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

Completed
Conditions
Luminal B
Breast Cancer
Interventions
Other: Exercise
Other: Stretching
Registration Number
NCT03860740
Lead Sponsor
Spanish Breast Cancer Research Group
Brief 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

Detailed 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 & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
12
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
High intensity physical exerciseExerciseSupervised Exercise Group: Customized and supervised exercise high intensity training program during 2-3 weeks previous surgery.
ControlStretchingSupervised Stretching Group: a stretching and body balance classes will be developed to control the possible confounders and to control the exercise level of participants.
Primary Outcome Measures
NameTimeMethod
Proliferation ScorePost-surgery, an average of 6 months

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.

Tumor proliferation (Ki67)Post-surgery, an average of 6 months

Tumor proliferation (Ki67) will be assessed immunohistochemically at basal biopsies versus post-surgery tumor samples.

Secondary Outcome Measures
NameTimeMethod
Changes in tumor microenvironment: levels of factor Hypoxia-inducible factor 1 (HIF-1)Post-surgery, an average of 6 months

HIF-1 will be evaluated on tissue from baseline biopsies samples and post-surgery tumor samples by Immunohistochemistry (IHC)

Change in tumor microenvironment: levels of cleaved caspase 3Post-surgery, an average of 6 months

Levels of cleaved caspase 3 will be evaluated on tissue from baseline biopsies samples and post-surgery tumor samples by Immunohistochemistry (IHC)

Changes in tumor microenvironment: levels of Vascular endothelial growth factor (VEGF)Post-surgery, an average of 6 months

VEGF will be evaluated on tissue from baseline biopsies samples and post-surgery tumor samples by Immunohistochemistry (IHC)

Oxygen uptake during peak exercise (VO2peak)Post-surgery, an average of 6 months

VO2peak will be obtained of the Cardiopulmonary exercise testing (CPET) performed at baseline and after the exercise program until surgery.

Change from baseline molecular subtypesPost-surgery, an average of 6 months

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.

Change in body compositionPost-surgery, an average of 6 months

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.

Change in quality of life levelsPost-surgery, an average of 6 months

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.

Change in depression levelsPost-surgery, an average of 6 months

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 \[5-7 days\]).

Change in fatigue levelsPost-surgery, an average of 6 months

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 five likert-type options graduated from 0 to 4: "Not at all", "A little bit"; Somewhat"; "Quite a bit"; "Very much'. The final score of FACT-F is obtained by adding the scores of the five 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.

Trial Locations

Locations (1)

Hospital General Universitario Gregorio Marañón

🇪🇸

Madrid, Spain

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