Breast Cancer, Myocardial Injury After Noncardiac Surgery (MINS)
Conditions
Keywords
Propranolol, Breast Cancer Surgery, Beta-blockers, Tumor Microenvironment, Pragmatic Clinical Trial
Brief summary
This study aims to evaluate the impact of using propranolol, a non-selective beta-blocker, on preventing myocardial injury after non-cardiac surgery (MINS) in breast cancer patients who also have hypertension or angina. Stress from surgery and anesthesia can increase sympathetic activity and inflammation, which may lead to heart stress. This pragmatic clinical trial will compare patients who are prescribed propranolol as part of their routine care with those who are not. Researchers will analyze blood samples and surgical tissues collected during normal treatment to observe changes in heart health and the tumor microenvironment.
Detailed description
Breast cancer is the most common malignancy among women in Korea. Perioperative stress and acute physiological stimuli from surgery and anesthesia increase catecholamine secretion, which can lead to Myocardial Injury after Non-cardiac Surgery (MINS). Propranolol is known to stabilize hemodynamic variability by inhibiting sympathetic surge and reducing myocardial oxygen consumption. Recent studies also suggest that beta-blockers may influence the tumor microenvironment (TME) by reducing inflammation and regulating immune cell composition.This prospective, randomized, open-label, single-center pragmatic clinical trial will enroll 100 female patients (aged 20-70) with stage I-III breast cancer and comorbid hypertension or angina. Participants will be randomized 1:1 into two groups: 1. Propranolol Group: Patients receive propranolol for at least 14 days before surgery. 2. Non-Propranolol Group: Patients receive usual care without propranolol.The primary objective is to compare the incidence of MINS based on high-sensitivity Troponin T (hs-TnT) levels measured postoperatively. Exploratory objectives include analyzing markers of inflammation (CRP, LDH), tumor proliferation (Ki-67), and tumor-infiltrating lymphocytes (TILs) using blood and tissue samples naturally obtained during the clinical process. Long-term follow-up will be conducted for up to 5 years to evaluate recurrence and survival outcomes.
Interventions
DRUGpropranolol
Propranolol (dosage based on clinical indication) for at least 14 days before surgery until the morning of the operation.
OTHERUsual Care
Standard medical management (e.g., CCB, ACEi, ARB, or diuretics) at the physician's discretion, excluding beta-blockers.
Sponsors
Chang-Ik Yoon
Seoul St. Mary's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This is a prospective, randomized, open-label, two-arm, single-center pragmatic clinical trial. Eligible patients are randomized in a 1:1 ratio into either the Propranolol group or the Non-propranolol group, stratified by cancer stage (Stage 1 vs. Stage 2/3). The study evaluates the real-world clinical impact of preoperative propranolol administration on postoperative myocardial injury.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Female patients aged 20 to 70 years. 2. Patients diagnosed with hypertension or angina who require medication. 3. Patients diagnosed with unilateral, resectable primary breast cancer (ICD-10: C50), Stage I-III. 4. ECOG performance status of 0-1. 5. Patients scheduled to receive standard postoperative treatment (including adjuvant radiotherapy 6. Patients who voluntarily decide to participate and sign the written informed consent form
Exclusion criteria
1. Patients with distant metastases. 2. Patients with active infectious diseases, autoimmune diseases (including specific rheumatic diseases), coagulation disorders, or cardiovascular diseases other than hypertension or angina pectoris. 3. Patients with clinically significant hepatic, hematologic, or renal dysfunction, defined as any of the following: ① ANC \<1,500/mm3 * Platelets \<100,000/mm3 * Hb \<9 g/dL * AST and ALT \> 2.5 x upper limit of normal (ULN) ⑤ Alkaline phosphatase \> 2.5 x ULN ⑥ Total bilirubin \> 1 x ULN ⑦ Serum creatinine \>1.5 x ULN or estimated creatinine clearance \< 60 mL/min (as calculated using the method standard for the institution) 4. Patients with moderate to severe asthma or chronic obstructive pulmonary disease (COPD). 5. Patients who are pregnant or breastfeeding at the time of enrollment. 6. Patients with a history of malignancy within the past 5 years. 7. Patients for whom data collection is considered difficult at the discretion of the investigator. 8. Patients who are unable to understand or complete study questionnaires. 9. Patients who have received β-blockers within 30 days prior to screening. 10. Patients with systolic blood pressure \< 100 mmHg or heart rate \< 55 beats per minute.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Myocardial Injury after Noncardiac Surgery (MINS) | From the day of surgery (Day 0) up to 30 days postoperatively | MINS is defined as an elevated high-sensitivity cardiac Troponin T (hs-TnT) level measured for clinical purposes after surgery that exceeds the 99th percentile upper reference limit. Specifically, it is defined as: 1. 0.02-0.065 ng/mL with an absolute change of more than 0.005ng/mL or 2. any elevation ≥0.065 ng/mL or any absolute change more than 0.014 ng/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Perioperative Hemodynamic Stability: Systolic Blood Pressure Fluctuation | During surgery and in the recovery room (up to 2hours post-surgery)(Day 0) | Comparison of the fluctuation range of blood pressure during surgery and in the recovery room (up to 2hours post-surgery) |
| Perioperative Hemodynamic Stability: Heart rate Fluctuation | During surgery and in the recovery room (up to 2hours post-surgery)(Day 0) | Comparison of the fluctuation range of Heart rate during surgery and in the recovery room (up to 2hours post-surgery) |
| Postoperative Cardiovascular and Respiratory Complications Rate | Within 30 days after surgery | Incidence of major cardiovascular and respiratory complications, including MI, CVA, MINS, and pulmonary complications. |
| length of hospital stay | Within 30 days after surgery | Total number of days from the date of surgery to the date of discharge. |
| Change in Patient-Reported Anxiety (HADS-A) | Baseline (Screening), Just before surgery (Day 0), and 6 months after surgery | Evaluation of the change in anxiety levels using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale. The score ranges from 0 to 21, with higher scores indicating higher anxiety. |
Countries
South Korea
Contacts
CONTACTJinah Lee, MD
CONTACTChang Ik Yoon, MD, Ph.D.
PRINCIPAL_INVESTIGATORChang Ik Yoon, MD, Ph.D.
Seoul St. Mary's Hospital, The Catholic University of Korea
Outcome results
None listed