Clinical trial NCT06360809: Prehabilitation Exercise Program in Breast Cancer: Effects on Quality of Life and Tumor Microenvironment (PEP_BC)
Official title: Prehabilitation Exercise Program in Breast Cancer: Effects on Quality of Life and Tumor Microenvironment (PEP_BC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: breast cancer
physical exercise
tumor microenvironment
oxidative hemodynamics
near-infrared spectroscopy
diffuse correlation optical spectroscopy
prehabilitation therapy
Lead sponsor: Institut Nacional d'Educacio Fisica de Catalunya
Sponsor class: OTHER
Collaborators: name: ICFO - The Institute of Photonics Sciences
name: Hospital Clinic of Barcelona
name: Institut d'Investigacions Biomèdiques August Pi i Sunyer
name: Universidad San Jorge
First posted: 2024-04-11
Enrollment: 76
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To improve the health and quality of life of breast cancer (BC) patients, researchers are focusing on prehabilitation strategies like physical exercise, preparing patients both mentally and physically for clinical and surgical procedures, potentially reducing complications. Physical exercise is also recognized as pivotal in optimizing chemotherapy. It can improve blood flow and oxygen supply in the microenvironment of the tumor (MT), potentially enhancing chemotherapy effectiveness. Although previous research has shown the benefits of preoperative exercise combined with chemotherapy in various cancer types, including BC, further investigation is needed into the exact effects of prehabilitation exercise (PE) on MT physiology.

This study aims to provide valuable insights into the potential benefits of PE for BC patients and its impact on the tumor microenvironment. The hypothesis is that PE in BC patients will improve their quality of life, reduce fatigue, increase muscle mass, decrease fat mass, and enhance physical fitness. Additionally, beneficial acute hemodynamic changes, particularly increased blood flow following PE sessions, and hemodynamic adaptations involving higher levels of oxygenated hemoglobin, increased blood flow, greater oxygen saturation, and a higher metabolic rate of oxygen, are expected.

The study will include 76 participants aged 18-65 years, meeting specific criteria such as a diagnosis of hormone receptor-positive BC, no medical contraindications for exercise, no metastatic cancer, and no structured exercise in the last six months. These participants will be randomly assigned to a PE group or a control group. The study will consist of three phases: Phase 1 involves pre-intervention assessments, Phase 2 includes a 4-week PE intervention with three weekly sessions, and Phase 3 encompasses post-intervention and post-surgery assessments. The 4-week PE intervention in Phase 2 will include strength and aerobic training. Quality of life and fatigue assessments will use questionnaires, and measurements will be made for fat mass, lean mass, bone density, and cardiorespiratory fitness. Strength measurements will be taken, and shoulder mobility will be evaluated. Hemodynamics of the MT will be assessed using a hybrid device combining Near-Infrared Spectroscopy and Diffuse Correlation Spectroscopy with ultrasound.


Eligibility criteria: Inclusion Criteria:

* Be aged between 18 and 65 years.
* Have a diagnosis of hormone receptor-positive breast cancer (ER and PR).
* Have no medical contraindications that prevent them from participating in physical exercise.
* Have four weeks period between diagnosis and surgery

Exclusion Criteria:

* Being diagnosed of another primary and/or secondary tumor or being in metastatic stage.
* Presence of uncontrolled serious medical illness
* Presence of any medical, psychological or social problem that could seriously interfere with the patient's participation in the study
* Those who have engaged in structured physical exercise in the last 6 months.

