NCT06033092

Brief 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).

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
200

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jun 2024

Geographic Reach
1 country

4 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 23, 2023

Completed
21 days until next milestone

First Posted

Study publicly available on registry

September 13, 2023

Completed
9 months until next milestone

Study Start

First participant enrolled

June 21, 2024

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2025

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2026

Completed
Last Updated

August 28, 2025

Status Verified

August 1, 2025

Enrollment Period

1.4 years

First QC Date

August 23, 2023

Last Update Submit

August 22, 2025

Conditions

BRCA MutationPALB2 Gene MutationDuctal Carcinoma in SituLobular Carcinoma in SituATM Gene MutationCHEK2 Gene MutationCDH1 Gene MutationRAD51C Gene MutationRAD51D Gene Mutation

Keywords

Low Dose TamoxifenIntermittent Caloric RestrictionSex Hormone Binding GlobulinLifestyle

Outcome Measures

Primary Outcomes (1)

  • Post intervention levels of circulating binding globulin

    Sex hormone binding globulin level after 6 months of intervention

    Through study completion, an average of 6 months

Study Arms (4)

Low dose tamoxifen

ACTIVE COMPARATOR

Tamoxifen 10 mg (1 tablet) every other day for 6 months.

Drug: Tamoxifen 10 mg Tablet

Low dose tamoxifen + Intermittent Caloric Restriction

ACTIVE COMPARATOR

Tamoxifen 10 mg (1 tablet) every other day for 6 months + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)

Drug: Tamoxifen 10 mg TabletOther: Intermittent caloric restriction

Lifestyle intervention

PLACEBO COMPARATOR

Step counter device

Behavioral: Step counter Device

Lifestyle Intervention + Intermittent Caloric Restriction

ACTIVE COMPARATOR

Step counter device + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)

Other: Intermittent caloric restrictionBehavioral: Step counter Device

Interventions

Tamoxifen 10 mg TabletDRUG

One tablet of Tamoxifen 10 mg every other day for 6 months

Also known as: Low dose tamoxifen
Low dose tamoxifenLow dose tamoxifen + Intermittent Caloric Restriction
Intermittent caloric restrictionOTHER

"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)

Lifestyle Intervention + Intermittent Caloric RestrictionLow dose tamoxifen + Intermittent Caloric Restriction
Step counter DeviceBEHAVIORAL

Participants will receive personal advice on healthy lifestyle and a step counter

Lifestyle Intervention + Intermittent Caloric RestrictionLifestyle intervention

Eligibility Criteria

Age18 Years - 70 Years
Sexfemale(Gender-based eligibility)
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Women between 18 and 70 years old;
  • 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
  • \> 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models, or
  • with previous diagnosis of intraepithelial neoplasia (surgery for ADH, LCIS, ER positive DCIS) within the last 3 years;
  • Ability to understand and the willingness to sign a written informed consent document;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1;
  • a. For high-risk strata: A negative mammogram or any radiological image based on age and center protocol screening within 6 months before baseline visit;
  • b. For IEN Strata: A negative mammogram within 12 months before baseline visit;
  • \. A negative transvaginal ultrasound within 6 months before baseline visit.

You may not qualify if:

  • Diagnosis of ER-negative (\<10%) DCIS, or history of invasive breast cancer;
  • Previous treatment with SERMs or any other hormonal treatment for breast neoplasms;
  • BMI \< 18.5 Kg/m2 and/or Malnutrition Universal Screening Tool (MUST) score ≥2 and/or any current or past eating disorders;
  • Any diagnosis of invasive neoplasia, except non-melanoma skin cancer, in the previous 5 years;
  • Any tamoxifen contraindications (abnormal liver function, previous ischemic heart disease, endometrial disorder, previous deep venous thrombosis, history of pulmonary embolus, current or suspected glaucoma, retinopathy and cataract);
  • Current use of warfarin or other anticoagulant drugs
  • Bilateral mastectomy;
  • Pregnancy or desire to become pregnant in the subsequent 9 months after treatment cessation;
  • Diabetes or any other clinical condition that at the investigator's discretion contraindicates the proposed intervention.
  • No hormonal contraception is allowed during study intervention. Non-hormonal methods will be advised for women of childbearing potential (WOCBP)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

E.O. Galliera

Genoa, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Istituto Nazionale Tumori G. Pascale

Napoli, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

Related Publications (1)

  • Guerrieri-Gonzaga A, Serrano D, Gnagnarella P, Johansson H, Zovato S, Nardi M, Pensabene M, Buccolo S, DeCensi A, Briata IM, Pistelli L, Sansone C, Mannucci S, Aristarco V, Macis D, Lazzeroni M, Aurilio G, Accornero CA, Gandini S, Bonanni B. Low dose TamOxifen and LifestylE changes for bReast cANcer prevention (TOLERANT study): Study protocol of a randomized phase II biomarker trial in women at increased risk for breast cancer. PLoS One. 2024 Sep 3;19(9):e0309511. doi: 10.1371/journal.pone.0309511. eCollection 2024.

    PMID: 39226292DERIVED

MeSH Terms

Conditions

Carcinoma, Intraductal, NoninfiltratingBreast Carcinoma In Situ

Interventions

TamoxifenTablets

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsCarcinoma in SituNeoplasms, Ductal, Lobular, and MedullaryBreast NeoplasmsNeoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

StilbenesBenzylidene CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDosage FormsPharmaceutical Preparations

Study Officials

  • Bernardo Bonanni, MD

    Istituto Europeo di Oncologia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 23, 2023

First Posted

September 13, 2023

Study Start

June 21, 2024

Primary Completion

December 1, 2025

Study Completion

January 1, 2026

Last Updated

August 28, 2025

Record last verified: 2025-08

Locations

IT(4)