Tamoxifen for Breast Cancer Risk after Radiation Therapy

(LDTam Trial)

Not currently recruiting at 12 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Hormone therapy, Anticoagulants

Disqualifiers: Thromboembolism, Pregnancy, High creatinine, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if low-dose tamoxifen citrate can reduce breast cancer risk in individuals who have undergone radiation therapy to the chest area. Tamoxifen blocks estrogen, a hormone that can promote breast cancer growth. The trial compares tamoxifen to a placebo, a substance with no active treatment, over 24 months. It seeks participants who received radiation therapy for conditions like lymphoma or leukemia before age 40 and have had no active disease for at least two years. Participants should have completed their primary cancer treatment at least six months before joining the trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as hormone replacement therapy, hormonal contraceptives, and some other hormone-related drugs, at least 6 months before joining. If you are taking warfarin or strong CYP2D6 inhibitors, you will not be allowed to participate.

Is there any evidence suggesting that tamoxifen citrate is likely to be safe for humans?

Research has shown that tamoxifen citrate is generally safe for use. Studies have found that a low dose of tamoxifen can lower the risk of breast cancer, particularly for those at high risk. Tamoxifen has been used for many years to help prevent breast cancer recurrence, and its safety is well-established.

Previous research indicated that most side effects were mild, such as hot flashes and fatigue. Serious side effects, like blood clots or an increased risk of uterine cancer, are rare but possible. However, the benefits of using tamoxifen to prevent breast cancer typically outweigh these risks.

Since this trial uses a low dose, the chance of serious side effects may be even lower. The FDA has approved tamoxifen for treating and preventing breast cancer, supporting its safety for this purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about tamoxifen citrate for reducing breast cancer risk after radiation therapy because it works by blocking estrogen receptors on breast cancer cells, which prevents the cancer from receiving signals to grow. Unlike chemotherapy, which attacks rapidly dividing cells indiscriminately, tamoxifen specifically targets hormone-driven cancer growth, potentially leading to fewer side effects. This hormonal therapy approach makes it a promising option for individuals who have undergone radiation therapy and are at risk for hormone receptor-positive breast cancer.

What evidence suggests that tamoxifen citrate might be an effective treatment for reducing breast cancer risk after radiation therapy?

Research has shown that tamoxifen citrate can lower the risk of breast cancer. One study found that women taking a low dose of tamoxifen had about a 52% lower chance of developing invasive breast cancer or ductal carcinoma in situ (DCIS), a non-invasive type. Another study showed that tamoxifen reduced the rate of non-invasive breast cancer from 2.68 per 1000 women in the placebo group to 1.35 in the tamoxifen group. Additionally, tamoxifen decreased the risk of invasive breast cancer by 40% and reduced breast cancer deaths by 57%. In this trial, participants will receive either tamoxifen citrate or a placebo to assess its effectiveness in reducing breast cancer risk, especially for those who have undergone radiation therapy. ^{6 7 8 9 10}

Who Is on the Research Team?

Smita Bhatia, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for radiation-induced cancer survivors who are at risk of breast cancer, have had chest radiation therapy by age 40, and have been disease-free for 2 years. Postmenopausal women or premenopausal women under 45 with regular periods can join. Exclusions include those with certain other cancers, recent hormone treatments, pregnancy plans within two years, or a history of blood clots.

Inclusion Criteria

I received radiation therapy in the chest area or total body irradiation of 12 Gy or more by age 40.

You have not had a period for 12 months, had surgery to remove both ovaries, or have a specific hormone level indicating you are postmenopausal.

My menopausal status is clearly defined.

Exclusion Criteria

I have signs of breast cancer on imaging but may continue if it's benign.

I have used hormone therapy or certain vaginal estrogen products recently.

Your SGOT or SGPT levels are more than double the normal range at the medical center.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tamoxifen citrate or placebo orally once daily for 24 months

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Tamoxifen Citrate

Trial Overview The study tests if low-dose tamoxifen citrate can reduce the risk of developing breast cancer in individuals previously treated with chest radiation. It involves comparing tamoxifen to a placebo and includes various assessments like mammography and questionnaires about quality of life.

How Is the Trial Designed?

Group I: Arm I (tamoxifen citrate) Experimental Treatment 10 Interventions

Patients receive tamoxifen citrate PO QD for 24 months in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (placebo) Placebo Group 10 Interventions

Patients receive placebo PO QD for 24 months in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

City of Hope National Medical Center

Collaborator

Trials

17

Recruited

8,900+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

St. Jude Children's Research Hospital

Collaborator

Trials

451

Recruited

5,326,000+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7887034/

A Randomized Phase IIb Study of Low-dose Tamoxifen in ... In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526820924003707

Low Dose Tamoxifen for Breast Cancer Prevention At a median follow up of 5 years, women taking low dose tamoxifen had an approximately 52% reduction in risk of invasive breast cancer or DCIS over placebo.

3. academic.oup.com academic.oup.com/jnci/article/90/18/1371/897928

Tamoxifen for Prevention of Breast Cancer: Report of the ... The average annual rate of noninvasive breast cancer per 1000 women was 2.68 in the placebo group compared with 1.35 in the tamoxifen group, yielding an RR of ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01342

Reassessing the Benefits and Harms of Risk-Reducing ... Risk-reducing tamoxifen with annual screening (± MRI) decreased the risk of invasive breast cancer by 40% and breast cancer death by 57%, compared with no ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00002644

Tamoxifen for the Prevention of Breast Cancer in High-Risk ... The results of the study showed that tamoxifen reduced the incidence of breast cancer by one third in these high risk women but with some serious side effects.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01196936

Low-Dose Tamoxifen Citrate in Reducing Breast Cancer ... To determine the impact of a two-year course of low-dose tamoxifen (tamoxifen citrate) administered at 5 mg per day on surrogate endpoint biomarkers of breast ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK532905/

Tamoxifen - StatPearls - NCBI Bookshelf - NIH For patients at high risk for breast cancer or DCIS who are taking tamoxifen for breast cancer risk reduction, it should be avoided if there is ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33272980/

A Randomized Phase IIb Study of Low-dose Tamoxifen in ... Purpose: Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors-a population with breast ...

9. cancer.gov cancer.gov/types/breast/research/10-years-tamoxifen

Ten Years of Tamoxifen Reduces Breast ... Taking adjuvant tamoxifen (Nolvadex®) for 10 years after primary treatment leads to a greater reduction in breast cancer recurrences and deaths than taking the ...

10. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-025-02059-w

Medications to reduce breast cancer risk: a network meta ... The NMA showed that tamoxifen and AIs reduce the risk of breast cancer in women at above-average risk and suggested that AIs could be more ...