Effects of Diet and Osteopathy on Quality of Life and Inflammation in Breast Cancer Patients Under Hormonal Therapy

Study Overview
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Brief Summary
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Breast cancer patients under hormonal therapy may experience significant adverse events related to this treatment and as a result, failure to adhere to adjuvant therapies or discontinuation of treatment has been reported to be high. Promoting weight control and the adoption of healthy lifestyle habits in breast cancer survivors has an impact on hormonal status, quality of life and physical functioning, contributing to reduce cancer recurrence risk, cancer-related and chronic-condition-related mortality. Manipulation procedures, such as manual treatment with osteopathic techniques, have positive effects on osteoarticular pain, peripheral neuropathies, anxious-depressive disorders, asthenia and sleep disorders, also improving immune and neuroendocrine responses. The aim of this study is to evaluate the effects of dietary intervention and manual treatment with osteopathic techniques in women diagnosed with breast cancer under antiestrogenic hormonal treatment through the assessment of: modifications of quality of life (QoL) frequency and severity of symptoms related to antiestrogenic hormonal treatment body weight body composition food habits metabolic and inflammatory state physical performance patient's satisfaction to multidisciplinary treatment. This study focuses on patient's centricity evaluating the effects that long lasting adjuvant therapies have on breast cancer survivors. Improving personalized patient's treatment through collaborative interactions between clinicians, osteopaths and nutrition specialists might result in implementation strategies to determine novel evidence-based treatments for ameliorating patient's adherence to oncological therapies, impacting prognosis and survival.

Detailed Description
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Breast cancer patients under hormonal therapy may experience significant adverse events related to this treatment. Premenopausal women may encounter the classic symptoms of menopausal syndrome: hair thinning or loss; hot flashes, sweating, fatigue, insomnia, joint pain, vaginal dryness, decreased libido, anxious-depressive disorders, cognitive dysfunction; dry eyes; weight gain. Postmenopausal women may instead experience joint stiffness and joint pain, depressive and anxious symptoms, fatigue and irritability. Since most of these adverse events do not resolve spontaneously a few weeks/months after starting treatment, they often negatively impact patient's quality of life. As a result of treatment-related adverse events, failure to adhere to adjuvant therapies or discontinuation of treatment has been reported to be high and this may negatively impact patient's prognosis and survival. Patients with breast cancer frequently experience weight gain during and after adjuvant hormonal treatment. Indeed, menopause, musculoskeletal pain and the consequent physical activity reduction, work together to reduce the basal energy metabolism. On the other side, the psychological distress and the eventual use of food for emotional reward, do promote weight gain. Notably, breast cancer patients who are overweight or obese show an increased risk of overall mortality, cancer-specific mortality, breast cancer relapse or second primary contralateral breast cancer. The explanation lies in the fact that the increase in fat mass is directly correlated to an increased production of estrogens, insulin, leptin and proinflammatory cytokines which, all together, exhibit a mitogenic activity on mammary cells. Proinflammatory cytokines and insulin deregulation on their turn, favor with time the onset of other chronic diseases such as diabetes, dyslipidemia, metabolic syndrome in general, thus increasing the risk of overall mortality. Conversely, weight loss can improve hormonal status, quality of life and physical functioning and contribute to reduce cancer recurrence risk, cancer-related and chronic-condition-related mortality. Therefore, it is important to promote weight control and the adoption of healthy lifestyle habits in breast cancer survivors. Manipulation procedures, such as manual treatment with osteopathic techniques, involve the mechanical displacement of fluids and the removal of toxic substances with neurovascular and neuromuscular effects, thus producing positive alterations at the metabolic, biochemical and circulatory level. Several studies conducted on patients with breast cancer have supported the positive effect of manual therapy (acupuncture, shiatsu treatments, massages) on the control of various problems such as osteoarticular pain, peripheral neuropathies, anxious-depressive disorders, asthenia and sleep disorders, also improving immune and neuroendocrine responses. Nevertheless, there are no studies on the effect of manual treatment with osteopathic techniques on the control of symptoms related to the side effects induced by anti-tumor therapies. The aim of this study is to evaluate the effects of dietary intervention and manual treatment with osteopathic techniques in women diagnosed with breast cancer under antiestrogenic hormonal treatment through the assessment of: modifications of quality of life (QoL) frequency and severity of symptoms related to antiestrogenic hormonal treatment body weight body composition food habits metabolic and inflammatory state physical performance patient's satisfaction to multidisciplinary treatment. This study focuses on patient's centricity evaluating the effects that long lasting adjuvant therapies have on breast cancer survivors. Improving personalized patient's treatment through collaborative interactions between clinicians, osteopaths and nutrition specialists might result in implementation strategies to determine novel evidence-based treatments for ameliorating patient's adherence to oncological therapies, impacting prognosis and survival.