Primary outcomes:
measure: Quality of life score
timeFrame: 0, 28,and 35 days
measure: Cancer quality of life score
timeFrame: 0, 28,and 35 days
measure: Cancer-related fatigue
timeFrame: 0, 28,and 35 days
measure: Body composition
timeFrame: 0, 28,and 35 days
measure: Bone density
timeFrame: 0, 28,and 35 days
measure: Cardiorespiratory fitness
timeFrame: 0, 28,and 35 days
measure: Maximum isometric manual grip strength
timeFrame: 0, 28,and 35 days
measure: Upper body maximum strength
timeFrame: 0, 28,and 35 days
measure: Lower body maximum strength
timeFrame: 0, 28,and 35 days
measure: Shoulder range of motion
timeFrame: 0, 28,and 35 days
measure: Relative oxyhemoglobin concentration ([02Hb]) in the microenvironment of the tumor
timeFrame: 1 and 27 days
measure: Relative deoxyhemoglobin concentration ([HHb]) in the microenvironment of the tumor
timeFrame: 1 and 27 days
measure: Oxygen saturation (StO2) in the microenvironment of the tumor
timeFrame: 1 and 27 days
measure: Blood flow (BF) in the microenvironment of the tumor
timeFrame: 1 and 27 days
Secondary outcomes:
measure: Height
timeFrame: 0, 28,and 35 days
measure: Body mass
timeFrame: 0, 28,and 35 days
measure: Body mass index
timeFrame: 0, 28,and 35 days
measure: Wait circumference
timeFrame: 0, 28,and 35 days
measure: Anthropometric measurements
timeFrame: 0, 28,and 35 days
measure: Bioimpedance measurements
timeFrame: 0, 28,and 35 days
measure: Maximal heart rate
timeFrame: 0, 28,and 35 days
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic
Study officials:
affiliation: Institut Nacional d'Educació Física de Catalunya
name: Albert Busquets, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad San Jorge
name: Lucia Sagarra-Romero, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chong F, Wang Y, Song M, Sun Q, Xie W, Song C. Sedentary behavior and risk of breast cancer: a dose-response meta-analysis from prospective studies. Breast Cancer. 2021 Jan;28(1):48-59. doi: 10.1007/s12282-020-01126-8. Epub 2020 Jun 30.
citation: Lee K, Kruper L, Dieli-Conwright CM, Mortimer JE. The Impact of Obesity on Breast Cancer Diagnosis and Treatment. Curr Oncol Rep. 2019 Mar 27;21(5):41. doi: 10.1007/s11912-019-0787-1.
citation: Gillis C, Loiselle SE, Fiore JF Jr, Awasthi R, Wykes L, Liberman AS, Stein B, Charlebois P, Carli F. Prehabilitation with Whey Protein Supplementation on Perioperative Functional Exercise Capacity in Patients Undergoing Colorectal Resection for Cancer: A Pilot Double-Blinded Randomized Placebo-Controlled Trial. J Acad Nutr Diet. 2016 May;116(5):802-12. doi: 10.1016/j.jand.2015.06.007. Epub 2015 Jul 21.
citation: Santa Mina D, Hilton WJ, Matthew AG, Awasthi R, Bousquet-Dion G, Alibhai SMH, Au D, Fleshner NE, Finelli A, Clarke H, Aprikian A, Tanguay S, Carli F. Prehabilitation for radical prostatectomy: A multicentre randomized controlled trial. Surg Oncol. 2018 Jun;27(2):289-298. doi: 10.1016/j.suronc.2018.05.010. Epub 2018 May 7.
citation: Sebio Garcia R, Yanez Brage MI, Gimenez Moolhuyzen E, Granger CL, Denehy L. Functional and postoperative outcomes after preoperative exercise training in patients with lung cancer: a systematic review and meta-analysis. Interact Cardiovasc Thorac Surg. 2016 Sep;23(3):486-97. doi: 10.1093/icvts/ivw152. Epub 2016 May 25.
citation: Bozzetti F. Forcing the vicious circle: sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy. Ann Oncol. 2017 Sep 1;28(9):2107-2118. doi: 10.1093/annonc/mdx271.
