Breast Cancer InvasiveDIANA-5NCT05019989
Trial of Diet, Physical Activity and Breast Cancer Recurrences: the DIANA-5 Study
A study testing Intervention group on diet and physical activity in people with Breast Cancer Invasive, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
Trial summary
The investigators recruited 1542 Breast Cancer (BC) patients and to randomize the participants in two groups: 773 have received standard recommendations for healthy lifestyle without, however, any active support; 700 have received a combination of individual and group contacts over the course of one year, including… Read more about this study
- Who is it for?
- Ages 35 to 70 years, women only
- Conditions the study is for
- Breast Cancer Invasive
- What is being tested?
- Intervention group on diet and physical activity
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,542 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2008to 30 Sep 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mastectomy or conservative surgery for invasive breast cancer, any type, in the last five years (the investigators recruited mostly patients at the time or after surgery, when chemotherapy has been concluded and hormonal therapy, if necessary, has been started)
- Absence of signs or symptoms suggestive of recurrences
- Presence of one or more of the following endocrine/metabolic indicators: serum testosterone level ≥ 0.4 ng/ml (1 nmol/ml), corresponding to the median value in BC patients, or serum insulin ≥ 50 pmol/L, corresponding to the upper quartile of insulin distribution in Breast Cancer patients, or metabolic syndrome, present in about 15% of Breast Cancer patients.
Who cannot join
- Metastatic disease or previous relapse
- Age >70
- Physical or mental handicaps that would have impeded to engage in moderate physical activity or participate in kitchen classes
About this study
Official title: DIANA-5: Randomized Trial to Test the Efficacy of Dietary Change and Physical Activity to Prevent or Delay the Development of Recurrences in Breast Cancer Patients Estimated to be at High Risk of Recurrence Hormonal and Metabolic Reasons
The investigators recruited 1542 Breast Cancer (BC) patients and to randomize the participants in two groups: 773 have received standard recommendations for healthy lifestyle without, however, any active support; 700 have received a combination of individual and group contacts over the course of one year, including kitchen courses, gym and dance classes, common meals and reinforcing meetings, with emphasis on a comprehensive dietary change including low saturated fat and low refined carbohydrates, and high whole grain cereals and pulses consumption. Compliance have been monitored through weight change and plasma glucose, triglycerides, cholesterol and testosterone.
The main analysis will be by intention to treat. Under the hypothesis of reducing recurrence rate by 25% or 33% the statistical power of the study is 80% or, respectively, 90%, (P<0.05, 5-year follow-up).
Read the detailed description
Aims The investigators have been proposing a randomized intervention trial of diet and physical activity to reduce BC relapse (local, distant), and second ipsilateral or contralateral BC risk, in BC patients at high metabolic-endocrine of recurrence risk.
Secondary aims:
- to evaluate the effect of the combined dietary and physical activity change on the prevalence of Metabolic Syndrome
- to evaluate the effect of the combined dietary and physical activity change on the prevalence on risk biomarkers (BMI > 24.9 kg/m^2)
- to evaluate the effect of the combined dietary and physical activity change on the prevalence on risk biomarkers (testosterone >= 0.4 ng/ml)
- to evaluate the effect of the combined dietary and physical activity change on the prevalence on risk biomarkers (insulin > pmol/l)
- to evaluate the effect of the intervention on the development of other life-style related health conditions (other cancers, diabetes, hypertension, dyslipidemia, total mortality)
Recruitment:
Potential participants have been recruited at the time of diagnosis through follow-up clinics, patients' associations, or the media. Patients have been requested to sign an informed consent, including authorization for getting blood samples, for storing samples for future studies. The investigators collected demographic information, fasting measure body weight, height, waist circumference, and blood pressure, blood glucose, LDL and HDL cholesterol, triglycerides, testosterone and insulin. Eligible patients have filled in a baseline questionnaire on medical history, medication use, reproductive and body weight history, usual physical activity, and a validated semi-quantitative food frequency questionnaire.
Biological bank: the investigators collected and stored at -80°C one aliquot of whole blood, three 2-ml serum aliquot and two 2-ml buffy coat aliquot.
Randomization:
The investigators recruited 1542 patients' high risk and randomized the participants in two groups: 773 (control group) have received general standard written recommendation for healthy lifestyle without, however, any active support; 770 (intervention group) have received a combination of individual and group contacts over the course of one year, including kitchen courses, gym and dance classes, common meals and reinforcing meetings, with emphasis on a comprehensive dietary and life-style change.
Randomization has been carried out within strata of age, treatment (no adjuvant therapy, chemotherapy only, hormonal therapy only, both hormonal and chemotherapy) and axillary nodal status at diagnosis.
Patients who did not satisfy the high-risk criteria have been given the same general recommendations as the control group, and have been followed up as an external low risk group.
