NCT06033092

Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion

Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion: a Randomized Phase II Biomarker Trial in Subjects at Increased Risk

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Sponsor: European Institute of Oncology · Academic / Other
• Sex: Female
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Circulating levels of Sex Hormone Binding Globulin (SHBG) are significantly associated with a decreased risk of breast cancer. The main aim of this clinical trial is to verify whether Low Dose Tamoxifen (LDT) increases circulating levels of SHBG more than lifestyle intervention (LI) with or without intermittent caloric restriction (ICR) after 6 months in women at increased risk of breast cancer (i.e., healthy participants carriers of a germline pathogenic/likely pathogenetic variant in at least one of the following genes: BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51C or RAD51D, or with \> 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models or with a recently resected intraepithelial neoplasia of the breast (IEN). The secondary aims are: * to verify whether ICR significantly modulates primary and secondary endpoints such as Homeostasis Model Assessment (HOMA) index, immune and inflammatory markers, lipid profile, Adiponectin/Leptin (A/L) ratio, quality of life (QoL), Body mass index (BMI), fat body composition, safety and toxicity; * to verify whether LDT significantly modulates secondary endpoints, such as HOMA-index, immune and inflammatory markers, lipid profile, A/L ratio, QoL, BMI, fat body composition, safety and toxicity; * to investigate differences in microbiome composition by arms and the effect of changes in microbiome on QoL taking into account circulating biomarkers, cytokines, immune modulators, and inflammatory proteins in serum; * to investigate MD (Mammographic Breast Density) changes by LDT vs. LI, with or without ICR. This aim will be performed in a subgroup of participants (not all the participants will undergo mammography due to younger age).

Detailed description

Italian, multicenter, phase II, biomarker trial. A total of 200 women aged 18-70 years will be randomly assigned (1:1:1:1) to one of the four intervention arms Arm 1: Low dose Tamoxifen (LDT) i.e. 10 mg every other day; Arm 2: Low dose Tamoxifen (LDT) + Intermittent Caloric Restriction (ICR); Arm 3: Lifestyle intervention (LI) using a step counter; Arm 4: Lifestyle intervention (LI) using a step counter + Intermittent Caloric Restriction (ICR). Participants will be stratified by center and by disease status (high risk vs. previous IEN) and intervention will last six months for all arms.

Conditions

• BRCA Mutation
• PALB2 Gene Mutation
• Ductal Carcinoma in Situ
• Lobular Carcinoma in Situ
• ATM Gene Mutation
• CHEK2 Gene Mutation
• CDH1 Gene Mutation
• RAD51C Gene Mutation
• RAD51D Gene Mutation

Interventions

Type	Name	Description
DRUG	Tamoxifen 10 mg Tablet	One tablet of Tamoxifen 10 mg every other day for 6 months
OTHER	Intermittent caloric restriction	"5:2 diet": 5 days a week at regular energy intake and 2 days/week at 75% energy deficit (diet will be restricted at 500-800 kcal corresponding to a 75% reduction compared to normal size)
BEHAVIORAL	Step counter Device	Participants will receive personal advice on healthy lifestyle and a step counter

Timeline

• Start date: 2024-06-21
• Primary completion: 2025-12-01
• Completion: 2026-01-01
• First posted: 2023-09-13
• Last updated: 2025-08-28

Locations

4 sites across 1 country: Italy