Neoplasms

Skin and Connective Tissue Diseases

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Symptoms and General Pathology

Behaviors and Mental Disorders

Breast Neoplasms

Inflammation

Breast Diseases

Skin Diseases

Quality of Life

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Aromatase Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

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).

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).

Premenopausal breast cancer patients under tamoxifen and/or LHRH analogues are treated with nutritional treatment (personalized Mediterranean Diet).

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.

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).

Postmenopausal breast cancer patients under aromatase inhibitors are treated with manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques).

Postmenopausal breast cancer patients under aromatase inhibitors are treated with nutritional treatment (personalized Mediterranean Diet).

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.

manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques) and nutritional treatment (personalized Mediterranean Diet)

manual treatment with osteopathic techniques and nutritional treatment

manual treatment with osteopathic techniques (8 once-a-week manual treatments with osteopathic techniques)

manual treatment with osteopathic techniques

nutritional treatment (personalized Mediterranean Diet)

nutritional treatment

Cristina Ferraris, MD

Chiara Listorti, MD

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.

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.

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.

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

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.

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.

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.

Body weight will be evaluated using body mass index (BMI), measuring weight in kilograms divided by the square of height in meters.

Body composition will be evaluated combining two anthropometric measures: the waist circumference (cm) and calf circumference (cm).

Food habits will be assessed through a food frequency questionnaire.

Hemoglobin will be assessed collecting blood exams measuring hemoglobin levels (g/dL).

Red blood cells will be assessed collecting blood exams measuring red blood cells count (cells/mcL).

Platelets will be assessed collecting blood exams measuring platelets count (cells/mcL).

White blood cells will be assessed collecting blood exams measuring white blood cells count (cells/mcL).

Lymphocytes will be assessed collecting blood exams measuring lymphocytes count (cells/mcL).

Monocytes will be assessed collecting blood exams measuring monocytes count (cells/mcL).

Neutrophils will be assessed collecting blood exams measuring neutrophils count (cells/mcL).

inflammatory state will be assessed collecting blood exams measuring erythrocyte sedimentation rate (ESR) (mm/h)

Vitamin D will be assessed collecting blood exams measuring Vitamin D levels (ng,mL).

Metabolic state will be assessed collecting blood exams measuring plasma glycemia (mg/dl)

Metabolic state will be assessed collecting blood exams measuring serum insulin concentration (µU/ml).

Metabolic state will be assessed collecting blood exams measuring total cholesterol (mg/dL).

Metabolic state will be assessed collecting blood exams measuring low-density lipoprotein (LDL) cholesterol (mg/dL).

Metabolic state will be assessed collecting blood exams measuring high-density lipoprotein (HDL) cholesterol (mg/dL).

Metabolic state will be assessed collecting blood exams measuring triglycerides (mg/dL).

inflammatory state will be assessed collecting blood exams measuring c-reactive protein (CRP) (mg/L).

Sex hormone binding globulin (SHBG) will be assessed collecting blood exams measuring sex hormone binding globulin levels (SHBG) (nmol/L).

inflammatory state will be assessed collecting blood exams measuring Interleukin-6 (IL-6) levels (pg/mL).

inflammatory state will be assessed collecting blood exams measuring Tumour necrosis factor-α (TNF-α) levels (pg/ml).

Testosterone levels will be assessed collecting blood exams measuring testosterone levels (ng/dL).

modifications of blood lipid profile will be assessed collecting blood exams measuring plasma lipids by UPLC-MS.

Physical performance will be assessed using International Physical Activity Questionnaires (IPAQ) measuring physical activity levels (higher scores indicating higher physical activity).

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).

Spots Global Cancer Trial Database for manual treatment with osteopathic techniques and nutritional treatment