Effect of Physical Exercise on Tumor Proliferation of Luminal B Breast Cancer Patients

Breast Cancer Clinical Trial

— EFIK  

Official title:

Effect of Physical Exercise on Ki-67 Levels in Women With Operable Breast Cancer Hormonal Receptor Positive, HER2 Negative

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03860740
• Other study ID #: GEICAM/2014-09
• Status: Completed
• Start date: June 2016
• Est. completion date: June 8, 2021

Study information

• Verified date: January 2023
• Source: Spanish Breast Cancer Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Observational study to evaluate the effect of physical exercise prior to surgery and adjuvant systemic treatment in women with newly diagnosed operable hormone receptor(HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers

Description:

Effect of exercise on tumor aggressiveness and the impact on patients' quality of life.

Exercise is a safe and effective treatment for women diagnosed with breast cancer (BC), that has an integral benefit during and after treatments, however, the effect at the tumour microenvironment it is unknown; previous studies have evaluated the association between exercise and BC, finding a positive influence on it, which suggest that exercise could reduce the aggressiveness of the tumour. This study will explore the exercise impact in tumor microenvironment, as part of the therapy given to the patients prior to surgery and treatment. In addition, different serum biomarkers involved and the tailoring of exercise for these women will be evaluated. The effect of exercise on treatments secondary effects, biomarkers and quality of life will be evaluated after 6 months of BC surgery. This project will open a window of opportunity to explore new translational research as well as new treatment vias to the patients of this breast cancer subgroup.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 8, 2021
• Est. primary completion date: June 8, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed, previously untreated clinical stage I-IIIA without previous treatment.

• ER positive breast cancer according to local results. (RH+ is defined as = 1% assessed by Immunohistochemistry (IHC) to Estrogen Receptor (ER) and/or Progesterone Receptor (P)E).

• HER2 negative in the primary tumour according to local results. (HER2 confirmation should be done following the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2013 guidelines)

• Scheduled to undergo surgical resection.

• Ki67 levels must be over 13%, according to local results.

• At least 14 days from enrolment to planned surgical resection.

• Karnofsky performance status of at least 70% at study entry or 0-1 level in Eastern Cooperative Oncology Group (ECOG) Scale.

• Signed consent prior to initiation of study-related procedures.

Exclusion Criteria:

• Schedule to receive any form of induction/neoadjuvant therapy

• Significant cardiac disease (ventricular ejection fraction of <50%, unstable angina, placement of cardiac stents and myocardial infarction within precious 6 months)

• Any pulmonary dysfunction which may affect to the exercise program perform.

• Any mental disease or condition that compromise the physical, psychological and emotional patients' wellness or affect to the process.

• Contraindications to a cardiopulmonary exercise test as recommended by the American Thoracic Society.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Luminal B

Intervention

Other:
• Exercise
Exercise intervention adapted to maximum rate of oxygen consumption measured during incremental exercise (VO2level) of each patient, working between 60% to 100% VO2level. The activity will be walk-run in a treadmill. 10 sessions minimum
• Stretching
Stretching and relaxing exercise during 30 minutes. Same number of sessions as intervention group

Locations

Country	Name	City	State
Spain	Hospital General Universitario Gregorio Marañón	Madrid

Sponsors (3)

Lead Sponsor	Collaborator
Spanish Breast Cancer Research Group	Faculty of Physical Activity and Sport Sciences (INEF), Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

Country where clinical trial is conducted

Spain, 

References & Publications (25)

Battaglini C, Bottaro M, Dennehy C, Rae L, Shields E, Kirk D, Hackney AC. The effects of an individualized exercise intervention on body composition in breast cancer patients undergoing treatment. Sao Paulo Med J. 2007 Jan 4;125(1):22-8. doi: 10.1590/s1516-31802007000100005. Erratum In: Sao Paulo Med J. 2007 Sep 6;125(5):303. Hackney, Anthony [corrected to Hackney, Anthony Carl]. — View Citation

Bertolini F. Adipose tissue and breast cancer progression: a link between metabolism and cancer. Breast. 2013 Aug;22 Suppl 2:S48-9. doi: 10.1016/j.breast.2013.07.009. — View Citation

Betof AS, Dewhirst MW, Jones LW. Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain Behav Immun. 2013 Mar;30 Suppl(0):S75-87. doi: 10.1016/j.bbi.2012.05.001. Epub 2012 May 17. — View Citation

Burgomaster KA, Hughes SC, Heigenhauser GJ, Bradwell SN, Gibala MJ. Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans. J Appl Physiol (1985). 2005 Jun;98(6):1985-90. doi: 10.1152/japplphysiol.01095.2004. Epub 2005 Feb 10. — View Citation

Chirlaque MD, Salmeron D, Ardanaz E, Galceran J, Martinez R, Marcos-Gragera R, Sanchez MJ, Mateos A, Torrella A, Capocaccia R, Navarro C. Cancer survival in Spain: estimate for nine major cancers. Ann Oncol. 2010 May;21 Suppl 3:iii21-29. doi: 10.1093/annonc/mdq082. — View Citation

