Tamoxifen for Breast Cancer Risk Reduction

Recruiting at 11 trial locations

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers, CYP2D6 inhibitors, Warfarin

Disqualifiers: Invasive breast cancer, Bilateral breast surgery, Thromboembolism, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a low dose of tamoxifen (also known as Nolvadex or Tamoxifen citrate) can reduce breast density, a known risk factor for breast cancer, in women at higher-than-average risk. Tamoxifen blocks estrogen's effects in the breast, and even at reduced doses, it has shown promise in lowering breast density. The trial is designed for premenopausal women with a history of certain breast conditions or those identified as having a higher risk of breast cancer through specific assessments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in breast cancer prevention.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically strong CYP3A4 inducers or strong CYP2D6 inhibitors, unless you can switch to an alternative medication with your doctor's guidance. If you are currently taking Warfarin, you will not be eligible to participate.

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

Research has shown that tamoxifen is generally safe for use and has long been used to lower the risk of breast cancer. Studies have found that tamoxifen can reduce the chance of developing invasive breast cancer by 43%, demonstrating its effectiveness and safe use by many women.

Tamoxifen is often prescribed in a lower dose to reduce breast density, which is also considered safe. Common side effects include hot flashes and an increased risk of blood clots, though serious issues are rare. The low-dose version aims to lower these risks while still helping to reduce breast density, which is linked to breast cancer risk.

In summary, tamoxifen has a strong safety record, and its benefits usually outweigh the risks, especially for those at higher risk of breast cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer risk reduction, which often involve higher doses or different medications, this trial focuses on using tamoxifen at lower doses. The unique approach here is the tailored dosing based on mammogram results, allowing for adjustments in the tamoxifen dose to optimize effectiveness while potentially reducing side effects. Researchers are excited about this because it could offer a more personalized treatment option that balances efficacy with a better side effect profile, making it more appealing for preventive use.

What is the effectiveness track record for tamoxifen in reducing breast cancer risk?

Research has shown that tamoxifen, which participants in this trial will receive, can lower the risk of breast cancer, particularly in women with dense breast tissue. Tamoxifen blocks estrogen in the breast, reducing the chance of developing breast cancer. Studies have found that tamoxifen can cut the risk of invasive breast cancer by 49%. Even at low doses, tamoxifen decreases breast cancer cases. Its approval for preventing breast cancer proves its effectiveness in reducing risk. ^{4 5 6 7 8}

Who Is on the Research Team?

Seema A. Khan, M.D.

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for premenopausal women at higher than average risk for breast cancer, particularly those with dense breasts. The study aims to find the best dose of Tamoxifen that can reduce breast density and thus lower the risk of developing breast cancer.

Inclusion Criteria

I am a woman taking medication to control my HSV infection.

Women of child-bearing potential agreeing to use adequate contraception

Ability to understand and sign a written informed consent document

Exclusion Criteria

Receiving any other investigational agents

Uncontrolled intercurrent illness or psychiatric illness/social situations limiting compliance

I have used SERMs for more than a year in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive tamoxifen 5mg PO QD for 6 months. Dose escalation based on response.

6 months

Monthly visits (in-person)

Dose Escalation

Participants with less than 10% reduction in dense area escalate to 10mg or 20mg tamoxifen.

6-12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tamoxifen

Trial Overview The RENAISSANCE Trial is testing low-dose Tamoxifen's effectiveness in reducing breast density among high-risk women. It includes assessments like questionnaires, biopsies, biospecimen collection, and mammography to monitor changes and responses.

How Is the Trial Designed?

Group I: Prevention (tamoxifen) Experimental Treatment 5 Interventions

Participants receive tamoxifen 5mg PO QD for 6 months. Participants with aDAR \>= 10% on mammogram at 6 months continue receiving tamoxifen 5mg PO QD for 12 months. Participants with aDAR \< 10% at 6 months are escalated to receive tamoxifen 10mg PO QD for 6 months. Participants with aDAR \>= 10% after 6 months of tamoxifen 10mg continue receiving tamoxifen 10 mg PO QD for 6 months. Participants with aDAR \< 10% after 6 months of tamoxifen 10mg are given the option of continuing tamoxifen 10mg or escalating to receive tamoxifen 20mg PO QD for 6 months. Participants undergo mammography and collection of blood samples at screening and on study. Participants may optionally undergo biopsy at screening and on study.

