Impact of Propranolol Strategies on Myocardial Injury After Breast Cancer Surgery (B-BIT)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Myocardial Injury After Noncardiac Surgery (MINS)
• Intervention / Treatment: Drug: propranolol; Other: Usual Care

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jinah Lee, MD; Phone Number: 82-10-8573-9324; Email: jinahsmile@naver.com
• Study Contact Backup: Name: Chang Ik Yoon, MD, Ph.D.; Phone Number: 82-10-8774-0103; Email: fayn@daum.net

Study Locations

• South Korea
  • Seoul
    • Seoul, Seoul, South Korea, 06591
      • Seoul St. Mary's Hospital, The Catholic University of Korea
      • Contact: Jinah Lee, MD; Phone Number: 82-10-8573-9324; Email: jinahsmile@naver.com
      • Contact: Chang Ik Yoon, MD, Ph.D.; Phone Number: 82-10-8774-0103; Email: fayn@daum.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propranolol Group; Participants with hypertension or angina undergoing breast cancer surgery will receive Propranolol (dosage based on clinical indication) for at least 14 days before surgery until the morning of the operation.	Drug: propranolol; Propranolol (dosage based on clinical indication) for at least 14 days before surgery until the morning of the operation.
Active Comparator: Non-Propranolol Group (Usual Care); Participants will receive standard clinical care for hypertension or angina without the use of Propranolol or other beta-blockers before surgery	Other: Usual Care; Standard medical management (e.g., CCB, ACEi, ARB, or diuretics) at the physician's discretion, excluding beta-blockers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Myocardial Injury after Noncardiac Surgery (MINS)	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: 0.02-0.065 ng/mL with an absolute change of more than 0.005ng/mL or; any elevation ≥0.065 ng/mL or any absolute change more than 0.014 ng/mL	From the day of surgery (Day 0) up to 30 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative Hemodynamic Stability: Systolic Blood Pressure Fluctuation	Comparison of the fluctuation range of blood pressure during surgery and in the recovery room (up to 2hours post-surgery)	During surgery and in the recovery room (up to 2hours post-surgery)(Day 0)
Perioperative Hemodynamic Stability: Heart rate Fluctuation	Comparison of the fluctuation range of Heart rate during surgery and in the recovery room (up to 2hours post-surgery)	During surgery and in the recovery room (up to 2hours post-surgery)(Day 0)
Postoperative Cardiovascular and Respiratory Complications Rate	Incidence of major cardiovascular and respiratory complications, including MI, CVA, MINS, and pulmonary complications.	Within 30 days after surgery
length of hospital stay	Total number of days from the date of surgery to the date of discharge.	Within 30 days after surgery
Change in Patient-Reported Anxiety (HADS-A)	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.	Baseline (Screening), Just before surgery (Day 0), and 6 months after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Microenvironment and Biological Markers: Ki-67 Proliferation Index	The percentage of Ki-67 positive tumor cells measured by immunohistochemistry in surgical tissues.	At the time of surgery (Day 0)
Tumor Microenvironment and Biological Markers: Histological Grade	Assessment of tumor differentiation using the Modified Bloom-Richardson grade. The scale ranges from 3 to 9, where higher scores indicate a more aggressive tumor/worse outcome.	At the time of surgery (Day 0)
Tumor Microenvironment and Biological Markers: Presence of Lymphovascular Invasion	Pathological assessment of the presence or absence of tumor cells within lymphatic or vascular channels in the surgical specimen.	At the time of surgery (Day 0)
Tumor Microenvironment and Biological Markers: Tumor-Infiltrating Lymphocytes (TILs)	Percentage of stromal area occupied by mononuclear inflammatory cells in the surgical specimen.	At the time of surgery (Day 0)
Changes in Inflammatory Markers and Serum Tumor Markers: C-Reactive Protein (CRP)	Comparison of changes in C-reactive protein (CRP)	Baseline (Screening), Day 0 (Surgery), and 6 months after surgery
Changes in Inflammatory Markers and Serum Tumor Markers: lactate dehydrogenase (LDH)	Comparison of changes in lactate dehydrogenase (LDH)	Baseline (Screening), Day 0 (Surgery), and 6 months after surgery
Changes in Inflammatory Markers and Serum Tumor Markers: Carcinoembryonic Antigen (CEA)	Comparison of changes in serum tumor marker CEA	Baseline (Screening), Day 0 (Surgery), and 6 months after surgery
Changes in Inflammatory Markers and Serum Tumor Markers: Cancer Antigen 15-3 (CA 15-3)	Comparison of changes in serum tumor markers CA 15-3	Baseline (Screening), Day 0 (Surgery), and 6 months after surgery
Long-term Recurrence and Survival Outcomes	Descriptive analysis of recurrence status, invasive disease-free survival (iDFS), and overall survival (OS)	Up to 5 years after surgery
Molecular and Immunological Analysis	Exploration of biological changes related to propranolol use through molecular analysis (e.g., RNA/DNA sequencing) using stored tissue and blood samples.	Up to 5 years (duration of sample storage and analysis)

Collaborators and Investigators

• Sponsor: Chang-Ik Yoon
• Collaborators: Seoul St. Mary's Hospital
• Investigators: Principal Investigator: Chang Ik Yoon, MD, Ph.D., Seoul St. Mary's Hospital, The Catholic University of Korea