Official Title
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A Randomised Effectiveness-implementation Trial for Evaluating Dietary and Manual Treatment With Osteopathic Techniques on Quality of Life and on Modulation of the Inflammatory State of Patients Diagnosed With Breast Cancer Undergoing Antiestrogenic Hormonal Treatment.

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: manual treatment with osteopathic techniques and nutritional treatment
* Other: manual treatment with osteopathic techniques
* Other: nutritional treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Voluntary written informed consent Histologically confirmed estrogen receptor-positive invasive breast cancer or in situ breast cancer after breast surgery Absence of locoregional relapse or distant metastasis Premenopausal or postmenopausal status Hormonal therapy with tamoxifen and/or LHRH analogues or aromatase inhibitors Patients with or without neoadjuvant or adjuvant chemotherapy Patients with a BMI > 18.5 kg/m^2 Absence of language barrier Exclusion Criteria: Previous hormonal therapy Use of medical treatments that contrast adjuvant hormonal therapy adverse effects (e.g. menopausal symptoms and arthralgia). Underweight patients (BMI <18.5 kg/m^2) Patients diagnosed with eating disorders (e.g. anorexia nervosa, bulimia, binge eating, orthorexia) Psychiatric disorders or cognitive impairments Previous malignancies other than in situ cervical carcinoma or non-melanoma skin cancer Non-epithelial breast cancer at histological examination In situ lobular breast cancer Participation in other randomized clinical trials that could interfere with current study Patients living distant from trial center and unable to attend for check-ups and meetings.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: This is an hybrid type I eﬀectiveness-implementation trial, testing the effectiveness of clinical therapeutic interventions, coupled by exploration of the eﬀects of the implementation of the effective intervention(s) in clinical practice (professional practice changes, changes in processes of care, quality of intervention delivery, patient's satisfaction). The effectiveness study will be a before-and-after randomized trial performed according to a 2 × 2 factorial design. Two groups are identified: Group A: Premenopausal breast cancer patients treated with tamoxifen and/or luteinizing hormone-releasing hormone (LHRH) analogues. Group B: Postmenopausal breast cancer patients treated with aromatase inhibitors. Patients in each group will be randomly assigned to four treatments arms: Arm 1, manual treatment with osteopathic techniques and nutritional treatment. Arm 2, manual treatment with osteopathic techniques. Arm 3, nutritional treatment. Arm 4, control.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1: manual treatment with osteopathic techniques and nutritional treatment in premenopausal patients<br>Premenopausal breast cancer patients under tamoxifen and/or LHRH analogues are treated with manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques) and nutritional treatment (personalized Mediterranean Diet). | Other: manual treatment with osteopathic techniques and nutritional treatment<br>* manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques) and nutritional treatment (personalized Mediterranean Diet)<br>|
| Experimental: A2: manual treatment with osteopathic techniques in premenopausal patients<br>Premenopausal breast cancer patients under tamoxifen and/or LHRH analogues are treated with manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques). | Other: manual treatment with osteopathic techniques<br>* manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques)<br>|
| Experimental: A3: nutritional treatment in premenopausal patients<br>Premenopausal breast cancer patients under tamoxifen and/or LHRH analogues are treated with nutritional treatment (personalized Mediterranean Diet). | Other: nutritional treatment<br>* nutritional treatment (personalized Mediterranean Diet)<br>|
| No Intervention: A4: control group in premenopausal patients<br>Premenopausal breast cancer patients under tamoxifen and/or LHRH analogues receive general counselling on healthy dietary habits and lifestyle in accordance to the World Cancer Research Fund (WCRF) guidelines. | |
| Experimental: B1: osteopathic techniques and nutritional treatment in postmenopausal patients<br>Postmenopausal breast cancer patients under aromatase inhibitors are treated with manual treatment (8 once-a-week manual treatments with osteopathic techniques) and nutritional treatment (personalized Mediterranean Diet). | Other: manual treatment with osteopathic techniques and nutritional treatment<br>* manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques) and nutritional treatment (personalized Mediterranean Diet)<br>|
| Experimental: B2: manual treatment with osteopathic techniques in postmenopausal patients<br>Postmenopausal breast cancer patients under aromatase inhibitors are treated with manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques). | Other: manual treatment with osteopathic techniques<br>* manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques)<br>|
| Experimental: B3: nutritional treatment in postmenopausal patients<br>Postmenopausal breast cancer patients under aromatase inhibitors are treated with nutritional treatment (personalized Mediterranean Diet). | Other: nutritional treatment<br>* nutritional treatment (personalized Mediterranean Diet)<br>|