Tamoxifen is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Nolvadex for:

• Breast cancer
• Infertility
• Gynecomastia

Approved in United States as Tamoxifen citrate for:

• Breast cancer
• Reduction in breast cancer incidence in high-risk women
• McCune-Albright Syndrome

Approved in Canada as Tamoxifen for:

• Breast cancer
• Reduction in breast cancer incidence in high-risk women

Approved in Japan as Tamoxifen for:

• Breast cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Tamoxifen is being evaluated in ongoing clinical trials involving over 24,000 healthy women to determine its effectiveness in preventing breast cancer, with results expected by the year 2000.

While tamoxifen may provide significant benefits in breast cancer prevention, it is associated with adverse effects such as transient bone loss in premenopausal women and potential uterine complications in postmenopausal women, leading to investigations of alternative drugs like raloxifene and toremifene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of antiestrogen breast cancer prevention trials. Powles, TJ.[2016]

In a study of 114 women with rheumatoid arthritis treated with leflunomide for 12 months, there was no significant association found between the CAG repeat polymorphism in the androgen receptor gene and the effectiveness of the treatment.

The results indicate that genetic variations in the androgen receptor do not influence the response to leflunomide in improving disease activity in women with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of association between CAG repeat polymorphism in the androgen receptor gene and the outcome of rheumatoid arthritis treatment with leflunomide. Dziedziejko, V., Kurzawski, M., Safranow, K., et al.[2021]

Leflunomide (LEF), a drug typically used for rheumatoid arthritis, showed promising antitumor effects in oral squamous cell carcinoma (OSCC) by inhibiting cell proliferation and blocking the cell cycle at the S phase.

LEF not only reduced tumor growth in a xenograft model but also affected key cellular processes by upregulating cyclin A and downregulating dihydroorotate dehydrogenase, suggesting its potential as a new treatment option for OSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leflunomide inhibits proliferation and tumorigenesis of oral squamous cell carcinoma. Ren, A., Fu, G., Qiu, Y., et al.[2018]

Tamoxifen has been proven effective in improving recurrence-free and overall survival rates in breast cancer patients, making it the preferred long-term treatment for selected individuals.

While tamoxifen carries a small risk of developing endometrial cancer (approximately 2 per 1,000 women annually), most cases are detected early and are highly treatable, suggesting that the benefits of tamoxifen generally outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of tamoxifen on the endometrium. Barakat, RR.[2013]

In a study of 3,325 veterans, leflunomide (LEF) was found to be relatively safe, with the most common reasons for discontinuation being inefficacy and gastrointestinal symptoms.

The data indicated that younger patients, older patients, and those with lower income were more likely to discontinue LEF, suggesting that these factors may influence treatment adherence and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leflunomide use during the first 33 months after food and drug administration approval: experience with a national cohort of 3,325 patients. Siva, C., Eisen, SA., Shepherd, R., et al.[2018]

In a study of 105 patients with rheumatoid arthritis, 34 discontinued leflunomide due to toxicity, highlighting a significant issue with treatment adherence.

Carriers of the C allele of the CYP1A2 gene were found to have a 2.29 times higher risk of stopping leflunomide due to side effects, suggesting a genetic factor that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic polymorphism of CYP1A2 but not total or free teriflunomide concentrations is associated with leflunomide cessation in rheumatoid arthritis. Hopkins, AM., Wiese, MD., Proudman, SM., et al.[2021]

In a study of 50 postmenopausal women with metastatic breast cancer who had not responded to previous treatments, tamoxifen citrate led to a complete remission in 8% and a partial remission in 28% of patients, with a median response duration of eight months.

