Breast Cancer
Conditions
Keywords
breast cancer, physical activity, neoadjuvant chemotherapy, cardiooncology
Brief summary
The main goal of this study is to assess the impact of supervised intense physical activity (IPA) on outcomes of neoadjuvant chemotherapy in young women with breast cancer (YWBC). In this project standard neoadjuvant chemotherapy will be used concordant with summary of product characteristics (SPC). However during treatment (including days of chemotherapy application) an additional modifier of therapy will be carried out in the form of intense physical activity. This strategy is not recognized in SPC. This project aims to improve the results of breast cancer treatment in young women. According to available data, nowadays this subset of breast cancer patients has worse therapy results in comparison to older women. This is partially because of the different tumor characteristics; young women are more likely to present with human epithelial growth factor receptor 2 (HER2) receptor overexpression or with triple negative breast cancer. In the treatment of YWBC, preoperative chemotherapy is most often the first step. This enables the opportunity to assess the effectiveness of additional interventions in a mode it was never tested before. It is believed that physical activity improves the results of breast cancer treatment, however there are only few reports describing its benefit and role in terms of preoperative chemotherapy. In the current project, the investigators planned to introduce supervised increased physical activity concurrently with neoadjuvant treatment in YWBC at early stage of disease. The main goal of the study is to assess the effect of physical activity on preoperative chemotherapy outcomes. The change of tumor size after neoadjuvant chemotherapy, as well as the impact on Quality of Life (QoL) and Patients' Reported Outcome (PRO) in described above treatment modality. Secondary endpoints are the following: the pathologic Complete Response (pCR), disease free survival after 3 years (3-yr DFS), overall survival (OS), cardiotoxicity of treatment, the effect of physical activity on tumor microenvironment and Ki67 as well as the impact of increased physical activity on further patients' lifestyle changes.
Detailed description
The main goal of this study is to assess the impact of supervised intense physical activity (IPA) on outcomes of neoadjuvant chemotherapy in young women with breast cancer (YWBC). In this project standard neoadjuvant chemotherapy will be used concordant with summary of product characteristics (SPC). However during treatment (including days of chemotherapy application) an additional modifier of therapy will be carried out in the form of intense physical activity. This strategy is not recognized in SPC. This project aims to improve the results of breast cancer treatment in young women. According to available data, nowadays this subset of breast cancer patients has worse therapy results in comparison to older women. This is partially because of the different tumor characteristics; young women are more likely to present with human epithelial growth factor receptor 2 (HER2) receptor overexpression or with triple negative breast cancer. In the treatment of YWBC preoperative chemotherapy is most often the first step. This enables the opportunity to assess the effectiveness of additional interventions in a mode it was never tested before. It is believed that physical activity improves the results of breast cancer treatment, however there are only few reports describing its benefit and role in terms of preoperative chemotherapy. In the current project the investigators planned to introduce supervised increased physical activity concurrently with neoadjuvant treatment in YWBC at early stage of disease. The main goal of the study is to assess the effect of physical activity on preoperative chemotherapy outcomes. The change of tumor size after neoadjuvant chemotherapy, as well as the impact on Quality of Life (QoL) and Patients' Reported Outcome (PRO) in described above treatment modality. Secondary endpoints are the following: the pathologic Complete Response (pCR), disease free survival after 3 years (3-yr DFS), overall survival (OS), cardiotoxicity of treatment, the effect of physical activity on tumor microenvironment and Ki67 as well as the impact of increased physical activity on further patients' lifestyle changes. Patients aged 18 to 40 in good physical condition Eastern Cooperative Oncology Group (ECOG) 0-1 who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney, and bone marrow function as well as heart ejection fraction ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC). After receiving patients' agreement and signing informed consent form, the patient will undergo testing by a multidisciplinary panel of physicians. A cardiological assessment will be completed along with spiroergometry, bone density and anthropometric measurements. The patient will be asked to complete surveys assessing their QoL together with reporting their previous activity level and everyday functioning. Patients will be randomized into two groups - the comparator group undergoing chemotherapy and the intervention group in which additional intervention IPA will be ordered, in means of supervised high intensity interval training twice a week. Modalities of exercise will include: treadmill, elliptical, stationary bicycle and indoor rower. During the course of chemotherapy, the intensity of physical activity will be increasing. Moreover, throughout the entire therapy time, a 45-minute aerobic training session (e.g.: walk, jogging, roller skates, swimming) will be introduced once a week. In the control group, patients will be asked to independently perform their physical activity at an intensity and volume specified in general guidelines: 150-300 min. of moderate-intensity aerobic activity or 75-150 min. of vigorous aerobic activity. Each participant will be monitored at all times by the use of a standard biologic activity recording device. After the administration of anthracycline, the following procedures will be done: tumor/tumor bed core needle biopsy, mammography, breast ultrasound and cardiological assessment. Following the completion of chemotherapy all testing will be repeated with the exception of bone density measurement and core biopsy. These tests will be repeated one year after surgery. In addition, patients will be assessed for their immune status before and after chemotherapy, as well as one year of observation. When tissue material is available an assessment of the composition of inflammatory infiltrate will be performed using immunohistochemical stainings for immune cell markers. The investigators also planned to preserve material taken from the primary tumor and possible metastasis for molecular analysis (next generation sequencing (NGS), microarrays). The observation will be carried out for 10 years with own resources.
