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

This study is testing whether a low dose of Tamoxifen can raise certain hormone levels better than lifestyle changes in women at higher risk for breast cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: European Institute of Oncology (other)
• Locations: 4 sites (Genoa and 3 other locations)
• Trial ID: NCT06033092 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine if Low Dose Tamoxifen (LDT) can increase levels of Sex Hormone Binding Globulin (SHBG) more effectively than lifestyle interventions, including intermittent caloric restriction, in women at increased risk of breast cancer. The study will randomly assign 200 women aged 18-70 to one of four intervention arms over a six-month period. Participants will be monitored for changes in SHBG levels and other health markers, with a focus on those carrying specific genetic mutations or with a high risk of breast cancer. The trial is conducted across multiple centers in Italy.

Who should consider this trial

Good fit: Ideal candidates are women aged 18-70 who are carriers of specific genetic mutations or have a high risk of breast cancer.

Not a fit: Patients without a genetic predisposition to breast cancer or those with a low risk may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new preventive strategy for women at high risk of breast cancer.

How similar studies have performed: Other studies have shown promise in using lifestyle interventions and hormonal treatments for breast cancer prevention, but this specific combination is novel.

Eligibility criteria

Inclusion Criteria:

1. Women between 18 and 70 years old;
2. 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;
3. Ability to understand and the willingness to sign a written informed consent document;
4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1;

5a. For high-risk strata: A negative mammogram or any radiological image based on age and center protocol screening within 6 months before baseline visit;

5b. For IEN Strata: A negative mammogram within 12 months before baseline visit;

6. A negative transvaginal ultrasound within 6 months before baseline visit.

Exclusion Criteria:

1. Diagnosis of ER-negative (\<10%) DCIS, or history of invasive breast cancer;
2. Previous treatment with SERMs or any other hormonal treatment for breast neoplasms;
3. BMI \< 18.5 Kg/m2 and/or Malnutrition Universal Screening Tool (MUST) score ≥2 and/or any current or past eating disorders;
4. Any diagnosis of invasive neoplasia, except non-melanoma skin cancer, in the previous 5 years;
5. 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);
6. Current use of warfarin or other anticoagulant drugs
7. Bilateral mastectomy;
8. Pregnancy or desire to become pregnant in the subsequent 9 months after treatment cessation;
9. Diabetes or any other clinical condition that at the investigator's discretion contraindicates the proposed intervention.
10. No hormonal contraception is allowed during study intervention. Non-hormonal methods will be advised for women of childbearing potential (WOCBP)

Where this trial is running

Genoa and 3 other locations

• E.O. Galliera — Genoa, Italy (NOT_YET_RECRUITING)
• Istituto Europeo di Oncologia — Milan, Italy (NOT_YET_RECRUITING)
• Istituto Nazionale Tumori G. Pascale — Napoli, Italy (NOT_YET_RECRUITING)
• Istituto Oncologico Veneto — Padova, Italy (RECRUITING)

Study contacts

• Principal investigator: Bernardo Bonanni, MD — Istituto Europeo di Oncologia
• Study coordinator: Bernardo Bonanni, MD

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