| No Intervention: B4: control group in postmenopausal patients<br>Postmenopausal breast cancer patients under aromatase inhibitors receive general counselling on healthy dietary habits and lifestyle in accordance to the World Cancer Research Fund (WCRF) guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the effect of dietary intervention and manual treatment with osteopathic techniques on quality of life (QoL) of women diagnosed with breast cancer under hormonal treatment | Quality of life will be assessed using the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire comparing the before-and-after treatment difference in FACT-ES QoL scale (range 0-200; the higher the FACT-ES score, the better the quality of life, QoL) evaluated at baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3). The difference between pre treatment (baseline, T0) score and 24-weeks (six months, T2) score of the FACT ES QoL scale will be analyzed by ANOVA, and the interaction between the dietetic treatment and manual treatment with osteopathic techniques will be tested at 5% significance level. In a secondary ANOVA analysis, the baseline-to-52-weeks (T3) follow-up difference of the FACT ES QoL scale scores will additionally be analyzed. These analyses will be conducted separately in Groups A and B. | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related adverse events of hormonal treatment in premenopausal and postmenopausal patients | Symptoms related to hormonal treatment will be evaluated using Menopause Rating Scale (MRS) (range 0-44; higher scores indicating worse symptoms) in Group A and EORTC Quality of Life Questionnaire - Breast Cancer Module (EORTC-QLQ-C30/BR23) (range 0-100; higher scores corresponding to worse symptoms) in Group B, respectively. | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Body weight | Body weight will be evaluated using body mass index (BMI), measuring weight in kilograms divided by the square of height in meters. | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Body composition | Body composition will be evaluated combining two anthropometric measures: the waist circumference (cm) and calf circumference (cm). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Food habits | Food habits will be assessed through a food frequency questionnaire. | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Hemoglobin | Hemoglobin will be assessed collecting blood exams measuring hemoglobin levels (g/dL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Red blood cells | Red blood cells will be assessed collecting blood exams measuring red blood cells count (cells/mcL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Platelets | Platelets will be assessed collecting blood exams measuring platelets count (cells/mcL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| White blood cells | White blood cells will be assessed collecting blood exams measuring white blood cells count (cells/mcL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Lymphocytes | Lymphocytes will be assessed collecting blood exams measuring lymphocytes count (cells/mcL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Monocytes | Monocytes will be assessed collecting blood exams measuring monocytes count (cells/mcL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Neutrophils | Neutrophils will be assessed collecting blood exams measuring neutrophils count (cells/mcL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Inflammatory state: erythrocyte sedimentation rate | inflammatory state will be assessed collecting blood exams measuring erythrocyte sedimentation rate (ESR) (mm/h) | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Vitamin D | Vitamin D will be assessed collecting blood exams measuring Vitamin D levels (ng,mL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Metabolic state: plasma glycemia | Metabolic state will be assessed collecting blood exams measuring plasma glycemia (mg/dl) | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Metabolic state: serum insulin concentration | Metabolic state will be assessed collecting blood exams measuring serum insulin concentration (µU/ml). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Metabolic state: total cholesterol | Metabolic state will be assessed collecting blood exams measuring total cholesterol (mg/dL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Metabolic state: low-density lipoprotein (LDL) cholesterol | Metabolic state will be assessed collecting blood exams measuring low-density lipoprotein (LDL) cholesterol (mg/dL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Metabolic state: high-density lipoprotein (HDL) cholesterol | Metabolic state will be assessed collecting blood exams measuring high-density lipoprotein (HDL) cholesterol (mg/dL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Metabolic state: triglycerides | Metabolic state will be assessed collecting blood exams measuring triglycerides (mg/dL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Inflammatory state: c-reactive protein (CRP) | inflammatory state will be assessed collecting blood exams measuring c-reactive protein (CRP) (mg/L). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Sex hormone binding globulin (SHBG) | Sex hormone binding globulin (SHBG) will be assessed collecting blood exams measuring sex hormone binding globulin levels (SHBG) (nmol/L). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Inflammatory state: Interleukin-6 (IL-6) | inflammatory state will be assessed collecting blood exams measuring Interleukin-6 (IL-6) levels (pg/mL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Inflammatory state: Tumour necrosis factor-α (TNF-α) | inflammatory state will be assessed collecting blood exams measuring Tumour necrosis factor-α (TNF-α) levels (pg/ml). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Testosterone | Testosterone levels will be assessed collecting blood exams measuring testosterone levels (ng/dL). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Modifications of blood lipid profile | modifications of blood lipid profile will be assessed collecting blood exams measuring plasma lipids by UPLC-MS. | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Physical performance | Physical performance will be assessed using International Physical Activity Questionnaires (IPAQ) measuring physical activity levels (higher scores indicating higher physical activity). | baseline (T0), after 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 
| Patient's satisfaction to multidisciplinary treatment | Patient's satisfaction to multidisciplinary treatment will be assessed with Functional Assessment of Chronic Illness Therapy - Treatment Satisfaction - General questionnaire (FACIT-TS-G) (range 0-25; the higher the score, the better the satisfaction). | 12 weeks (T1), after 24 weeks (T2) and after 52 weeks (T3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hormonal therapy, treatment-related adverse events, osteopathic techniques, diet, quality of life