Interventions
OTHERHigh Intensity Interval Training (HIIT)
HIIT training twice a week throughout the chemotherapy: treadmill, elliptical, stationary bicycle and indoor rower. The intensity of physical activity will be increasing during consecutive mesocycles. Each training session will begin with a 10-min. wole-body warm-up session at 50-60% hear rate (HR) max. Mesocycle 1 - one month with 4 sets of 1 min. 45 sec. of exercise at a maximal intensity of 75% HR max. Mesocycle 2 with exercises at 80% to 90% HR max divided into 3 periods: 1/ one month, session of 5 sets 1 min. 30 sec. each; 2/ two months, sessions of 5 sets 1 min. 45 sec. each; 3/ two months, sessions of 5 sets 2 min. each. Moreover patients will be instructed to individually perform- a 45-min. aerobic training session (e.g.: walking, jogging, roller skating, swimming) once a week, in patient's own time.
DRUGneoadjuvant treatment (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab)
Patients aged 18 to 40 in good physical condition (Eastern Cooperative Oncology Group (ECOG) scale 0-1) who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney and bone marrow function as well as heart ejection fraction of ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).
Patients will be asked to perform 150-300 min. of moderate-intensity aerobic activity or 75-150 min. of vigorous aerobic activity. Each participant will be monitored by an activity watch worn at all times by the patient.
Sponsors
The Greater Poland Cancer Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be randomized into two groups. Patients which are set to receive neoadjuvant chemotherapy will be selected. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC). The group in which additional intervention IPA will be ordered, in means of supervised high intensity interval training twice a week. During the course of chemotherapy, the intensity of physical activity will be increasing. Moreover, throughout the entire therapy time, there will be introduced a 45-minute aerobic training session (e.g.: walk, jogging, roller skates, swimming) ones a week. In the control group patients will be asked to independently continue their regular physical activity same as prior to the oncologic treatment.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* women between 18 and 40 years of age, * with a known breast cancer, triple - negative or HER2 positive when the tumor size is ≥ 2cm and / or when cancer metastases to axillary lymph nodes or with luminal cancer at tumor size\> 3 cm are present, * qualified for preoperative chemotherapy, * ECOG 0-1, * correct left ventricular ejection fraction of at least 50% * correct results of laboratory tests for bone marrow, liver and kidney function (leukocytes ≥ 3 x 109 / l, neutrocytes ≥ 1.5 x 109 / l, hemoglobin ≥ 9 mg / dl \[5.59 mmol / l\], platelets ≥ 100 x 109 / l, AST / ALT ≤ 3 x ULN, bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 ULN).
Exclusion criteria
* diagnosis with cancer other than breast cancer in the last 5 years, except in situ melanoma, in situ cervical cancer, basal cell and squamous cell carcinoma. * other contraindications for planned systemic treatment: doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab. * Pregnant and breastfeeding patients. * Patients infected with HIV, HCV, HBV, after organ transplantation or suffering from an autoimmune disease requiring immunosuppressive treatment. If there are diseases of the musculoskeletal system or other, according to the doctor, preventing the patient from participating in the study or threatening her life and health if the planned intervention is used, the patient should not be included in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in tumor size | 1 year | Change in tumor size |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pathological response | 1 year | complete pathological response (pCR, pathologic Complete Response) |
| 3-yr DFS | 3 years | 3 years disease-free survival |
| overall survival | 5 years | OS - overall survival |
| Left Ventricle Ejection Fraction (LVEF) | 6 months | A change in LVEF \>10 percentage points, to a value below 50%. |
| Global Longitudinal Strain (GLS) | 6 months | A change in GLS \>15%. |
| high-sensitivity troponin | 6 months | Change above 95 percentile. |
| BNP | 6 months | For patients with acute onset dyspnea increase \<100 pg/ml, for patients with slow increase in breathlessness increase \>35 pg/ml. |
| Number of steps | 5 years | Daily number of steps measured throughout the intervention using an activity watch. |
| Daily calories burned | 5 years | Measured daily using an activity watch. |
| Kilometers passed | 5 years | Measured throughout the intervention using an activity watch. |
| Time spent actively | 5 years | Daily number of minutes spent actively measured using an activity watch. |
| Length of sleep | 5 years | Daily number of minutes of sleep measured using an activity watch. |
| Acceptance of illness | 5 years | Score based on Acceptance of Illness Scale, a single scale with range of points 8-40, with a higher score meaning better acceptance of one's medical condition. |
| Tumor microenvironment | 1 year | Assessment of the percentage of immune cells infiltrating the tumor based on immunohistochemical staining of paraffin sections of a tumor. Staining will include the following markers: CD45, CD8, CD4 to assess absolute inflammatory cells, cytotoxic T cells, and helper T cells. The infiltrating cells will be measured as an area occupied by inflammatory cells over total area, and will be expressed as a percentage. |
| Change in tumor ki67 level | 1 year | Ki67 will be assessed based on immunohistochemical staining of paraffine section of a tumor. Ki67 index will be measured as a number of ki67-positive cells over the total number of invasive cells, and will be expressed as a percentage. |
| Calories burned during physical activity | 5 years | Measured during physical activity using an activity watch. |
Other
| Measure | Time frame | Description |
|---|---|---|
| PRO-Quality of Life | 5 years | Score based on the QLQ-BR23 questionnaire which includes the following scales: body image (score range 4-16), sexual functioning (score range 2-8), systemic therapy side effects (score range 7-28), breast symptoms (score range 4-16), arm symptoms (score range 3-12), sexual enjoyment (score range 1-4), future perspectives (score range 1-4), being upset by hair loss (score range 1-4); higher score meaning worse outcome (higher level of symptomatology or lower level of functioning). |
Countries
Poland
Outcome results
None listed