Surgery vs. No Surgery for Primary Tumor in De Novo Stage IV Breast Cancer With Solitary Bone Metastases

Official title

A National Multicenter, Prospective, Randomized Controlled Trial Comparing Primary Tumor Surgery Followed by Systemic Therapy With Systemic Therapy Alone in Patients With De Novo Stage IV Breast Cancer and Solitary Bone Metastases

Overview

This is a national multicenter, prospective, randomized controlled trial. The study aims to compare the 5-year overall survival (OS) between patients receiving primary tumor surgery followed by systemic therapy (surgery group) and those receiving systemic therapy alone (non-surgery group) in patients with de novo Stage IV breast cancer who have solitary bone metastases. Secondary objectives include comparing progression-free survival (PFS), breast cancer-specific survival (BCSS), local control rates, patient-reported outcomes (BREAST-Q, QLQ-C30), safety (surgical complications and systemic therapy toxicities), and cost-effectiveness.

Detailed description

The value of primary tumor resection in de novo stage IV breast cancer (BC) remains debated. While early retrospective studies suggested a potential survival benefit, recent large-scale randomized controlled trials (e.g., JCOG1017, E2108) have shown no OS benefit for the overall stage IV BC population. However, exploratory subgroup analyses consistently point towards a potential benefit for patients with hormone receptor-positive (HR+) disease and low metastatic burden, such as solitary bone metastases.

Given the unique biological behavior of HR+ BC and the effectiveness of modern systemic therapies (e.g., endocrine therapy + CDK4/6 inhibitors), it is hypothesized that primary tumor surgery may provide an additional "consolidation" benefit in this specific subgroup by improving local control and potentially prolonging survival. To address this, our team has designed this national multicenter, prospective, randomized controlled trial.

This study will enroll patients with de novo stage IV BC confirmed to have only bone metastases. All participants will receive standard systemic therapy based on their molecular subtype. Participants will be randomized 1:1 to either undergo primary tumor surgery (mastectomy or breast-conserving surgery with or without immediate reconstruction) within 4 weeks of randomization, followed by continued systemic therapy, or to receive systemic therapy alone. Palliative radiotherapy for bone metastases is permitted in both arms. The primary endpoint is 5-year overall survival. Secondary endpoints include PFS, BCSS, local control rate, quality of life (BREAST-Q, QLQ-C30), surgical complication rates, and cost analysis. This study will provide high-level evidence to guide personalized treatment decisions for this specific patient subgroup in China.

Interventions

• Procedure Primary Tumor Resection
  Surgical removal of the primary breast tumor. The procedure type (mastectomy or breast-conserving surgery) is determined by tumor size, location, and patient preference, and is performed by experienced breast surgeons following national guidelines. Axillary staging (sentinel node biopsy or dissection) is performed concurrently. Immediate breast reconstruction (prosthesis or autologous tissue) may be performed when indicated.
• Other Standard systemic therapy
  Systemic treatment administered according to the patient's molecular subtype (HR+, HER2+, or Triple-negative) based on Chinese and international clinical guidelines. Regimens include, but are not limited to, endocrine therapy (e.g., letrozole, exemestane) with or without CDK4/6 inhibitors (e.g., palbociclib) for HR+/HER2- disease; anti-HER2 targeted therapy (e.g., trastuzumab, pertuzumab) combined with chemotherapy for HER2+ disease; and chemotherapy (e.g., taxanes, anthracyclines) with or witho

Primary outcome measures

• Overall Survival (OS) [Time frame: 5 years post-randomization]

Secondary outcome measures (5)

• Overall Survival (OS) [Time frame: 3 and 10 years post-randomization]
• Progression-Free Survival (PFS) [Time frame: Up to 10 years post-randomization]
• Breast Cancer-Specific Survival (BCSS) [Time frame: Up to 10 years post-randomization]
• Patient-Reported Outcomes (PROs) [Time frame: Baseline, 6 months, 5 years, and 10 years post-randomization.]
• Patient-Reported Outcomes (PROs) [Time frame: Baseline, 6 months, 5 years, and 10 years post-randomization.]

Eligibility criteria

Inclusion criteria

• Female patients aged 18 to 70 years (inclusive);
• Histopathologically confirmed (by core needle biopsy) invasive breast cancer;
• Diagnosed with de novo Stage IV breast cancer with metastases confirmed to be limited to bone;
• Patients may be enrolled either at initial diagnosis or after receiving first-line systemic therapy;
• Willing and able to provide written informed consent.

Exclusion criteria

• Disease progression (per RECIST 1.1 criteria) in the primary tumor, regional lymph nodes, or bone metastases after first-line systemic therapy;
• Presence of other primary malignancies;
• Severe comorbidities that would preclude surgery or safe administration of systemic therapy (e.g., severe cardiopulmonary disease, uncontrolled diabetes, long-term smoking history with poor pulmonary function, immunodeficiency);
• Current participation in another clinical trial that would interfere with the outcomes of this study;
• Refusal to provide informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07687225 · 2026(194)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