survival Rate
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
RATIONALE: The primary tumor might be a source of re-seeding of distant sites and therefore elimination of this source of metastasizing cells by early local therapy may be of benefit.
PURPOSE: This randomized phase III trial is studying early surgery to see how well it works compared to standard palliative therapy in treating patients with stage IV breast cancer.
Detailed Description
OBJECTIVES: Primary * To evaluate whether early local therapy of intact primary disease in patients with Stage IV breast cancer whose disease does not progress during initial optimal systemic therapy, will result in prolonged survival, compared to patients who receive local therapy for palliation only. Secondary * To compare the time to uncontrolled chest wall disease between patients who receive early local therapy versus patients who receive palliative local therapy. * To determine whether there is a difference in health-related quality-of-life (HRQOL) between patients who receive early local therapy versus patients who receive palliative local therapy. * To determine whether the absolute value of circulating tumor cells (CTC) burden at 6 months following randomization (time +6) will be lower in the palliative therapy arm than in early local therapy arm, and whether this value is inversely related to survival (lower CTC, longer survival). Exploratory * To collect tumor and blood specimens for future exploration of the biological interactions between the primary tumor and metastatic lesions and the effect of primary tumor resection. OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor and treatment plan (ER+ or PR+, HER2-, endocrine therapy alone vs ER+ or PR+, and HER2-, chemotherapy and/or endocrine therapy vs ER- or PR-, and HER2- vs HER2+), and number of involved organ systems with distant disease (regional nodes in the axillary, supraclavicular, and internal mammary locations are not considered distant sites) (1 vs \> 1). Patients are randomized to 1 of 2 treatment arms in 1:1 ratio. * Arm I: Patients receive standard palliative therapy, if needed, to address symptoms such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a combination of both. * Arm II: Patients undergo surgery comprising breast-conserving therapy (BCT) or total mastectomy according to patient and treating physician preference. Surgery is to occur no later than 10 weeks after completion of 32 weeks of systemic therapy. Free surgical margins must be achieved with re-excision or mastectomy for patients undergoing BCT. After completion of BCT, patients undergo radiotherapy once a day, 5 days per week. Patients who had mastectomy undergo radiotherapy at the discretion of treating physician. Patients may undergo blood and tumor tissue sample collection for circulating tumor cells (CTC) burden and future studies. Patients complete the Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT- TOI) and FACT - General (22) and the Breast Cancer Subscale (FACT-B) quality-of-life questionnaires at baseline and periodically during study. After completion of study therapy, patients are followed up periodically for 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of intact primary (not recurrent) invasive carcinoma of the breast
- •Stage IV disease
- •Confirmation of the primary tumor should be by needle biopsy (preferred)
- •Incisional surgical biopsy allowed as long as there is residual palpable or tumor image in the breast
- •Patients must be judged to be candidates for complete resection with free margins followed by radiation therapy (if radiation therapy is indicated)
- •For women not undergoing axillary dissection, sentinel node biopsy should document an axillary nodal burden of 1-2 involved lymph nodes (i.e., ACOSOG Z-11 criteria may be applied)
- •Prior non-invasive (Ductal Carcinoma In Situ) cancer allowed provided there has been no recurrence
- •Prior ipsilateral invasive cancer allowed if more than 5 years previous
- •Patients should have at least one organ system involved with distant metastatic disease
- •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
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
3-year Overall Survival Rate
Time Frame: Assessed at baseline, then every 3 months within 2 years and every 6 months between 2-5 years, up to 5 years
Overall survival (OS) was defined as time from randomization to death from any cause. All patients will be followed for survival through 5 years. Cases with incomplete follow-up or without record of vital status will be censored at the date of last contact. 3-year OS rate was estimated using Kaplan-Meier method.
Secondary Outcomes
- 3-year Cumulative Incidence of Locoregional Recurrence/Progression(Assessed at baseline, then every 3 months within 2 years and every 6 months between 2-5 years, up to 5 years)
- Health-related Quality of Life (HRQL)(Assessed at 18 months after randomization)