Clinical trial NCT05057598: DianaWeb: Before and After Study Online Based Participatory Research on Breast Cancer Women
Official title: DianaWeb: Before and After Study Online Based Participatory Research to Test Whether Lifestyle and Diet Are Able to Reduce the Incidence of Recurrences (Local, Remote) or Secondary Cancers, Improve Prognosis and Survival of Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Breast cancer
Diet
Physical activity
Prognosis
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
Collaborators: name: University Of Perugia
name: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
name: Azienda Socio Sanitaria Territoriale di Mantova
name: Presidio Ospedaliero Unico "Santa Maria della Misericordia", Urbino
name: Ospedale Città di Castello- Perugia
name: University of Urbino "Carlo Bo"
name: Fondazione Vita e Salute
First posted: 2021-09-27
Enrollment: 50000
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Before and after study online based on community-based participatory research (CBPR): CBPR approach which has been defined as 'a process that involves community members or recipients of interventions in all phases of the research process'. Over the past two decades, there has been an increasing presence of community-based research and participatory methods in health research, and involving patients at various stages of the research process has been shown to improve the ethical nature of research and the appropriateness of methods.
Primary purpose: SUPPORTIVE_CARE

Brief summary: DianaWeb is a community-based participatory research (CBPR) offered to Italian breast cancer patients. The aim of the study is the evaluation of effectiveness of a lifestyle and nutrition intervention to improve the prognosis. DianaWeb study utilizes an interactive website - http://www.dianaweb.org/ - to monitor patient life-style, and to obtain clinical, pathological and anthropometric data (height, body weight, waist circumference and blood pressure). Detailed instructions were provided for measuring at home. The website contains theoretical and practical advice to encourage women to follow healthy lifestyles and nutrition, and the indications emerging from research for women diagnosed with breast cancer.

DianaWeb study intends to recruit 50.000 women with breast cancer diagnosis.

Detailed description: The investigators intend to carry out a participatory research on the influence of lifestyle after cancer diagnosis on the risk of recurrence. The investigators intend wake available to breast cancer survivors' evidence-based information on the effects of lifestyle on quality of life and prognosis and to invite and help them to adopt potentially preventive sustainable lifestyle changes. To improve the prognosis, the investigators will base the recommendations on the European Code Against Cancer 2014 (ECAC), on the World Cancer Research Fund 2018 (AICR/WCRF), Continuous Update Project (CUP) 2014 specific recommendations to breast cancer survivors, and on Mediterranean diet. As for the prevention of side effect of treatments there is no definitive evidence, but the daily exercise seems for reducing menopausal symptoms and osteoporosis, while regular consumption of food with diuretic effect for arthralgia due to aromatase inhibitors. The investigators are aware that the path for creating data to implementing evidence in routine practice is long and arduous. The investigators are confident, however, that engaging participants in the research process will enable many of participants to implement evidence-based practices in everyday life. The investigators, together with computer programmers, have developed an interactive website to build a large cohort of breast cancer survivors and to follow up participants about the impact of lifestyles and nutrition on recurrences, incidence of second breast cancer, metastasis, other cancers and other chronic diseases. The investigators will also monitor the prevalence of side effects of treatments (the investigators will focus on menopausal symptoms, arthralgia, osteoporosis and bone fractures). Observational epidemiological studies have consistently shown that sedentary lifestyle, overweight, metabolic syndrome, chronic inflammatory status, high glycemia and insulinemia, and a few specific dietary factors (low fibre and high saturated fat) are associated with poor breast cancer specific survival. There is ample room for reducing recurrences and cancer progression through lifestyles and nutrition. All these factors are clearly modifiable, but there is uncertainty, however, over whether voluntarily changing these factors after breast cancer diagnosis improve prognosis. In a 5 years' time the study after recruitment, the investigators are expected to confirm the prognostic role of this factors.