Tamoxifen was found to significantly prolong survival in responders compared to nonresponders, and the side effects of the treatment were mild, making it a favorable option for patients after other therapies have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. Legha, SS., Buzdar, AU., Hortobagyi, GN., et al.[2019]

Tamoxifen can reduce the risk of developing invasive breast cancer by at least 49% in women at increased risk, particularly benefiting those with a 5-year risk of 1.67% or greater, lobular carcinoma-in-situ, or atypical hyperplasia.

While postmenopausal women also benefit from tamoxifen in reducing breast cancer risk and bone fractures, they must consider the potential risks of invasive endometrial cancer and thromboembolic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing the risk of breast cancer with tamoxifen in women at increased risk. Vogel, VG.[2013]

Tamoxifen citrate has been a crucial treatment for breast cancer over the past 25 years, significantly improving survival rates and reducing the risk of developing cancer in the other breast.

Patients appreciate the additional benefits of tamoxifen on cholesterol levels and bone health, but they also express concerns about potential side effects affecting their daily lives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen's impact on the management of breast cancer: patient perspectives. Reichman, BS.[2013]

Only 27.4% of surveyed primary care physicians prescribed tamoxifen for breast cancer prevention in the past year, indicating that its use is not widespread among these doctors.

Factors influencing the decision to prescribe tamoxifen included personal connections to breast cancer, patient inquiries about the drug, and the belief that its benefits outweigh the risks, while concerns about endometrial cancer risk had less impact on prescribing decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription of tamoxifen for breast cancer prevention by primary care physicians. Armstrong, K., Quistberg, DA., Micco, E., et al.[2015]

In a study of 105 rheumatoid arthritis patients, those with the CYP1A2*1F CC genotype had a significantly higher risk (9.7 times) of experiencing toxicity from leflunomide compared to those with the A allele, indicating a genetic factor influencing drug safety.

No significant associations were found between the CYP2C19 and CYP2C9 genotypes and leflunomide toxicity, suggesting that CYP1A2 is the primary genetic determinant affecting the drug's adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic polymorphism of CYP1A2 and the toxicity of leflunomide treatment in rheumatoid arthritis patients. Bohanec Grabar, P., Rozman, B., Tomsic, M., et al.[2021]

Citations

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Tamoxifen - StatPearls - NCBI Bookshelf - NIH This drug is particularly effective for patients with estrogen receptor–positive tumors and is approved by the US Food and Drug Administration ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01196936

Low-Dose Tamoxifen Citrate in Reducing Breast Cancer ... Study Overview. This phase IIb trial studies how well low-dose tamoxifen citrate works in reducing breast cancer risk in radiation-induced cancer survivors. ...

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

Tamoxifen for Prevention of Breast Cancer: Report of the ... Results: Tamoxifen reduced the risk of invasive breast cancer by 49 ... Also self-reported at each visit were data from the Medical Outcomes Study ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4053098/

Oral low dose and topical tamoxifen for breast cancer prevention A trend toward a beneficial effect from low dose tamoxifen in reducing breast cancer events was observed, with greater efficacy being seen in the ER+, PgR+, Ki- ...

5. thelancet.com thelancet.com/journals/lanonc/article/PIIS0140-6736(12)61963-1/fulltext

Long-term effects of continuing adjuvant tamoxifen to 10 ... The risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls (absolute recurrence reduction 3·7%); figure 3.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2005/17970s053lbl.pdf

NOLVADEX - (Tamoxifen Citrate) - accessdata.fda.gov For the primary endpoint, the incidence of invasive breast cancer was reduced by 43% among women assigned to NOLVADEX (44 cases - NOLVADEX, 74 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC117858/

Tamoxifen for breast cancer prevention: safety warning Tamoxifen is not appropriate for breast cancer prevention in women at low risk of the disease (5-year risk less than 1.66%), and discussions about modifiable ...

8. oncologynewscentral.com oncologynewscentral.com/drugs/monograph/4497-382414/tamoxifen-oral

Tamoxifen citrate: uses, dosing, warnings, adverse events, ... The updated analysis showed a 24% reduction in raloxifene efficacy in lowering the risk of invasive breast cancer compared with tamoxifen. Although raloxifene ...