Impact of Propranolol Strategies on Myocardial Injury After Breast Cancer Surgery

Official title

A Pragmatic Clinical Trial to Evaluate the Impact of Clinical Propranolol Strategies on Myocardial Injury After Non-cardiac Surgery (MINS) in Patients Undergoing Breast Cancer Surgery With Hypertension or Angina

Overview

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

• Drug propranolol
  Propranolol (dosage based on clinical indication) for at least 14 days before surgery until the morning of the operation.
• Other Usual Care
  Standard medical management (e.g., CCB, ACEi, ARB, or diuretics) at the physician's discretion, excluding beta-blockers.

Primary outcome measures

• Incidence of Myocardial Injury after Noncardiac Surgery (MINS) [Time frame: From the day of surgery (Day 0) up to 30 days postoperatively]

Secondary outcome measures (5)

• Perioperative Hemodynamic Stability: Systolic Blood Pressure Fluctuation [Time frame: During surgery and in the recovery room (up to 2hours post-surgery)(Day 0)]
• Perioperative Hemodynamic Stability: Heart rate Fluctuation [Time frame: During surgery and in the recovery room (up to 2hours post-surgery)(Day 0)]
• Postoperative Cardiovascular and Respiratory Complications Rate [Time frame: Within 30 days after surgery]
• length of hospital stay [Time frame: Within 30 days after surgery]
• Change in Patient-Reported Anxiety (HADS-A) [Time frame: Baseline (Screening), Just before surgery (Day 0), and 6 months after surgery]

Eligibility criteria

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.

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

Prevention

Study locations

South Korea · 1 center

• Seoul St. Mary's Hospital, The Catholic University of Korea — Seoul

Publications

• O'Logbon J, Tarantola L, Williams NR, Mehta S, Ahmed A, Davies EA. Does propranolol have a role in cancer treatment? A systematic review of the epidemiological and clinical trial literature on beta-blockers. J Cancer Res Clin Oncol. 2025 Jul 12;151(7):212. doi: 10.1007/s00432-025-06262-2. PMID 40652143
• Hiller JG, Cole SW, Crone EM, Byrne DJ, Shackleford DM, Pang JB, Henderson MA, Nightingale SS, Ho KM, Myles PS, Fox S, Riedel B, Sloan EK. Preoperative beta-Blockade with Propranolol Reduces Biomarkers of Metastasis in Breast Cancer: A Phase II Randomized Trial. Clin Cancer Res. 2020 Apr 15;26(8):1803-1811. doi: 10.1158/1078-0432.CCR-19-2641. Epub 2019 Nov 21. PMID 31754048
• Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators; Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F, Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rods PMID 22706835
• Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, Guyatt G, Cruz P, Graham M, Wang CY, Berwanger O, Pearse RM, Biccard BM, Abraham V, Malaga G, Hillis GS, Rodseth RN, Cook D, Polanczyk CA, Szczeklik W, Sessler DI, Sheth T, Ackland GL, Leuwer M, Garg AX, Lemanach Y, Pettit S, Heels-Ansdell D, Luratibuse G, Walsh M, Sapsford R, Schunemann HJ, Kurz A, Thomas S, Mrkobrada M, Thabane PMID 24534856

Identifiers

NCT: NCT07583134 · KC26MISV0115 · KCT0011912

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