In Italy every year over 50.000 women develop breast cancer. The country is fairly well equipped with excellent breast cancer units and in the second decade of the twenty-first century 5-year breast cancer net survival reached 88%, a performance similar to the best European countries. Over 750.000 Italian women live with a previous diagnosis of breast cancer. Many of them with some form of cancer treatment and suffer from feeling left alone, fear of cancer recurrence and not receiving enough information and guidance after treatment: on prognosis, side effects of treatment, lifestyle strategies to help preventing side effects of treatments, recurrences and new primaries. Many survivors integrate adjuvant treatment with complementary treatments without scientific proof of efficacy, even with folk treatments that might increase the risk of recurrences.

Young women undergoing adjuvant breast cancer therapy experience a heavy impairment in important quality of life domains (anxiety, depression, loss or sexual desire, weight gain). The great majority of women under hormonal treatment experience an increase in the prevalence of menopausal symptoms and have sexual dysfunction that is distressing and difficult to resolve. In postmenopausal survivors with aromatase inhibitor-induced arthralgia the intensity of pain is associated with fear of recurrence.

Investigating whether lifestyle factors affect breast cancer patients' survival is a relatively new area of research, but there is growing evidence that the effect of modifiable anthropometric and metabolic factors may be of the same order of magnitude than the effect of the usual clinic-pathological risk factors.

Epidemiological evidence, even if based only on observational studies, suggest that lifestyle modification, including physical exercise and dietary habits, might have a strong impact on breast cancer patients overall and specific survival.

CUP have shown that:

1. overweight and obesity are associated with 10-20% increased risk of recurrences;
2. physical activity after diagnosis is associated with 30-40% reduction of recurrences and mortality;
3. soy food consumption is associated with lower risk
4. saturated fat consumption is associated with higher risk
5. higher consumption of foods containing fibre after diagnosis of primary breast cancer reduces risk of all-cause mortality Epidemiological studies have shown that modifiable lifestyle factors and biomarkers affecting the occurrence of breast cancer also affect breast cancer prognosis: obesity, metabolic syndrome, sedentary lifestyle, high fat intake, alcohol consumption, high fasting glucose plasma levels (independently of the presence of metabolic syndrome), clinical chronic inflammation, high plasma insulin and sex hormone levels, low sex hormone-binding protein.

Obesity is associated with a higher incidence of locally advanced disease, and worse prognosis after diagnosis, both before and after menopause.

The obesity is also related to poor quality of life and increased risk of developing comorbid conditions. Weight gain during and after cancer treatment also increases the risk of recurrence. Both chemotherapy and, to a lesser extent, tamoxifen and nonsteroidal aromatase inhibitors have been associated with weight gain. Among the potential mechanisms behind the association between weight gain, obesity, and breast cancer recurrence and mortality there is an increased conversion of androgens to oestrogens in peripheral adipose tissue and increased circulating levels of insulin, insulin-like growth factors (IGFs), and leptins, that promote tumour cell proliferation. Current breast cancer treatments can have a negative impact on cardiovascular health (left ventricular dysfunction, accelerated cardiovascular disease-CVD), and for women with pre-existing CVD, this might influence cancer treatment decisions by both the patient and the provider. Improvements in early detection and treatment of breast cancer have led to an increasing number of breast cancer survivors who are at risk of long-term cardiac complications from cancer treatments. Ideal breast cancer outcomes are reliant on coexisting cardiovascular health along the entire journey of breast cancer treatment. During breast cancer treatment, surveillance, prevention, and secondary management of cardiotoxicity are crucial; thereafter, long-term post-treatment monitoring for late cardiotoxicity and even non-treatment-related development of CVD is essential. Breast cancer and CVD share a number of common risk factors. Cardiovascular clinical care and research have focused on risk factors for \>60 years, because it is believed that 80% of CVD can be prevented through risk factor modifications such as promoting a healthy diet, physical activity, and a healthy weight; abstinence from tobacco; blood pressure control; diabetes mellitus management; and a good lipid profile. In women with breast cancer, treatment and the disease itself contribute to weight gain and to decreases in physical activity. Furthermore, it has been reported that cardiopulmonary function in patients with breast cancer improves with exercise, and regular exercise results in an improvement in quality of life. Although the usefulness of exercise to prevent CVD in patients with breast cancer has not been evaluated in randomized trials, it is reasonable to follow the recommendations for physical activity, that is, moderate-intensity aerobic physical activity of ≥30 minutes 5 days each week.