Intervention:
The intervention wanted aim to increase physical activity, controlling weight, and promoting healthy diet.
- Physical activity: achieve and maintain regular participation in a moderate intensity physical activity program of 210 minutes/week (30 min on average per day) over at least 3 days /week; decrease sedentary behaviors by 30 minutes/day on at least 5 days/week. During the first 12 months one group physical activity session per month offered to enhance program adoption. Women who wanted to take up vigorous sports encouraged to do so. For those who do not progressed to more vigorous activity, the focus was on maintaining moderate activities, such as walking. For self-monitoring and compliance enhancement, study participants had use logs, fill-in questionnaires and armband to monitor physical activity.
- Weight control: reducing energy intake relative to expenditure was the primary dietary focus for promoting weight loss in overweight or obese participants, while maintaining a healthy energy balance was the primary focus for normal weight participants. Participants were encouraged to include whole grains, pulses and high-fiber vegetables.
- Healthy diet: reducing calorie intake, through the preferred consumptions of highly satiating foods, such as unrefined cereals, legumes and vegetables, reducing high glycemic index food, high insulinemic foods, saturated fat, preferring instead unrefined vegetable fats, such as extra virgin olive oil, nuts and oleaginous seeds, reducing protein intake, mainly animal protein (except fish).
Baseline and yearly measurements:
Height and weight: electronic scale with women in light clothes and without shoes. In a sample of cases body fat and lean mass will be measured with bioelectric impedance (BIA).
Blood pressure: electronic device. Serum glucose, triglycerides and cholesterol: standard quality-controlled laboratory techniques.
Serum Testosterone and Insulin: Radioimmunoassay (RIA). For testosterone the investigators have used a direct RIA kit which has been validated by comparison with indirect assay after organic extraction of serum samples and celite purification.
Compliance:
Compliance has been monitored through lifestyle questionnaires, dietary questionnaires, weight change and plasma glucose, triglycerides, cholesterol, insulin, testosterone changes after one year of intervention. A compliance score has been computed, based on the direction of change in all these biomarkers.
Follow-up and outcome events:
The main outcome is the new BC events including:
- new primary breast cancer
- local/regional recurrence
- distant/metastatic recurrence The follow up have been based on the routine clinical follow-up at the collaborating hospitals, the periodic questionnaires to study participants, the regional cancer registry and hospital discharge diagnosis system, and death certificates.
Statistical power:
The survival of BC patients in Italy is dramatically increasing: 5-year relative survival increased from 80.6% for patients diagnosed in the early 1990s to 85.6% for patients diagnosed in the early 2000s. For these patients the estimated relapse free survival is 81.9. Such a survival improvement is accompanied by a postponement of the incidence of relapse.
The original aim was to recruit 1,200 high risk patients in order to have 600 patients per arm, which shall guarantee 80% chance of getting a significant difference also with 25% reduction, and allowing for 90% compliance in the intervention group and 10% contamination of the control group.
Statistical analysis:
Nowadays the investigators are assessing the baseline association between androgens, insulin, and several measures of adiposity including body mass index (BMI), waist circumference and percentage body fat, through Spearman correlation coefficients. Furthermore, the investigators are comparing the change in food consumption, body weight, and geometric means of hormones end points from baseline to 12 months in the intervention and control group.
The main analysis of the intervention effect on the incidence of recurrences is by intention to treat, i.e. based on assigned treatment at the time of randomization, regardless of adherence. Later, as a secondary analysis the investigators shall assess the effect by change in body weight and biomarkers. The investigators shall compute total survival and disease-free survival.
Hazard ratios and confidence intervals will be computed by the Cox proportional hazard model, with standard clinic-pathological prognostic covariates as potential confounders. Separate analyses will be carried out by Estrogen Receptors, Progesterone Receptors and erbB2 status. The investigators decided to carry out another follow-up in 2022 as the relapse time has lengthened to 10 years, due to new therapies, and to evaluate the effects on lifestyle due to closures during the pandemia severe acute respiratory syndrome-CoV-2.
Feasibility:
The principal investigator (at first dr. Franco Berrino and later dr. Anna Villarini) has long term experience in carrying on and coordinating epidemiological studies, including small-scale dietary intervention studies. The Milano National Cancer Institute and the others collaborating center is fully equipped with facilities for kitchen courses and gym facilities.
Control of potential biases:
Performance bias-patients have been recruited after the main treatments have been planned or delivered. In no case the allocation to the intervention or control group or the compliance will affect treatment.
Measurement bias-patients and researchers cannot be blinded, but the ascertainment of outcome was carried out by clinicians that were not involved in the study.
