Dietary Intervention and BRCA Penetrance

NCT03066856 | Completed DMC

• 1 other identifier: 106/13
• Study Type: interventional
• Target: 502
• Locations: 1 country
• Sites: 1

Brief Summary

Insulin-like growth factor I (IGF-I) and other markers of insulin resistance (IRm) might modulate the penetrance of BRCA genes mutation. The investigators have designed a demonstration project with BRCA mutation carriers (with or without a previous diagnosis of breast cancer) to test:

1. 1.whether a lifestyle intervention significantly reduceIGF-I and the other IRm (randomized trial).
2. 2.whether mutation carriers with a previous diagnosis of breast cancer have higher IRm than carriers without breast cancer (case-controlstudy).
3. 3.whether IRm and their change over time affect subsequent breast cancer incidence and prognosis (cohort follow-up).

Conditions

Dietary Modification; BRCA1 Mutation; BRCA2 Mutation; Breast Cancer

Keywords

BRCA genes; Mutation carriers; IGF-I; Diet

Outcome Measures

Primary Outcomes (2)

• Reduction of serum levels of IGF-I (ng/mL) (intervention trial).

  Final analyses will be performed by intention to treat. By assuming that: a) the planned lifestyle interventions may reduce IGF-I levels by 10%, b) alpha error = 0.05, the investigators shall have 96% power to compare 300 women included in the intervention group versus 300 in the control group.

  6 months of dietary intervention

• Case-control analysis: comparison of the affected versus the unaffected BRCA mutation carriers for the baseline IRm levels baseline serum levels of IGF-I and IRm.

  By classifying the exposure status according to the IGF-I median level and by assuming that : 1. the probability of exposure among controls is 50 %, 2. a case/control ratio of 2/1 (as in a pilot study): 400 women with a previous diagnosis of BC and 200 unaffected, 3. the true odds ratio for BC in exposed versus unexposed subjects ranging between 1.5 to 2 (the lower confidence interval of a pilot study), the investigators will be able to reject the null hypothesis ( that this odds ratio equals 1) with a power ranging from 64% to 97% at the alpha level of 0.05.

  3 years

Secondary Outcomes (1)

• Survival analysis: evaluation of the association between IGF-I and IGF-I changes and subsequent BC incidence and BC prognosis (BC incidence for unaffected women and ipsilateral or contralateral BC and BC recurrences for affected women).

  3 years

Study Arms (2)

Intervention

EXPERIMENTAL

After baseline examinations, participants are randomized to an active dietary intervention group.The intervention group is invited to attend six full days of life-style intervention activities over the next six months. These activities include six cookery courses followed by lunch, six physical activity sessions (walking for 45 minutes) and six conferences. The intervention and control groups both complete questionnaires on adherence to the Mediterranean diet (MEDAS) at baseline and at the end of the study, and are asked for at least two 24-hour recalls of the previous day's food intake, and details of their physical exercise during the six-month intervention.

Other: Dietary intervention

Control

NO INTERVENTION

All participants receive general recommendations for the dietary prevention of cancer. After baseline examinations, women randomized in the control group carry on following the baseline recommendations.

Interventions

Dietary intervention OTHER

The main aim of the trial is to reduce serum levels of IGF-I and IRm with a a low- calorie and low-protein diet. In humans, calorie restriction alone does not seem to significantly lower IGF-I; protein restriction is also required. In detail, recommendations for participants included in the intervention arm include: * reducing protein intake, mainly milk and animal protein (except fish), down to 10-12% of total calorie intake. * reducing high glycemic index food and high insulinemic foods. * reducing sources of saturated fat (red and processed meat, milk and dairy products). * eating mostly food of plant origin, with a wide variety of seasonal products.

Intervention

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible study subjects are women, aged 18-70, either unaffected or affected with BC, without metastases or previous ovarian cancer, who underwent genetic counselling and fulfilled high-risk selection criteria for genetic testing based on personal and/or family history and resulted carriers of deleterious BRCA mutations.

You may not qualify if:

• Unaffected BRCA mutation carriers with bilateral prophylactic mastectomy are not included in the cohort or are censored at the time of surgery.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• Istituto Oncologico di Bari: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Related Publications (1)

• Bruno E, Oliverio A, Paradiso A, Daniele A, Tommasi S, Terribile DA, Filippone A, Digennaro M, Pilato B, Danza K, Guarino D, Rossi C, Rossi MM, Venturelli E, Giussani M, Peissel B, Pasanisi P. Lifestyle Characteristics in Women Carriers of BRCA Mutations: Results From an Italian Trial Cohort. Clin Breast Cancer. 2021 Jun;21(3):e168-e176. doi: 10.1016/j.clbc.2020.11.002. Epub 2020 Nov 10.

  PMID: 33357965 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Diet Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nutrition Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: BRCA mutation carriers, with or without breast cancer, aged 18-70 years and without metastases are eligible. After the baseline examinations, women are randomized to an active dietary intervention or to a control group. The intervention group should attend six full days of activities over the next six months.

Study Record Dates

• First Submitted: February 20, 2017
• First Posted: March 1, 2017
• Study Start: December 1, 2015
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: October 4, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)