Impact of Propranolol Strategies on Myocardial Injury After Breast Cancer Surgery

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:

• Propranolol Group: Patients receive propranolol for at least 14 days before surgery.
• 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.

Inclusion criteria

• Female patients aged 20 to 70 years.
• Patients diagnosed with hypertension or angina who require medication.
• Patients diagnosed with unilateral, resectable primary breast cancer (ICD-10: C50), Stage I-III.
• ECOG performance status of 0-1.
• Patients scheduled to receive standard postoperative treatment (including adjuvant radiotherapy
• Patients who voluntarily decide to participate and sign the written informed consent form

Exclusion criteria

• Patients with distant metastases.
• Patients with active infectious diseases, autoimmune diseases (including specific rheumatic diseases), coagulation disorders, or cardiovascular diseases other than hypertension or angina pectoris.
• 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)
• Patients with moderate to severe asthma or chronic obstructive pulmonary disease (COPD).
• Patients who are pregnant or breastfeeding at the time of enrollment.
• Patients with a history of malignancy within the past 5 years.
• Patients for whom data collection is considered difficult at the discretion of the investigator.
• Patients who are unable to understand or complete study questionnaires.
• Patients who have received β-blockers within 30 days prior to screening.
• Patients with systolic blood pressure < 100 mmHg or heart rate < 55 beats per minute.