Attrition bias-Based on previous studies the investigators expect a fairly high compliance in the intervention group (>90%) but also some modification in the control group. After the main analysis by intention to treat, therefore, secondary analyses will be carried out by compliance score.
- Conditions
- Breast Cancer Invasive
- Being tested
- Intervention group on diet and physical activity, Control group: only public recommendation an lifestyle
- Keywords
- Breast cancer, Diet, Physical activity, Recurrences
- Medical subject headings
- Breast Neoplasms, Motor Activity, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intervention group on diet and physical activityBehavioural
The intervention wanted to increase physical activity, controlling weight, promoting healthy diet.
- Physical activity: achieve and maintain regular participation in a moderate intensity physical activity program of 210 minutes/week (30 min on average per day) over at least 3 days /week; decrease sedentary behaviors by 30 minutes/day on at least 5 days/week
- Weight control: reducing energy intake relative to expenditure is the primary dietary focus for promoting weight loss in overweight or obese participants, and maintaining a healthy energy balance is the primary focus for normal weight participants. Participants will be encouraged to include whole grains and high-fiber vegetables
- Healthy diet: reducing calorie intake, through the preferred consumptions of unrefined cereals, pulses and vegetables, reducing high glycemic index food and high insulinemic foods, such as sugar and milk; reducing sources of saturated fat and animal protein (except fish)
Control group: only public recommendation an lifestyleBehavioural
- Invitation leaflet, explaining the rationale of the study and including basic life-style recommendations, based on the 1997 World Cancer Research Fund recommendations (to be updated in 2007) and the Italian National Institute of Nutrition food pyramid.
- Dissemination of the information on the study by media
- Yearly follow-up questionnaire on breast events and dietary and physical activity chang
| Study group | Role | What they receive |
|---|---|---|
| Intervention group: on diet and physical activity | Experimental | Individual advice on diet and on physical activity Kitchen courses to teach basic Mediterranean and macrobiotic recipes (two 1-day course plus ten 3-h courses associated with common dinner) (15-20 participants at a time) Fortnightly common lunch or dinner (50-60 participant at a time) Basic gymnastic course (twelve - monthly- 2-hour courses)
* Study newsletter, with scientific information, kitchen recipes, study facilities
* Periodic conferences on diet and health
* Periodic reinforcement meetings with common meals, gymnastic sessions, and dancing, after the first year
* Periodic body weight assessment (weekly self-measurement and monthly measurement at the study center)
* Discounted rate for advanced kitchen courses
* Psychological support groups Receives: Behavioral: Intervention group on diet and physical activity |
| Control group: only public recommendations on lifestyle | Experimental | 1. Invitation leaflet, explaining the rationale of the study and including basic life-style recommendations, based on the 1997 World Cancer Research Fund recommendations (to be updated in 2007) and the Italian National Institute of Nutrition food pyramid.
2. Dissemination of the information on the study by media
3. Yearly follow-up questionnaire on breast events and dietary and physical activity chang Receives: Behavioral: Control group: only public recommendation an lifestyle |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of recurrences
The investigators have been proposing a randomized intervention trial of diet and physical activity to change BC relapse (local, distant), and second ipsilateral or contralateral BC, in BC patients at high risk of recurrence because of biochemical markers of increased risk, namely high serum testosterone and/or high fasting insulin and/or metabolic syndrome. Several other markers of increased recurrence risk are available, such as cancer stage at diagnosis, histological grade, hormonal receptors and other gene expression profile. All these will be registered, but the investigators are specifically interested in markers of the host that can be modified through life-style.
Measured: Baseline, fifth year
Secondary outcomes (7)
Modification lifestyle and Metabolic Syndrome (MetS)
The effect of the combined dietary and physical activity change on the prevalence of MetS (defined as the presence of three or more risk factors: waist circumference >85 cm, systolic blood pressure >130 mmhg and /or diastolic blood pressure >85 mmhg), glycaemia >100mg/100ml, triglycerides >150 mg/100ml or HDL cholesterol <50 mg/100ml) that is hypothesized to be intermediate factor in the association of diet and physical activity with BC recurrences.
Measured: Baseline, first year
Modification lifestyle and Body Mass Index (BMI)
The effect of the combined dietary and physical activity change on the prevalence on risk biomarkers (BMI > 24.9 kg/m^2) that is hypothesized to be intermediate factors in the association of diet and physical activity with BC recurrences.
Measured: Baseline, first year
Modification lifestyle and Testosterone
The effect of the combined dietary and physical activity change on the prevalence on risk biomarkers (testosterone >= 0.4 ng/ml) that is hypothesized to be intermediate factors in the association of diet and physical activity with BC recurrences.
Measured: Baseline, first year
Modification lifestyle and Insulin
The effect of the combined dietary and physical activity change on the prevalence on risk biomarkers (insulin > 50 pmol/L) that is hypothesized to be intermediate factors in the association of diet and physical activity with BC recurrences.
