Long-term Follow-up of the TAM-01 Study and Pooled Analysis of Low-dose Tamoxifen Studies in Non-invasive or Microinvasive Breast Neoplasms

NCT06982313 | Completed

• 2 other identifiers: Low-dose tamoxifen studies2007-007740-10
• Study Type: observational
• Target: 1,545
• Locations: 1 country
• Sites: 2

Brief Summary

Low-dose tamoxifen (5 mg/day for three years, BabyTam) has emerged as a safer and effective alternative to the standard regimen (20 mg/day), reducing breast cancer recurrence with fewer adverse events. The TAM-01 phase III trial demonstrated a 42% reduction in breast cancer events over ten years compared to placebo in women with ductal carcinoma in situ (DCIS) or high-risk lesions (HRL, ADH, LCIS), supporting its inclusion in clinical guidelines. The phase III TAM-01 trial enrolled 500 women, comparing low-dose tamoxifen to placebo over three years, with a median follow-up of 9.7 years (IQR, 8.3-10.9). Results showed a significant reduction in invasive breast cancer (HR = 0.58; 95% CI: 0.35-0.95; p = 0.03) and in contralateral breast cancer, CBC (HR = 0.36; 95% CI: 0.14-0.92; p = 0.025), with no increase in serious adverse events. Exploratory analyses suggested a greater benefit in postmenopausal women (HR = 0.30; 95% CI: 0.11-0.82), compared to premenopausal women (HR = 0.73; 95% CI: 0.30-1.76), though this interaction did not reach statistical significance (p-interaction = 0.13). However, our unpublished data indicate a remarkable reduction of CBC in premenopausal women on BabyTam. The TAM-01 long-term follow-up study aims to extend the follow-up of TAM-01 participants, evaluating long-term outcomes, including incidence of invasive breast cancer and DCIS, with a focus on tumor laterality and menopausal status, as well as to assess other non-invasive events (LCIS, ADH, or ALH) and adverse outcomes of special interest. We will also perform a pooled analysis of our three low-dose tamoxifen studies to increase the statistical power of our findings, with special attention to the effect according to menopausal status and site of recurrence. The primary endpoint will be the breast cancer-free interval. The findings are expected to strengthen the evidence supporting low-dose tamoxifen as a viable prevention strategy in high-risk populations with intraepithelial neoplasia (IEN or DCIS+HRLs) or microinvasive disease.

Conditions

Breast Cancer Invasive

Keywords

Low-Doses; Breast Cancer; Tamoxifen; Long-term follow up; DCIS; clinical trial, phase III; breast intraepithelial neoplasia; precancerous conditions; biomarkers; Insulin-Like Growth Factor Binding Proteins

Outcome Measures

Primary Outcomes (2)

• Incidence of invasive breast cancer and breast cancer-free interval

  The primary objective is to compare the incidence of invasive breast cancer and ductal carcinoma in situ in a long-term follow-up of the TAM-01 study and to compare the breast cancer-free interval among the three low-dose tamoxifen studies.

  Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.

• Incidence of invasive breast cancer and ductal carcinoma in situ (DCIS) considering tumor laterality and menopausal status

  To compare the incidence of invasive breast cancer and DCIS by tumor site (ipsilateral or contralateral) and menopausal status.

  Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.

Secondary Outcomes (4)

• Incidence of other non-invasive events

  Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.

• Overall Survival and Breast Cancer Survival (OS)

  Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.

• Adverse Events

  Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.

• Biomarkers evaluation

  Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.

Other Outcomes (1)

• Exploratory Endpoint: Correlation between biomarkers

  Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually

Study Arms (2)

Tamoxifen

All women received one tablet of tamoxifen 5 mg per day for 3 years during the TAM-01 phase III trial.

Drug: Tamoxifen (Nolvadex)

Placebo

All women received one tablet of placebo per day for 3 years during the TAM-01 phase III trial.

Drug: Tamoxifen (Nolvadex) placebo

Interventions

Tamoxifen (Nolvadex) DRUG

5 mg per day for 3 years during TAM-01 phase III trial

Tamoxifen

Tamoxifen (Nolvadex) placebo DRUG

Tamoxifen (Nolvadex) placebo per day for 3 years during TAM-01 phase III trial.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of all women previously enrolled in the TAM-01 study (EudraCT number: 2007-007740-10), and in the IEO-S007 trial and the prospective cohort study.

You may qualify if:

• Women with DCIS or high-risk lesions or pT1aN0 breast cancer previously enrolled in the TAM-01 trial (EudraCT number: 2007-007740-10) and in the IEO-S007 trial and the prospective cohort study.
• Written informed consent.

You may not qualify if:

• None.

Sponsors & Collaborators

• Ente Ospedaliero Ospedali Galliera: lead
• Fundacao Champalimaud: collaborator
• European Institute of Oncology: collaborator

Study Sites (2)

Unknown Facility

Genova, Italy, 16145, Italy

Location

E. O. Ospedali Galliera

Genoa, Italy

Location

Related Links

• TAM-01 study (EudraCT number: 2007-007740-10).
• TAM-01 study (ClinicalTrials.gov ID: NCT01357772).

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Precancerous Conditions

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Andrea De Censi, MD

  Champalimaud Foundation - Champalimaud Clinical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 21, 2025
• Study Start: July 1, 1996
• Primary Completion: March 1, 2026
• Study Completion: March 8, 2026
• Last Updated: March 11, 2026

Record last verified: 1996-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

IT (2)