High fasting glycaemia, even within the normal range, is associated with higher incidence of recurrences. Also, the metabolic syndrome is associated with increased risk of breast cancer recurrences in patients diagnosed both before and after menopause and risk of developing distant metastasis than patients without any metabolic syndrome trait. Metabolic syndrome, also called insulin-resistance syndrome, is usually associated with high insulin and testosterone levels, and with clinical chronic inflammation. Independently of the presence of metabolic syndrome several studies have shown that breast cancer patients with high testosterone levels have worst prognosis. Insulin stimulates the synthesis of testosterone in the ovary, and high plasma insulin levels are associated with increased risk of recurrences. Insulin also increases the bioavailability of IGF-I (through the promotion of its liver synthesis and the inhibition of the synthesis of its binding proteins IGFBP-I) associated with prognosis in women with breast cancer. Also, high plasma levels of C-Reactive Protein (CRP), even within the normal range, are associated with increased risk of recurrence and shorter survival in patients with advanced breast cancer. It seems reasonable to hypothesize that a comprehensive lifestyle modification, based on AICR/WCRF and ECAC recommendations, consistent with traditional Mediterranean diet, may reduce the risk of recurrences and improve prognosis. Studies have shown that dietary intervention recommending a modified Mediterranean diet can reduce biological markers of breast cancer risk and recurrences: glycemia, insulinemia, IGF-I bioavailability and chronic inflammatory status. The Western dietary pattern, high in refined grains, sugars, simple carbohydrates, red meat, and high-fat dairy products, increases the levels of pro-inflammatory markers such as CRP and interleukin-6 (IL-6). In contrast, a traditional Mediterranean diet with consumption of whole grains cereals, pulses, vegetables, fruits, fish, nuts and extravirgin olive oil is associated with lower levels of pro-inflammatory biomarkers, including endothelial adhesion molecules, CRP, and tumor necrosis-α (TNF-α). Physical exercise also seems to reduce chronic inflammation. Furthermore, several studies have suggested a decrease of breast cancer recurrence and death in patients who exercise at least 30 min /day.

These information's are not currently available to patients and are not yet included in oncology protocols. With a few exceptions, physicians too are not aware of these scientific results and are not yet culturally prepared for life-style prescriptions. DianaWeb does not interfere with prescribed oncological treatments, on the contrary it recommends participants to follow the oncologist's prescriptions, but the study wants avoid the access to non-scientifically correct information that could worsen the prognosis or change the quality of life or health.

There is increasing interest, in the research community, in a community-based participatory research. Its relevance often is relegated to the "right end" of the research continuum, but may contribute also to asking the right questions, in particular the more relevant questions for the patients, to improve compliance, and to ensure that basic science research findings affect cancer outcomes in materially important ways especially for large communities that communicate through modern media as websites.

Eligibility criteria: Inclusion Criteria:

* Women with breast cancer diagnosis
* Women with breast cancer relapses
* Women with breast cancer metastases
* Women with breast cancer diagnosis even if many years have elapsed since the first diagnosis
* Women with breast cancer diagnosis and other tumors diagnosis
* Women with breast cancer diagnosis and other pathologists that impair cognitive abilities

Exclusion Criteria:

* Women with breast cancer diagnosis and clinical diagnosis of Alzheimer's Disease
* Women with breast cancer diagnosis and clinical diagnosis of dementia
* Women with breast cancer diagnosis unable to use personal computer and smart phone