citation: Lipsett A, Barrett S, Haruna F, Mustian K, O'Donovan A. The impact of exercise during adjuvant radiotherapy for breast cancer on fatigue and quality of life: A systematic review and meta-analysis. Breast. 2017 Apr;32:144-155. doi: 10.1016/j.breast.2017.02.002. Epub 2017 Feb 9.
citation: Travier N, Velthuis MJ, Steins Bisschop CN, van den Buijs B, Monninkhof EM, Backx F, Los M, Erdkamp F, Bloemendal HJ, Rodenhuis C, de Roos MA, Verhaar M, ten Bokkel Huinink D, van der Wall E, Peeters PH, May AM. Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial. BMC Med. 2015 Jun 8;13:121. doi: 10.1186/s12916-015-0362-z.
citation: Florez Bedoya CA, Cardoso ACF, Parker N, Ngo-Huang A, Petzel MQ, Kim MP, Fogelman D, Romero SG, Wang H, Park M, Katz MHG, Schadler KL. Exercise during preoperative therapy increases tumor vascularity in pancreatic tumor patients. Sci Rep. 2019 Sep 27;9(1):13966. doi: 10.1038/s41598-019-49582-3.
citation: Ashcraft KA, Warner AB, Jones LW, Dewhirst MW. Exercise as Adjunct Therapy in Cancer. Semin Radiat Oncol. 2019 Jan;29(1):16-24. doi: 10.1016/j.semradonc.2018.10.001.
citation: Schumacher O, Galvao DA, Taaffe DR, Chee R, Spry N, Newton RU. Exercise modulation of tumour perfusion and hypoxia to improve radiotherapy response in prostate cancer. Prostate Cancer Prostatic Dis. 2021 Mar;24(1):1-14. doi: 10.1038/s41391-020-0245-z. Epub 2020 Jul 6.
citation: Betof AS, Lascola CD, Weitzel D, Landon C, Scarbrough PM, Devi GR, Palmer G, Jones LW, Dewhirst MW. Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise. J Natl Cancer Inst. 2015 Mar 16;107(5):djv040. doi: 10.1093/jnci/djv040. Print 2015 May.
citation: Jones LW, Viglianti BL, Tashjian JA, Kothadia SM, Keir ST, Freedland SJ, Potter MQ, Moon EJ, Schroeder T, Herndon JE 2nd, Dewhirst MW. Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer. J Appl Physiol (1985). 2010 Feb;108(2):343-8. doi: 10.1152/japplphysiol.00424.2009. Epub 2009 Dec 3.
citation: Durduran T, Choe R, Yu G, Zhou C, Tchou JC, Czerniecki BJ, Yodh AG. Diffuse optical measurement of blood flow in breast tumors. Opt Lett. 2005 Nov 1;30(21):2915-7. doi: 10.1364/ol.30.002915.
citation: Nioka S, Chance B. NIR spectroscopic detection of breast cancer. Technol Cancer Res Treat. 2005 Oct;4(5):497-512. doi: 10.1177/153303460500400504.
citation: Teng F, Cormier T, Sauer-Budge A, Chaudhury R, Pera V, Istfan R, Chargin D, Brookfield S, Ko NY, Roblyer DM. Wearable near-infrared optical probe for continuous monitoring during breast cancer neoadjuvant chemotherapy infusions. J Biomed Opt. 2017 Jan 1;22(1):14001. doi: 10.1117/1.JBO.22.1.014001.
citation: Choe R, Durduran T. Diffuse Optical Monitoring of the Neoadjuvant Breast Cancer Therapy. IEEE J Sel Top Quantum Electron. 2012 Jul;18(4):1367-1386. doi: 10.1109/JSTQE.2011.2177963. Epub 2011 Dec 2.
citation: Choe R, Putt ME, Carlile PM, Durduran T, Giammarco JM, Busch DR, Jung KW, Czerniecki BJ, Tchou J, Feldman MD, Mies C, Rosen MA, Schnall MD, DeMichele A, Yodh AG. Optically measured microvascular blood flow contrast of malignant breast tumors. PLoS One. 2014 Jun 26;9(6):e99683. doi: 10.1371/journal.pone.0099683. eCollection 2014.
citation: Ramirez G, Proctor AR, Jung KW, Wu TT, Han S, Adams RR, Ren J, Byun DK, Madden KS, Brown EB, Foster TH, Farzam P, Durduran T, Choe R. Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy. Biomed Opt Express. 2016 Aug 24;7(9):3610-3630. doi: 10.1364/BOE.7.003610. eCollection 2016 Sep 1.