Publications and helpful links

General Publications

• 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 L, Gerstein H, Paniagua P, Nagele P, Raina P, Yusuf S, Devereaux PJ, Devereaux PJ, Sessler DI, Walsh M, Guyatt G, McQueen MJ, Bhandari M, Cook D, Bosch J, Buckley N, Yusuf S, Chow CK, Hillis GS, Halliwell R, Li S, Lee VW, Mooney J, Polanczyk CA, Furtado MV, Berwanger O, Suzumura E, Santucci E, Leite K, Santo JA, Jardim CA, Cavalcanti AB, Guimaraes HP, Jacka MJ, Graham M, McAlister F, McMurtry S, Townsend D, Pannu N, Bagshaw S, Bessissow A, Bhandari M, Duceppe E, Eikelboom J, Ganame J, Hankinson J, Hill S, Jolly S, Lamy A, Ling E, Magloire P, Pare G, Reddy D, Szalay D, Tittley J, Weitz J, Whitlock R, Darvish-Kazim S, Debeer J, Kavsak P, Kearon C, Mizera R, O'Donnell M, McQueen M, Pinthus J, Ribas S, Simunovic M, Tandon V, Vanhelder T, Winemaker M, Gerstein H, McDonald S, O'Bryne P, Patel A, Paul J, Punthakee Z, Raymer K, Salehian O, Spencer F, Walter S, Worster A, Adili A, Clase C, Cook D, Crowther M, Douketis J, Gangji A, Jackson P, Lim W, Lovrics P, Mazzadi S, Orovan W, Rudkowski J, Soth M, Tiboni M, Acedillo R, Garg A, Hildebrand A, Lam N, Macneil D, Mrkobrada M, Roshanov PS, Srinathan SK, Ramsey C, John PS, Thorlacius L, Siddiqui FS, Grocott HP, McKay A, Lee TW, Amadeo R, Funk D, McDonald H, Zacharias J, Villar JC, Cortes OL, Chaparro MS, Vasquez S, Castaneda A, Ferreira S, Coriat P, Monneret D, Goarin JP, Esteve CI, Royer C, Daas G, Chan MT, Choi GY, Gin T, Lit LC, Xavier D, Sigamani A, Faruqui A, Dhanpal R, Almeida S, Cherian J, Furruqh S, Abraham V, Afzal L, George P, Mala S, Schunemann H, Muti P, Vizza E, Wang CY, Ong GS, Mansor M, Tan AS, Shariffuddin II, Vasanthan V, Hashim NH, Undok AW, Ki U, Lai HY, Ahmad WA, Razack AH, Malaga G, Valderrama-Victoria V, Loza-Herrera JD, De Los Angeles Lazo M, Rotta-Rotta A, Szczeklik W, Sokolowska B, Musial J, Gorka J, Iwaszczuk P, Kozka M, Chwala M, Raczek M, Mrowiecki T, Kaczmarek B, Biccard B, Cassimjee H, Gopalan D, Kisten T, Mugabi A, Naidoo P, Naidoo R, Rodseth R, Skinner D, Torborg A, Paniagua P, Urrutia G, Maestre ML, Santalo M, Gonzalez R, Font A, Martinez C, Pelaez X, De Antonio M, Villamor JM, Garcia JA, Ferre MJ, Popova E, Alonso-Coello P, Garutti I, Cruz P, Fernandez C, Palencia M, Diaz S, Del Castillo T, Varela A, de Miguel A, Munoz M, Pineiro P, Cusati G, Del Barrio M, Membrillo MJ, Orozco D, Reyes F, Sapsford RJ, Barth J, Scott J, Hall A, Howell S, Lobley M, Woods J, Howard S, Fletcher J, Dewhirst N, Williams C, Rushton A, Welters I, Leuwer M, Pearse R, Ackland G, Khan A, Niebrzegowska E, Benton S, Wragg A, Archbold A, Smith A, McAlees E, Ramballi C, Macdonald N, Januszewska M, Stephens R, Reyes A, Paredes LG, Sultan P, Cain D, Whittle J, Del Arroyo AG, Sessler DI, Kurz A, Sun Z, Finnegan PS, Egan C, Honar H, Shahinyan A, Panjasawatwong K, Fu AY, Wang S, Reineks E, Nagele P, Blood J, Kalin M, Gibson D, Wildes T; Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Writing Group, on behalf of The Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Investigators; Appendix 1. The Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Study Investigators Writing Group; Appendix 2. The Vascular events In noncardiac Surgery patIents cOhort evaluatioN Operations Committee; Vascular events In noncardiac Surgery patIents cOhort evaluatioN VISION Study Investigators. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology. 2014 Mar;120(3):564-78. doi: 10.1097/ALN.0000000000000113.
• 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, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga G, Nagele P, Le Manach Y, Leuwer M, Yusuf S. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012 Jun 6;307(21):2295-304. doi: 10.1001/jama.2012.5502.
• 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.
• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): May 26, 2026
• Primary Completion (Estimated): May 23, 2028
• Study Completion (Estimated): May 24, 2033

Study Registration Dates

• First Submitted: April 27, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Beta-blockers; Propranolol; Tumor Microenvironment; Breast Cancer Surgery; Pragmatic Clinical Trial
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Amines; Alcohols; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Propranolol
• Other Study ID Numbers: KC26MISV0115; KCT0011912 (Other Identifier: Clinical Research Information Service)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No