Measured: Baseline, first year
Development other cancer
The effect of the intervention on the incidence of other cancers in all patients through the medical history reported in the medical record
Measured: Baseline, fifth year
Development diabetes
The effect of the intervention on the incidence of diabetes in all patients through the medical history reported in the medical record
Measured: Baseline, fifth year
Total mortality
The effect of the intervention on total mortality in all patients through the reference oncologists
Measured: Baseline, fifth year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2021
- Study start1 Jun 2008
- Primary completion30 Sep 2012
- Study completion30 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer InvasiveStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Trial of Diet, Physical Activity and Breast Cancer Recurrences. The investigators recruited 1542 patients' high risk and randomized them in two groups: 773 (control group) have received general standard written recommendation for healthy lifestyle without, however, any active support; 769 (intervention group) have received a combination of individual and group contacts over the course of one year, including kitchen courses, gym and dance classes, common meals and reinforcing meetings, with emphasis on a comprehensive dietary and life-style change.
- Masking
- None (open label)
- Enrolment
- 1,542 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Associazione Italiana per la Ricerca sul Cancro, European Institute of Oncology, Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte, Federico II University, IRCCS Cancer Referral Center of Basilicata, ARNAS Civico Di Cristina Benfratelli Hospital, Lega Italiana per la Lotta contro i Tumori, Azienda Socio Sanitaria Territoriale di Mantova, Ministero della Salute, Italy
- Responsible party
- Principal investigator, Anna Villarini, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Investigators
- ANNA VILLARINI, PhD, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05019989
- Sponsor's protocol ID
- INT 37/07
- Acronym
- DIANA-5
- Status last verified
- Aug 2021
- First submitted
- 14 Jul 2021
- Last updated
- 25 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study protocol, dataset, statistical analysis plan, informed consent form and clinical study report were discussed through meetings held with all the collaborating centers. The individual participant data (IPD) were delivered to the coordinators of the individual centers in coded anonymous.
Publications
Roveda E, Bruno E, Galasso L, Mule A, Castelli L, Villarini A, Caumo A, Esposito F, Montaruli A, Pasanisi P. Rest-activity circadian rhythm in breast cancer survivors at 5 years after the primary diagnosis. Chronobiol Int. 2019 Aug;36(8):1156-1165. doi: 10.1080/07420528.2019.1621330. Epub 2019 Jun 10.
PubMed 31177874Roveda E, Vitale JA, Bruno E, Montaruli A, Pasanisi P, Villarini A, Gargano G, Galasso L, Berrino F, Caumo A, Carandente F. Protective Effect of Aerobic Physical Activity on Sleep Behavior in Breast Cancer Survivors. Integr Cancer Ther. 2017 Mar;16(1):21-31. doi: 10.1177/1534735416651719. Epub 2016 Jun 1.
PubMed 27252076Bruno E, Gargano G, Villarini A, Traina A, Johansson H, Mano MP, Santucci De Magistris M, Simeoni M, Consolaro E, Mercandino A, Barbero M, Galasso R, Bassi MC, Zarcone M, Zagallo E, Venturelli E, Bellegotti M, Berrino F, Pasanisi P. Adherence to WCRF/AICR cancer prevention recommendations and metabolic syndrome in breast cancer patients. Int J Cancer. 2016 Jan 1;138(1):237-44. doi: 10.1002/ijc.29689. Epub 2015 Jul 28.
PubMed 26175188Berrino F, Villarini A, Traina A, Bonanni B, Panico S, Mano MP, Mercandino A, Galasso R, Barbero M, Simeoni M, Bassi MC, Consolaro E, Johansson H, Zarcone M, Bruno E, Gargano G, Venturelli E, Pasanisi P. Metabolic syndrome and breast cancer prognosis. Breast Cancer Res Treat. 2014 Aug;147(1):159-65. doi: 10.1007/s10549-014-3076-6. Epub 2014 Aug 8.
PubMed 25104441Villarini A, Pasanisi P, Traina A, Mano MP, Bonanni B, Panico S, Scipioni C, Galasso R, Paduos A, Simeoni M, Bellotti E, Barbero M, Macellari G, Venturelli E, Raimondi M, Bruno E, Gargano G, Fornaciari G, Morelli D, Seregni E, Krogh V, Berrino F. Lifestyle and breast cancer recurrences: the DIANA-5 trial. Tumori. 2012 Jan-Feb;98(1):1-18. doi: 10.1177/030089161209800101.