Demark-Wahnefried W, Case LD, Blackwell K, Marcom PK, Kraus W, Aziz N, Snyder DC, Giguere JK, Shaw E. Results of a diet/exercise feasibility trial to prevent adverse body composition change in breast cancer patients on adjuvant chemotherapy. Clin Breast Cancer. 2008 Feb;8(1):70-9. doi: 10.3816/CBC.2008.n.005. — View Citation

Demark-Wahnefried W, Kenyon AJ, Eberle P, Skye A, Kraus WE. Preventing sarcopenic obesity among breast cancer patients who receive adjuvant chemotherapy: results of a feasibility study. Clin Exerc Physiol. 2002 Feb;4(1):44-49. — View Citation

Herrero F, San Juan AF, Fleck SJ, Balmer J, Perez M, Canete S, Earnest CP, Foster C, Lucia A. Combined aerobic and resistance training in breast cancer survivors: A randomized, controlled pilot trial. Int J Sports Med. 2006 Jul;27(7):573-80. doi: 10.1055/s-2005-865848. — View Citation

Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity and survival after breast cancer diagnosis. JAMA. 2005 May 25;293(20):2479-86. doi: 10.1001/jama.293.20.2479. — View Citation

Ibrahim EM, Al-Homaidh A. Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies. Med Oncol. 2011 Sep;28(3):753-65. doi: 10.1007/s12032-010-9536-x. Epub 2010 Apr 22. — View Citation

Irwin ML, McTiernan A, Baumgartner RN, Baumgartner KB, Bernstein L, Gilliland FD, Ballard-Barbash R. Changes in body fat and weight after a breast cancer diagnosis: influence of demographic, prognostic, and lifestyle factors. J Clin Oncol. 2005 Feb 1;23(4):774-82. doi: 10.1200/JCO.2005.04.036. — View Citation

Irwin ML, Smith AW, McTiernan A, Ballard-Barbash R, Cronin K, Gilliland FD, Baumgartner RN, Baumgartner KB, Bernstein L. Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study. J Clin Oncol. 2008 Aug 20;26(24):3958-64. doi: 10.1200/JCO.2007.15.9822. — View Citation

Irwin ML. Physical activity interventions for cancer survivors. Br J Sports Med. 2009 Jan;43(1):32-8. doi: 10.1136/bjsm.2008.053843. Epub 2008 Oct 23. — View Citation

Jones LW, Demark-Wahnefried W. Diet, exercise, and complementary therapies after primary treatment for cancer. Lancet Oncol. 2006 Dec;7(12):1017-26. doi: 10.1016/S1470-2045(06)70976-7. — View Citation

Jones LW, Fels DR, West M, Allen JD, Broadwater G, Barry WT, Wilke LG, Masko E, Douglas PS, Dash RC, Povsic TJ, Peppercorn J, Marcom PK, Blackwell KL, Kimmick G, Turkington TG, Dewhirst MW. Modulation of circulating angiogenic factors and tumor biology by aerobic training in breast cancer patients receiving neoadjuvant chemotherapy. Cancer Prev Res (Phila). 2013 Sep;6(9):925-37. doi: 10.1158/1940-6207.CAPR-12-0416. Epub 2013 Jul 10. — View Citation

Jones LW, Liang Y, Pituskin EN, Battaglini CL, Scott JM, Hornsby WE, Haykowsky M. Effect of exercise training on peak oxygen consumption in patients with cancer: a meta-analysis. Oncologist. 2011;16(1):112-20. doi: 10.1634/theoncologist.2010-0197. Epub 2011 Jan 6. Erratum In: Oncologist. 2011;16(2):260. — View Citation

Jones LW, Peddle CJ, Eves ND, Haykowsky MJ, Courneya KS, Mackey JR, Joy AA, Kumar V, Winton TW, Reiman T. Effects of presurgical exercise training on cardiorespiratory fitness among patients undergoing thoracic surgery for malignant lung lesions. Cancer. 2007 Aug 1;110(3):590-8. doi: 10.1002/cncr.22830. — View 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. Erratum In: J Appl Physiol. 2010 Apr;108(4):1021. — View Citation

Mishra SI, Scherer RW, Geigle PM, Berlanstein DR, Topaloglu O, Gotay CC, Snyder C. Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database Syst Rev. 2012 Aug 15;2012(8):CD007566. doi: 10.1002/14651858.CD007566.pub2. — View Citation

Pedersen BK. Muscle as a secretory organ. Compr Physiol. 2013 Jul;3(3):1337-62. doi: 10.1002/cphy.c120033. — View 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. — View Citation

Schmitz KH, Ahmed RL, Yee D. Effects of a 9-month strength training intervention on insulin, insulin-like growth factor (IGF)-I, IGF-binding protein (IGFBP)-1, and IGFBP-3 in 30-50-year-old women. Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1597-604. — View Citation

Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM, Irwin ML, Wolin KY, Segal RJ, Lucia A, Schneider CM, von Gruenigen VE, Schwartz AL; American College of Sports Medicine. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010 Jul;42(7):1409-26. doi: 10.1249/MSS.0b013e3181e0c112. Erratum In: Med Sci Sports Exerc. 2011 Jan;43(1):195. — View Citation

