Breast CancerPOSITIVE-BoneNCT07687225
Surgery vs. No Surgery for Primary Tumor in De Novo Stage IV Breast Cancer With Solitary Bone Metastases
A study testing Primary Tumor Resection and Standard systemic therapy in people with Breast Cancer and Stage IV Breast Cancer, run by West China Hospital.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer, Stage IV Breast Cancer, Bone Metastases
- What is being tested?
- Primary Tumor Resection and Standard systemic therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 216 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2026to 31 Dec 2036
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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.
Read the 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.
- Conditions
- Breast Cancer, Stage IV Breast Cancer, Bone Metastases
- Being tested
- Primary Tumor Resection, Standard systemic therapy
- Keywords
- Breast Cancer, Stage IV, Bone Metastasis
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Primary Tumor ResectionProcedure or surgery
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.
Standard systemic therapyOther
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 without immunotherapy (e.g., pembrolizumab) for triple-negative disease. All patients with bone metastases routinely receive bone-modifying agents (zoledronic acid or denosumab).
| Study group | Role | What they receive |
|---|---|---|
| Surgery Group | Experimental | Patients undergo primary tumor surgery (total mastectomy or breast-conserving surgery with sentinel lymph node biopsy or axillary lymph node dissection, with or without immediate breast reconstruction) within 4 weeks after randomization, followed by continued standard systemic therapy. Receives: Procedure: Primary Tumor Resection |
| Non-Surgery Group | Active comparator | Patients receive standard systemic therapy alone based on their molecular subtype (e.g., HR+/HER2-: endocrine therapy ± CDK4/6 inhibitor; HER2+: anti-HER2 therapy + chemotherapy; Triple-negative: chemotherapy ± immunotherapy). Palliative local therapy (e.g., radiotherapy) for bone metastases or for managing severe local complications from the primary tumor (e.g., uncontrolled ulceration, bleeding) is permitted but not elective curative-intent primary tumor surgery. Receives: Other: Standard systemic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Time from randomization to death from any cause.
Measured: 5 years post-randomization
Secondary outcomes (5)
Overall Survival (OS)
Time from randomization to death from any cause.
Measured: 3 and 10 years post-randomization
Progression-Free Survival (PFS)
Time from randomization to first documented disease progression (local progression, regional recurrence, or new/ progressive distant metastases) or death from any cause.
Measured: Up to 10 years post-randomization
Breast Cancer-Specific Survival (BCSS)
Time from randomization to death due to breast cancer.
Measured: Up to 10 years post-randomization
Patient-Reported Outcomes (PROs)
Quality of life measured by the EORTC QLQ-C30 (global health status/QoL).
Measured: Baseline, 6 months, 5 years, and 10 years post-randomization.
Patient-Reported Outcomes (PROs)
Quality of satisfaction measured by the BREAST-Q (psychosocial well-being, sexual well-being, and chest physical well-being) questionnaires.
Measured: Baseline, 6 months, 5 years, and 10 years post-randomization.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2031 (estimated)
- Study completion31 Dec 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by West China HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 216 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, The Nineth Hospital of Shenzhen, Longgang Center Hospital, Baotou Cancer Hospital, Hebei General Hospital, General Hospital of Ningxia Medical University, The First Hospital of Jilin University, Tangshan People's Hospital, Guangdong Women and Children Hospital, Nanchang Third Hospital, Cancer Hospital of Guangxi Medical University, Xinjiang Medical University Cancer Hospital, Anyang Tumor Hospital, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Shanxi Bethune Hospital, Hebei Medical University Fourth Hospital, The Affiliated Hospital of Qingdao University, Suzhou Municipal Hospital, Zhejiang Provincial People's Hospital, Hunan Cancer Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Shanxi Province Cancer Hospital, LanZhou University, Lanzhou University Second Hospital
- Responsible party
- Principal investigator, Du Zhenggui, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07687225
- Sponsor's protocol ID
- 2026(194)
- Acronym
- POSITIVE-Bone
- Status last verified
- Jun 2026
- First submitted
- 24 Jun 2026
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data via the request portal. All IPD requests should be emailed to Dr. Zhenggui Du, the general project leader, and will be evaluated by Dr. Du and the head of the collaborating organization to decide whether to approve.
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07687225
- Acronym / sponsor ID
- POSITIVE-Bone / 2026(194)
- Conditions
- Breast Cancer, Stage IV Breast Cancer, Bone Metastases
- Keywords
- Breast Cancer, Stage IV, Bone Metastasis
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 216 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Collaborators
- The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, The Nineth Hospital of Shenzhen, Longgang Center Hospital, Baotou Cancer Hospital, Hebei General Hospital, General Hospital of Ningxia Medical University, The First Hospital of Jilin University, Tangshan People's Hospital, Guangdong Women and Children Hospital, Nanchang Third Hospital, Cancer Hospital of Guangxi Medical University, Xinjiang Medical University Cancer Hospital, Anyang Tumor Hospital, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Shanxi Bethune Hospital, Hebei Medical University Fourth Hospital, The Affiliated Hospital of Qingdao University, Suzhou Municipal Hospital, Zhejiang Provincial People's Hospital, Hunan Cancer Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Shanxi Province Cancer Hospital, LanZhou University, Lanzhou University Second Hospital
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 1 Sep 2031 (estimated)
- Study completion
- 31 Dec 2036 (estimated)
- First posted
- 7 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Surgery Group | Experimental | Procedure: Primary Tumor ResectionPatients undergo primary tumor surgery (total mastectomy or breast-conserving surgery with sentinel lymph node biopsy or axillary lymph node dissection, with or without immediate breast reconstruction) within 4 weeks after randomization, followed by continued standard systemic therapy. |
| Non-Surgery Group | Active comparator | Other: Standard systemic therapyPatients receive standard systemic therapy alone based on their molecular subtype (e.g., HR+/HER2-: endocrine therapy ± CDK4/6 inhibitor; HER2+: anti-HER2 therapy + chemotherapy; Triple-negative: chemotherapy ± immunotherapy). Palliative local therapy (e.g., radiotherapy) for bone metastases or for managing severe local complications from the primary tumor (e.g., uncontrolled ulceration, bleeding) is permitted but not elective curative-intent primary tumor surgery. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Primary Tumor ResectionSurgical 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. | Procedure or surgery | Surgery Group |
| Standard systemic therapySystemic 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 without immunotherapy (e.g., pembrolizumab) for triple-negative disease. All patients with bone metastases routinely receive bone-modifying agents (zoledronic acid or denosumab). | Other | Non-Surgery Group |
Primary outcome
Overall Survival (OS)
Time frame: 5 years post-randomization
Time from randomization to death from any cause.
5 secondary outcomes
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data via the request portal. All IPD requests should be emailed to Dr. Zhenggui Du, the general project leader, and will be evaluated by Dr. Du and the head of the collaborating organization to decide whether to approve.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A study testing Primary Tumor Resection and Standard systemic therapy in people with Breast Cancer and Stage IV Breast Cancer, run by West China Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhenggui Du (+86 13880768222, docduzg@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: 5 years post-randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.