PubMed 22495696Djuric O, Bonvicini L, Pellegrini M, Bruno E, Pasanisi P, Gargano G, Curtosi P, Berrino F, Giorgi Rossi P, Villarini A. Diet, body composition and metabolic and hormonal profile in women at high risk of breast cancer recurrence: A secondary mediation analysis of the DIANA-5 trial. Clin Nutr. 2026 Jan;56:106537. doi: 10.1016/j.clnu.2025.11.021. Epub 2025 Dec 4.
PubMed 41483481De Santi M, Annibalini G, Marano G, Biganzoli G, Venturelli E, Pellegrini M, Lucertini F, Brandi G, Biganzoli E, Barbieri E, Villarini A. Association between metabolic syndrome, insulin resistance, and IGF-1 in breast cancer survivors of DIANA-5 study. J Cancer Res Clin Oncol. 2023 Sep;149(11):8639-8648. doi: 10.1007/s00432-023-04755-6. Epub 2023 Apr 27.
PubMed 37106164
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DIANA-5: Randomized Trial to Test the Efficacy of Dietary Change and Physical Activity to Prevent or Delay the Development of Recurrences in Breast Cancer Patients Estimated to be at High Risk of Recurrence Hormonal and Metabolic Reasons
- ClinicalTrials.gov ID
- NCT05019989
- Acronym / sponsor ID
- DIANA-5 / INT 37/07
- Conditions
- Breast Cancer Invasive
- Keywords
- Breast cancer, Diet, Physical activity, Recurrences
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,542 participants (actual)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Collaborators
- Associazione Italiana per la Ricerca sul Cancro, European Institute of Oncology, Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte, Federico II University, IRCCS Cancer Referral Center of Basilicata, ARNAS Civico Di Cristina Benfratelli Hospital, Lega Italiana per la Lotta contro i Tumori, Azienda Socio Sanitaria Territoriale di Mantova, Ministero della Salute, Italy
- Study start
- 1 Jun 2008 (actual)
- Primary completion
- 30 Sep 2012 (actual)
- Study completion
- 30 Sep 2017 (actual)
- First posted
- 25 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators recruited 1542 Breast Cancer (BC) patients and to randomize the participants in two groups: 773 have received standard recommendations for healthy lifestyle without, however, any active support; 700 have received a combination of individual and group contacts over the course of one year, including kitchen courses, gym and dance classes, common meals and reinforcing meetings, with emphasis on a comprehensive dietary change including low saturated fat and low refined carbohydrates, and high whole grain cereals and pulses consumption. Compliance have been monitored through weight change and plasma glucose, triglycerides, cholesterol and testosterone.
The main analysis will be by intention to treat. Under the hypothesis of reducing recurrence rate by 25% or 33% the statistical power of the study is 80% or, respectively, 90%, (P<0.05, 5-year follow-up).
Detailed description
Aims The investigators have been proposing a randomized intervention trial of diet and physical activity to reduce BC relapse (local, distant), and second ipsilateral or contralateral BC risk, in BC patients at high metabolic-endocrine of recurrence risk.
Secondary aims:
- to evaluate the effect of the combined dietary and physical activity change on the prevalence of Metabolic Syndrome
- to evaluate the effect of the combined dietary and physical activity change on the prevalence on risk biomarkers (BMI > 24.9 kg/m^2)
- to evaluate the effect of the combined dietary and physical activity change on the prevalence on risk biomarkers (testosterone >= 0.4 ng/ml)
- to evaluate the effect of the combined dietary and physical activity change on the prevalence on risk biomarkers (insulin > pmol/l)
- to evaluate the effect of the intervention on the development of other life-style related health conditions (other cancers, diabetes, hypertension, dyslipidemia, total mortality)
Recruitment:
Potential participants have been recruited at the time of diagnosis through follow-up clinics, patients' associations, or the media. Patients have been requested to sign an informed consent, including authorization for getting blood samples, for storing samples for future studies. The investigators collected demographic information, fasting measure body weight, height, waist circumference, and blood pressure, blood glucose, LDL and HDL cholesterol, triglycerides, testosterone and insulin. Eligible patients have filled in a baseline questionnaire on medical history, medication use, reproductive and body weight history, usual physical activity, and a validated semi-quantitative food frequency questionnaire.
Biological bank: the investigators collected and stored at -80°C one aliquot of whole blood, three 2-ml serum aliquot and two 2-ml buffy coat aliquot.
Randomization:
The investigators recruited 1542 patients' high risk and randomized the participants in two groups: 773 (control group) have received general standard written recommendation for healthy lifestyle without, however, any active support; 770 (intervention group) have received a combination of individual and group contacts over the course of one year, including kitchen courses, gym and dance classes, common meals and reinforcing meetings, with emphasis on a comprehensive dietary and life-style change.
Randomization has been carried out within strata of age, treatment (no adjuvant therapy, chemotherapy only, hormonal therapy only, both hormonal and chemotherapy) and axillary nodal status at diagnosis.