Speck RM, Courneya KS, Masse LC, Duval S, Schmitz KH. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv. 2010 Jun;4(2):87-100. doi: 10.1007/s11764-009-0110-5. Epub 2010 Jan 6. Erratum In: J Cancer Surviv. 2011 Mar;5(1):112. — View Citation

Zeng H, Irwin ML, Lu L, Risch H, Mayne S, Mu L, Deng Q, Scarampi L, Mitidieri M, Katsaros D, Yu H. Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1. Breast Cancer Res Treat. 2012 May;133(1):127-35. doi: 10.1007/s10549-011-1716-7. Epub 2011 Aug 12. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor proliferation (Ki67)	Tumor proliferation (Ki67) will be assessed immunohistochemically at basal biopsies versus post-surgery tumor samples.	Post-surgery, an average of 6 months
Primary	Proliferation Score	A 50-gene quantitative polymerase chain reaction (qPCR) assay (PAM50) will be used to identify the intrinsic biological subtypes using RNA isolated from formalin-fixed, paraffin-embedded (FFPE) tissue from baseline biopsies samples and post-surgery tumor samples.	Post-surgery, an average of 6 months
Secondary	Change from baseline molecular subtypes	A 50-gene qPCR assay (PAM50) will be used to identify the intrinsic biological subtypes using RNA isolated from formalin-fixed, paraffin-embedded (FFPE) tissue from baseline biopsies samples and post-surgery tumor samples.	Post-surgery, an average of 6 months
Secondary	Changes in tumor microenvironment: levels of Vascular endothelial growth factor (VEGF)	VEGF will be evaluated on tissue from baseline biopsies samples and post-surgery tumor samples by Immunohistochemistry (IHC)	Post-surgery, an average of 6 months
Secondary	Changes in tumor microenvironment: levels of factor Hypoxia-inducible factor 1 (HIF-1)	HIF-1 will be evaluated on tissue from baseline biopsies samples and post-surgery tumor samples by Immunohistochemistry (IHC)	Post-surgery, an average of 6 months
Secondary	Change in tumor microenvironment: levels of cleaved caspase 3	Levels of cleaved caspase 3 will be evaluated on tissue from baseline biopsies samples and post-surgery tumor samples by Immunohistochemistry (IHC)	Post-surgery, an average of 6 months
Secondary	Oxygen uptake during peak exercise (VO2peak)	VO2peak will be obtained of the Cardiopulmonary exercise testing (CPET) performed at baseline and after the exercise program until surgery.	Post-surgery, an average of 6 months
Secondary	Change in body composition	Change in body composition will be assessed by bioimpedance parameters. Bioelectrical impedance analysis (BIA) is a commonly used method for estimating body composition, and in particular body fat, and will be performed at baseline and after the exercise program until surgery.	Post-surgery, an average of 6 months
Secondary	Change in fatigue levels	Change in fatigue levels will be assessed by questionnaire Functional Assessment of Cancer Therapy: Fatigue (FACT-F). The physical well-being domain has 7 items with scores from 0 to 28 points; social/family well-being, 7 items with score from 0 to 28 points; emotional well-being, 6 items with score from 0 to 24 points; functional well-being, 7 items with score from 0 to 28 points; and fatigue subscale, 13 items with score from 0 to 52. Each item has ?ve likert-type options graduated from 0 to 4: "Not at all", "A little bit"; Somewhat"; "Quite a bit"; "Very much'. The ?nal score of FACT-F is obtained by adding the scores of the ?ve domains, and may vary from 0 to 160 points. The higher the number of points, the better the quality of life and the less the fatigue of the patients is. To obtain the score, the negative questions are reverted; then the answers of the domains are added up, and a proportional average is carried out in case of non answered items.	Post-surgery, an average of 6 months
Secondary	Change in quality of life levels	Change in quality of life levels will be assessed by questionnaire Functional Assessment of Cancer Therapy: Breast Cancer (FACT-B). The FACT-B is a breast cancer-specific HRQoL instrument of the FACIT system. The 37-item are divided into five subscales, namely physical (PWB), social/family (SWB), emotional (EWB), functional well-beings (FWB), and the additional concerns for breast cancer (BCS). Each item is rated on a 5-point Likert scale. Negatively worded items were recoded such that a higher score indicates a better HRQoL. The FACT-B total score is the sum of scores of all five subscales.	Post-surgery, an average of 6 months
Secondary	Change in depression levels	Change in depression levels will be assessed by questionnaire Center for Epidemiologic Studies Depression Scale (CES-D). The CES-D is a 20-item measure assessing symptoms of depression with items phrased as self-statements (e.g., "I felt hopeful about the future"). Respondents rate how frequently each item applied to them over the course of the past week. Ratings were based on a 4-point Likert scale ranging from 0 (rarely or none of the time [less than 1 day]) to 3 (most or all of the time [5-7 days]).	Post-surgery, an average of 6 months

External Links

•   Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group