citation: Rao R, Cruz V, Peng Y, Harker-Murray A, Haley BB, Zhao H, Xie XJ, Euhus D. Bootcamp during neoadjuvant chemotherapy for breast cancer: a randomized pilot trial. Breast Cancer (Auckl). 2012;6:39-46. doi: 10.4137/BCBCR.S9221. Epub 2012 Feb 1.
citation: Busch DR, Choe R, Durduran T, Friedman DH, Baker WB, Maidment AD, Rosen MA, Schnall MD, Yodh AG. Blood flow reduction in breast tissue due to mammographic compression. Acad Radiol. 2014 Feb;21(2):151-61. doi: 10.1016/j.acra.2013.10.009.
citation: Sagarra-Romero L, Butragueno J, Gomez-Bruton A, Lozano-Berges G, Vicente-Rodriguez G, Morales JS. Effects of an online home-based exercise intervention on breast cancer survivors during COVID-19 lockdown: a feasibility study. Support Care Cancer. 2022 Jul;30(7):6287-6297. doi: 10.1007/s00520-022-07069-4. Epub 2022 Apr 26.
citation: Soriano-Maldonado A, Carrera-Ruiz A, Diez-Fernandez DM, Esteban-Simon A, Maldonado-Quesada M, Moreno-Poza N, Garcia-Martinez MDM, Alcaraz-Garcia C, Vazquez-Sousa R, Moreno-Martos H, Toro-de-Federico A, Hachem-Salas N, Artes-Rodriguez E, Rodriguez-Perez MA, Casimiro-Andujar AJ. Effects of a 12-week resistance and aerobic exercise program on muscular strength and quality of life in breast cancer survivors: Study protocol for the EFICAN randomized controlled trial. Medicine (Baltimore). 2019 Nov;98(44):e17625. doi: 10.1097/MD.0000000000017625.
citation: Nahvijou A, Safari H, Yousefi M, Rajabi M, Arab-Zozani M, Ameri H. Mapping the cancer-specific FACT-B onto the generic SF-6Dv2. Breast Cancer. 2021 Jan;28(1):130-136. doi: 10.1007/s12282-020-01141-9. Epub 2020 Jul 25.
citation: Klassen O, Schmidt ME, Scharhag-Rosenberger F, Sorkin M, Ulrich CM, Schneeweiss A, Potthoff K, Steindorf K, Wiskemann J. Cardiorespiratory fitness in breast cancer patients undergoing adjuvant therapy. Acta Oncol. 2014 Oct;53(10):1356-65. doi: 10.3109/0284186X.2014.899435. Epub 2014 May 16.
citation: Morishita S, Wakasugi T, Tanaka T, Harada T, Kaida K, Ikegame K, Ogawa H, Domen K. Changes in Borg scale for resistance training and test of exercise tolerance in patients undergoing allogeneic hematopoietic stem cell transplantation. Support Care Cancer. 2018 Sep;26(9):3217-3223. doi: 10.1007/s00520-018-4168-3. Epub 2018 Apr 6.
citation: Harrington S, Padua D, Battaglini C, Michener LA. Upper extremity strength and range of motion and their relationship to function in breast cancer survivors. Physiother Theory Pract. 2013 Oct;29(7):513-20. doi: 10.3109/09593985.2012.757683. Epub 2013 Jan 23.
citation: Cortese L, Lo Presti G, Zanoletti M, Aranda G, Buttafava M, Contini D, Dalla Mora A, Dehghani H, Di Sieno L, de Fraguier S, Hanzu FA, Mora Porta M, Nguyen-Dinh A, Renna M, Rosinski B, Squarcia M, Tosi A, Weigel UM, Wojtkiewicz S, Durduran T. The LUCA device: a multi-modal platform combining diffuse optics and ultrasound imaging for thyroid cancer screening. Biomed Opt Express. 2021 May 14;12(6):3392-3409. doi: 10.1364/BOE.416561. eCollection 2021 Jun 1.
citation: Cochran JM, Leproux A, Busch DR, O'Sullivan TD, Yang W, Mehta RS, Police AM, Tromberg BJ, Yodh AG. Breast cancer differential diagnosis using diffuse optical spectroscopic imaging and regression with z-score normalized data. J Biomed Opt. 2021 Feb;26(2):026004. doi: 10.1117/1.JBO.26.2.026004.
citation: Zhou C, Choe R, Shah N, Durduran T, Yu G, Durkin A, Hsiang D, Mehta R, Butler J, Cerussi A, Tromberg BJ, Yodh AG. Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy. J Biomed Opt. 2007 Sep-Oct;12(5):051903. doi: 10.1117/1.2798595.