Patients who did not satisfy the high-risk criteria have been given the same general recommendations as the control group, and have been followed up as an external low risk group.
Intervention:
The intervention wanted aim to increase physical activity, controlling weight, and promoting healthy diet.
- Physical activity: achieve and maintain regular participation in a moderate intensity physical activity program of 210 minutes/week (30 min on average per day) over at least 3 days /week; decrease sedentary behaviors by 30 minutes/day on at least 5 days/week. During the first 12 months one group physical activity session per month offered to enhance program adoption. Women who wanted to take up vigorous sports encouraged to do so. For those who do not progressed to more vigorous activity, the focus was on maintaining moderate activities, such as walking. For self-monitoring and compliance enhancement, study participants had use logs, fill-in questionnaires and armband to monitor physical activity.
- Weight control: reducing energy intake relative to expenditure was the primary dietary focus for promoting weight loss in overweight or obese participants, while maintaining a healthy energy balance was the primary focus for normal weight participants. Participants were encouraged to include whole grains, pulses and high-fiber vegetables.
- Healthy diet: reducing calorie intake, through the preferred consumptions of highly satiating foods, such as unrefined cereals, legumes and vegetables, reducing high glycemic index food, high insulinemic foods, saturated fat, preferring instead unrefined vegetable fats, such as extra virgin olive oil, nuts and oleaginous seeds, reducing protein intake, mainly animal protein (except fish).
Baseline and yearly measurements:
Height and weight: electronic scale with women in light clothes and without shoes. In a sample of cases body fat and lean mass will be measured with bioelectric impedance (BIA).
Blood pressure: electronic device. Serum glucose, triglycerides and cholesterol: standard quality-controlled laboratory techniques.
Serum Testosterone and Insulin: Radioimmunoassay (RIA). For testosterone the investigators have used a direct RIA kit which has been validated by comparison with indirect assay after organic extraction of serum samples and celite purification.
Compliance:
Compliance has been monitored through lifestyle questionnaires, dietary questionnaires, weight change and plasma glucose, triglycerides, cholesterol, insulin, testosterone changes after one year of intervention. A compliance score has been computed, based on the direction of change in all these biomarkers.
Follow-up and outcome events:
The main outcome is the new BC events including:
- new primary breast cancer
- local/regional recurrence
- distant/metastatic recurrence The follow up have been based on the routine clinical follow-up at the collaborating hospitals, the periodic questionnaires to study participants, the regional cancer registry and hospital discharge diagnosis system, and death certificates.
Statistical power:
The survival of BC patients in Italy is dramatically increasing: 5-year relative survival increased from 80.6% for patients diagnosed in the early 1990s to 85.6% for patients diagnosed in the early 2000s. For these patients the estimated relapse free survival is 81.9. Such a survival improvement is accompanied by a postponement of the incidence of relapse.
The original aim was to recruit 1,200 high risk patients in order to have 600 patients per arm, which shall guarantee 80% chance of getting a significant difference also with 25% reduction, and allowing for 90% compliance in the intervention group and 10% contamination of the control group.
Statistical analysis:
Nowadays the investigators are assessing the baseline association between androgens, insulin, and several measures of adiposity including body mass index (BMI), waist circumference and percentage body fat, through Spearman correlation coefficients. Furthermore, the investigators are comparing the change in food consumption, body weight, and geometric means of hormones end points from baseline to 12 months in the intervention and control group.
The main analysis of the intervention effect on the incidence of recurrences is by intention to treat, i.e. based on assigned treatment at the time of randomization, regardless of adherence. Later, as a secondary analysis the investigators shall assess the effect by change in body weight and biomarkers. The investigators shall compute total survival and disease-free survival.
Hazard ratios and confidence intervals will be computed by the Cox proportional hazard model, with standard clinic-pathological prognostic covariates as potential confounders. Separate analyses will be carried out by Estrogen Receptors, Progesterone Receptors and erbB2 status. The investigators decided to carry out another follow-up in 2022 as the relapse time has lengthened to 10 years, due to new therapies, and to evaluate the effects on lifestyle due to closures during the pandemia severe acute respiratory syndrome-CoV-2.
Feasibility:
The principal investigator (at first dr. Franco Berrino and later dr. Anna Villarini) has long term experience in carrying on and coordinating epidemiological studies, including small-scale dietary intervention studies. The Milano National Cancer Institute and the others collaborating center is fully equipped with facilities for kitchen courses and gym facilities.
Control of potential biases:
Performance bias-patients have been recruited after the main treatments have been planned or delivered. In no case the allocation to the intervention or control group or the compliance will affect treatment.
