Concept-verification Clinical Trial on the Inhibition of Breast Cancer Lung Metastasis Progression by Hyperbaric Oxygen

Breast cancer is prone to distant metastasis, with the lungs being one of the most common target sites. Tumor hypoxia (a low-oxygen microenvironment) is a key factor promoting tumor progression and metastasis, and it can also reduce the efficacy of conventional treatments. HBOT delivers 100% oxygen at a pressure of 2.0-2.5 atmospheres absolute, which effectively improves tissue oxygenation, modifies the tumor microenvironment, and may suppress tumor growth by inhibiting cell migration and invasion and inducing tumor cell death.

This study aims to verify the potential of HBOT as an adjuvant therapy to slow or block breast cancer lung metastasis progression. Eligible participants (aged 18-75 years with pathologically confirmed breast cancer accompanied by lung metastasis and no prior HBOT contraindications) will receive standard breast cancer treatment (including surgery, chemotherapy, radiotherapy, or targeted therapy as appropriate) combined with HBOT. The HBOT regimen will consist of 6 sessions per week for 2 consecutive weeks, with each session lasting 120 minutes, including 15 minutes for increasing pressure and 15 minutes for reducing pressure, at 2.5 ATA and 100% oxygen. Over a 6-month follow-up period, participants will undergo regular assessments including chest CT (to monitor lung metastasis lesions), serum tumor marker tests, and quality of life evaluations. The primary outcome is the objective response rate (ORR) of tumors evaluated according to the RECIST version 1.1 criteria: the proportion of subjects with complete response (CR) + partial response (PR), and secondary outcomes include changes in progression-free survival, the number and viability of circulating tumor cells and safety indicators.

Participants may benefit from potential inhibition of lung metastasis progression and access to a well-tolerated adjuvant therapy. HBOT-related side effects are usually mild and temporary, such as ear discomfort or pressure changes, which will be closely monitored and managed by the study team throughout the treatment process.

This research is significant as it explores a clinically available, safe therapy for addressing breast cancer lung metastasis-a major challenge affecting patient prognosis. If proven effective, HBOT could become an important part of comprehensive breast cancer treatment, helping to improve patient outcomes and quality of life.

• Hyperbaric Oxygen Therapy (Device), also known as Hyperbaric Oxygen Therapy (2.5 ATA and 100% oxygen): The HBOT regimen will consist of 6 sessions per week for 2 consecutive weeks, with each session lasting 90 minutes at 2.5 ATA and 100% oxygen.

Primary outcomes

• Objective Response Rate [From the time of registration to 6 weeks after the end of treatment (that is, at 8 weeks)]: The objective response rate (ORR) of lung metastatic tumors as assessed according to the RECIST 1.1 standard: the proportion of subjects who achieved complete response (CR) or partial response (PR).

Secondary outcomes

• Disease Control Rate (DCR) [Up to 24 weeks]: Disease Control Rate (DCR): The proportion of subjects who achieved Complete Response (CR), Partial Response (PR), or Stable Disease (SD)
• Progression-Free Survival [The period of time from the date of patient enrollment until any recorded tumor progression or death due to any cause. Up to 52 weeks]: Progression-Free Survival
• CTC Number and Viability [From enrollment to the end of treatment at 2 weeks]: Number and viability changes of circulating tumor cell in blood samples between before and after treatment
• Adverse Events [From enrollment to the end of the trial. Up to 24 weeks]: The incidence, severity and outcome of adverse events during treatment will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0) of the National Cancer Institute of the United States.

Sex: Female, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Aged 18-75 years, female;
2. Histologically confirmed invasive breast cancer with lung metastasis (diagnosed via contrast-enhanced chest CT, PET-CT, or MRI);
3. Disease progression after at least 1 line of systemic therapy containing chemotherapy for recurrent/metastatic disease (per RECIST 1.1 criteria);
4. At least one measurable lung metastatic lesion (≥10 mm on spiral CT/MRI, not previously treated with radiotherapy) per RECIST 1.1;
5. Adequate organ function (e.g., hemoglobin ≥90 g/L, alanine transaminase/aspartate transaminase ≤3× upper limit of normal \[ULN\], serum creatinine ≤1× ULN, no severe arrhythmia or myocardial ischemia on ECG);
6. ECOG performance status ≤2 and life expectancy ≥3 months;
7. Use of medically approved contraception (for women of childbearing potential) during treatment and for at least 3 months after the last treatment;
8. Voluntary participation, signed informed consent, and willingness to comply with treatment and follow-up.

Exclusion Criteria:

1. Received radiotherapy (excluding palliative radiotherapy) within 3 weeks prior to treatment; received major surgery (excluding minor outpatient procedures such as vascular access placement) within 3 weeks before the first cycle of study treatment;
2. Persistent grade ≥2 adverse events from prior treatments (e.g., chemotherapy, surgery) (except alopecia or conditions the investigator deems should not result in exclusion);
3. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina pectoris, myocardial infarction within the past 6 months, or ventricular arrhythmias;
4. Presence of third-space fluid accumulation that cannot be controlled by drainage or other methods;
5. Active HBV or HCV infection (HBV DNA ≥500 IU/ml or positive HCV RNA) with abnormal liver function;
6. Currently pregnant or breastfeeding;
7. Allergic diathesis, or known history of allergy to components of the conventional treatment medications in this study, or to HBOT-related equipment/gas components (e.g., pure oxygen);
8. Presence of contraindications to HBOT, such as untreated pneumothorax, pulmonary bullae, severe emphysema, history of epilepsy (with seizures within the past 2 years), or acute exacerbation of severe sinusitis/otitis media.