Primary outcomes:
measure: Increase rate of survival
timeFrame: Baseline, 10 years
measure: Decrease incidence of relapses
timeFrame: Baseline, 10 years
measure: Decrease incidence of metastasis
timeFrame: Baseline, 10 years
measure: Decrease incidence of Metabolic Syndrome parameters
timeFrame: baseline, 1 year, 5 years, 10 years
measure: Decrease blood level on C-reactive protein (chronic inflammation marker)
timeFrame: baseline, 1 year, 5 years, 10 years
measure: Decrease the insulin resistance index (HOMA index)
timeFrame: baseline, 1 year, 5 years, 10 years
Secondary outcomes:
measure: Increase in the score of adherence to the Mediterranean diet score (MDS)
timeFrame: baseline, 1 year, 3 years, 5 years, 10 years
measure: Increase in the score of adherence to the Italian Mediterranean index (IMI)
timeFrame: baseline, 1 year, 3 years, 5 years, 10 years
measure: Increase in the score of adherence to the Mediterranean Adequancy index (MAI)
timeFrame: baseline, 1 year, 3 years, 5 years, 10 years
measure: Increase in the score of adherence to the AICR/WCRF recommendations to the 2018 WCRF/AICR News Score
timeFrame: baseline, 1 year, 3 years, 5 years, 10 years
measure: Increase in the score to the "European Organisation for Research and Treatment of Cancer, Quality of Life questionnaire-core 30 (Version 3.0)" after breast cancer diagnosis
timeFrame: baseline, 1 year, 3 years, 5 years, 10 years
measure: Increase in the score to the "European Organisation for Research and Treatment of Cancer, Quality of Life questionnaire-breast cancer 45 (QLQ-BR45)" during therapy
timeFrame: baseline, 1 year, 3 years, 5 years, 10 years
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione Irccs Istituto Nazionale Dei Tumori
state: MI
Study officials:
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
name: ANNA VILLARINI, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Natalucci V, Marini CF, Flori M, Pietropaolo F, Lucertini F, Annibalini G, Vallorani L, Sisti D, Saltarelli R, Villarini A, Monaldi S, Barocci S, Catalano V, Rocchi MBL, Benelli P, Stocchi V, Barbieri E, Emili R. Effects of a Home-Based Lifestyle Intervention Program on Cardiometabolic Health in Breast Cancer Survivors during the COVID-19 Lockdown. J Clin Med. 2021 Jun 17;10(12):2678. doi: 10.3390/jcm10122678.
citation: Natalucci V, Villarini M, Emili R, Acito M, Vallorani L, Barbieri E, Villarini A. Special Attention to Physical Activity in Breast Cancer Patients during the First Wave of COVID-19 Pandemic in Italy: The DianaWeb Cohort. J Pers Med. 2021 May 6;11(5):381. doi: 10.3390/jpm11050381.
citation: Gianfredi V, Nucci D, Balzarini M, Acito M, Moretti M, Villarini A, Villarini M. E-Coaching: the DianaWeb study to prevent breast cancer recurrences. Clin Ter. 2020 Jan-Feb;170(1):e59-e65. doi: 10.7417/CT.2020.2190.
citation: Villarini M, Acito M, Gianfredi V, Berrino F, Gargano G, Somaini M, Nucci D, Moretti M, Villarini A. Validation of Self-Reported Anthropometric Measures and Body Mass Index in a Subcohort of the DianaWeb Population Study. Clin Breast Cancer. 2019 Aug;19(4):e511-e518. doi: 10.1016/j.clbc.2019.04.008. Epub 2019 Apr 18.
citation: Villarini M, Lanari C, Nucci D, Gianfredi V, Marzulli T, Berrino F, Borgo A, Bruno E, Gargano G, Moretti M, Villarini A. Community-based participatory research to improve life quality and clinical outcomes of patients with breast cancer (DianaWeb in Umbria pilot study). BMJ Open. 2016 Jun 1;6(6):e009707. doi: 10.1136/bmjopen-2015-009707.