Measurement bias-patients and researchers cannot be blinded, but the ascertainment of outcome was carried out by clinicians that were not involved in the study.
Attrition bias-Based on previous studies the investigators expect a fairly high compliance in the intervention group (>90%) but also some modification in the control group. After the main analysis by intention to treat, therefore, secondary analyses will be carried out by compliance score.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized Trial of Diet, Physical Activity and Breast Cancer Recurrences. The investigators recruited 1542 patients' high risk and randomized them in two groups: 773 (control group) have received general standard written recommendation for healthy lifestyle without, however, any active support; 769 (intervention group) have received a combination of individual and group contacts over the course of one year, including kitchen courses, gym and dance classes, common meals and reinforcing meetings, with emphasis on a comprehensive dietary and life-style change.
| Arm | Type | Receives |
|---|---|---|
| Intervention group: on diet and physical activity | Experimental | Behavioral: Intervention group on diet and physical activityIndividual advice on diet and on physical activity Kitchen courses to teach basic Mediterranean and macrobiotic recipes (two 1-day course plus ten 3-h courses associated with common dinner) (15-20 participants at a time) Fortnightly common lunch or dinner (50-60 participant at a time) Basic gymnastic course (twelve - monthly- 2-hour courses) * Study newsletter, with scientific information, kitchen recipes, study facilities * Periodic conferences on diet and health * Periodic reinforcement meetings with common meals, gymnastic sessions, and dancing, after the first year * Periodic body weight assessment (weekly self-measurement and monthly measurement at the study center) * Discounted rate for advanced kitchen courses * Psychological support groups |
| Control group: only public recommendations on lifestyle | Experimental | Behavioral: Control group: only public recommendation an lifestyle1. Invitation leaflet, explaining the rationale of the study and including basic life-style recommendations, based on the 1997 World Cancer Research Fund recommendations (to be updated in 2007) and the Italian National Institute of Nutrition food pyramid. 2. Dissemination of the information on the study by media 3. Yearly follow-up questionnaire on breast events and dietary and physical activity chang |
Who may qualify
- Ages
- 35 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Mastectomy or conservative surgery for invasive breast cancer, any type, in the last five years (the investigators recruited mostly patients at the time or after surgery, when chemotherapy has been concluded and hormonal therapy, if necessary, has been started)
- Absence of signs or symptoms suggestive of recurrences
- Presence of one or more of the following endocrine/metabolic indicators: serum testosterone level ≥ 0.4 ng/ml (1 nmol/ml), corresponding to the median value in BC patients, or serum insulin ≥ 50 pmol/L, corresponding to the upper quartile of insulin distribution in Breast Cancer patients, or metabolic syndrome, present in about 15% of Breast Cancer patients.
Key exclusion criteria (3 listed)
- Metastatic disease or previous relapse
- Age >70
- Physical or mental handicaps that would have impeded to engage in moderate physical activity or participate in kitchen classes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intervention group on diet and physical activityThe intervention wanted to increase physical activity, controlling weight, promoting healthy diet. 1. Physical activity: achieve and maintain regular participation in a moderate intensity physical activity program of 210 minutes/week (30 min on average per day) over at least 3 days /week; decrease sedentary behaviors by 30 minutes/day on at least 5 days/week 2. Weight control: reducing energy intake relative to expenditure is the primary dietary focus for promoting weight loss in overweight or obese participants, and maintaining a healthy energy balance is the primary focus for normal weight participants. Participants will be encouraged to include whole grains and high-fiber vegetables 3. Healthy diet: reducing calorie intake, through the preferred consumptions of unrefined cereals, pulses and vegetables, reducing high glycemic index food and high insulinemic foods, such as sugar and milk; reducing sources of saturated fat and animal protein (except fish) | Behavioural | Intervention group: on diet and physical activity |
| Control group: only public recommendation an lifestyle1. Invitation leaflet, explaining the rationale of the study and including basic life-style recommendations, based on the 1997 World Cancer Research Fund recommendations (to be updated in 2007) and the Italian National Institute of Nutrition food pyramid. 2. Dissemination of the information on the study by media 3. Yearly follow-up questionnaire on breast events and dietary and physical activity chang | Behavioural | Control group: only public recommendations on lifestyle |
Primary outcome
Reduction of recurrences
Time frame: Baseline, fifth year
The investigators have been proposing a randomized intervention trial of diet and physical activity to change BC relapse (local, distant), and second ipsilateral or contralateral BC, in BC patients at high risk of recurrence because of biochemical markers of increased risk, namely high serum testosterone and/or high fasting insulin and/or metabolic syndrome. Several other markers of increased recurrence risk are available, such as cancer stage at diagnosis, histological grade, hormonal receptors and other gene expression profile. All these will be registered, but the investigators are specifically interested in markers of the host that can be modified through life-style.
7 secondary outcomes
Modification lifestyle and Metabolic Syndrome (MetS)
Time frame: Baseline, first year
Modification lifestyle and Body Mass Index (BMI)
Time frame: Baseline, first year
Modification lifestyle and Testosterone
Time frame: Baseline, first year
Modification lifestyle and Insulin
Time frame: Baseline, first year
Development other cancer
Time frame: Baseline, fifth year
Development diabetes
Time frame: Baseline, fifth year
Total mortality
Time frame: Baseline, fifth year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Results publication: PubMed 31177874Roveda E, Bruno E, Galasso L, Mule A, Castelli L, Villarini A, Caumo A, Esposito F, Montaruli A, Pasanisi P. Rest-activity circadian rhythm in breast cancer survivors at 5 years after the primary diagnosis. Chronobiol Int. 2019 Aug;36(8):1156-1165. doi: 10.1080/07420528.2019.1621330. Epub 2019 Jun 10.
- Results publication: PubMed 27252076Roveda E, Vitale JA, Bruno E, Montaruli A, Pasanisi P, Villarini A, Gargano G, Galasso L, Berrino F, Caumo A, Carandente F. Protective Effect of Aerobic Physical Activity on Sleep Behavior in Breast Cancer Survivors. Integr Cancer Ther. 2017 Mar;16(1):21-31. doi: 10.1177/1534735416651719. Epub 2016 Jun 1.
- Results publication: PubMed 26175188Bruno E, Gargano G, Villarini A, Traina A, Johansson H, Mano MP, Santucci De Magistris M, Simeoni M, Consolaro E, Mercandino A, Barbero M, Galasso R, Bassi MC, Zarcone M, Zagallo E, Venturelli E, Bellegotti M, Berrino F, Pasanisi P. Adherence to WCRF/AICR cancer prevention recommendations and metabolic syndrome in breast cancer patients. Int J Cancer. 2016 Jan 1;138(1):237-44. doi: 10.1002/ijc.29689. Epub 2015 Jul 28.
- Results publication: PubMed 25104441Berrino F, Villarini A, Traina A, Bonanni B, Panico S, Mano MP, Mercandino A, Galasso R, Barbero M, Simeoni M, Bassi MC, Consolaro E, Johansson H, Zarcone M, Bruno E, Gargano G, Venturelli E, Pasanisi P. Metabolic syndrome and breast cancer prognosis. Breast Cancer Res Treat. 2014 Aug;147(1):159-65. doi: 10.1007/s10549-014-3076-6. Epub 2014 Aug 8.
- Results publication: PubMed 22495696Villarini A, Pasanisi P, Traina A, Mano MP, Bonanni B, Panico S, Scipioni C, Galasso R, Paduos A, Simeoni M, Bellotti E, Barbero M, Macellari G, Venturelli E, Raimondi M, Bruno E, Gargano G, Fornaciari G, Morelli D, Seregni E, Krogh V, Berrino F. Lifestyle and breast cancer recurrences: the DIANA-5 trial. Tumori. 2012 Jan-Feb;98(1):1-18. doi: 10.1177/030089161209800101.
- Derived from this study: PubMed 41483481Djuric O, Bonvicini L, Pellegrini M, Bruno E, Pasanisi P, Gargano G, Curtosi P, Berrino F, Giorgi Rossi P, Villarini A. Diet, body composition and metabolic and hormonal profile in women at high risk of breast cancer recurrence: A secondary mediation analysis of the DIANA-5 trial. Clin Nutr. 2026 Jan;56:106537. doi: 10.1016/j.clnu.2025.11.021. Epub 2025 Dec 4.
- Derived from this study: PubMed 37106164De Santi M, Annibalini G, Marano G, Biganzoli G, Venturelli E, Pellegrini M, Lucertini F, Brandi G, Biganzoli E, Barbieri E, Villarini A. Association between metabolic syndrome, insulin resistance, and IGF-1 in breast cancer survivors of DIANA-5 study. J Cancer Res Clin Oncol. 2023 Sep;149(11):8639-8648. doi: 10.1007/s00432-023-04755-6. Epub 2023 Apr 27.
- Individual participant dataSharing planned: Yes. The study protocol, dataset, statistical analysis plan, informed consent form and clinical study report were discussed through meetings held with all the collaborating centers. The individual participant data (IPD) were delivered to the coordinators of the individual centers in coded anonymous.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ANNA VILLARINI, PhD principal investigator
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Questions about this trial
What is this clinical trial studying?
A study testing Intervention group on diet and physical activity in people with Breast Cancer Invasive, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction of recurrences (time frame: Baseline, fifth year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05019989, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021; AzTrials last refreshed its copy on 8 Nov 2026.