Tamoxifen vs. TamGel for Breast Cancer Risk Reduction

Not currently recruiting at 2 trial locations

Overseen By Jess Fischer

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Amy C. Degnim

Must not be taking: Anticoagulants, CYP2D6 inhibitors

Disqualifiers: Breast cancer, Thromboembolic disease, Pregnancy, 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: Unknown

Duration: Short-term

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two forms of tamoxifen, a medication used to reduce breast cancer risk, to assess their effects on breast tissue. Participants will receive either oral tamoxifen, a topical gel version, or a placebo. The goal is to determine which method is more effective and better tolerated. Women diagnosed with certain breast conditions, such as atypical hyperplasia, or those at increased risk of breast cancer may be suitable for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial requires you to stop taking certain medications. You cannot use potent inhibitors of tamoxifen metabolism like bupropion, fluoxetine, or paroxetine. You also need to avoid moderate or strong CYP2D6 inhibitors or CYP3A inducers. If you're on anticoagulation medications, you must stop those as well. Additionally, you cannot have used exogenous sex steroids, including oral contraceptives, within 1 month prior to the trial. Please consult with the study team for specific guidance on your medications.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, especially those that are moderate or strong inhibitors of tamoxifen metabolism, like bupropion and fluoxetine, and any anticoagulation medications. You should also avoid starting any new medications that might interact with tamoxifen during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that taking tamoxifen as a pill is generally safe for many people, though it can have side effects. It can lower the risk of breast cancer by about 50%. However, it is not recommended for women with a low risk of breast cancer. For most women, the benefits of tamoxifen outweigh the risks, but about 20% of users might experience more serious side effects, such as hot flashes, blood clots, and a higher risk of uterine cancer.

Early research suggests that the 4-hydroxytamoxifen (4-OHT) gel is well-tolerated when applied to the skin. It works similarly to the pill in slowing cell growth in breast tissue. The gel aims to reduce breast cancer risk with potentially fewer side effects than the pill. Some studies have shown that it may cause fewer unwanted effects because it targets the breast area directly, possibly reducing its impact on the rest of the body compared to the oral form. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore new ways to deliver tamoxifen, a drug commonly used to reduce the risk of breast cancer. Traditionally, tamoxifen is taken orally, but one of the new approaches involves a topical gel, called TamGel, which is applied directly to the breasts. This gel contains 4-hydroxytamoxifen, a form of tamoxifen, and offers a unique delivery method that might reduce systemic side effects associated with oral tamoxifen. By potentially minimizing side effects while still providing the protective benefits against breast cancer, these treatments could offer a more comfortable and effective option for patients.

What evidence suggests that this trial's treatments could be effective for breast cancer risk reduction?

Research has shown that tamoxifen pills can significantly lower the risk of breast cancer, particularly for those with tumors responsive to estrogen. Studies have found that tamoxifen can reduce the risk of invasive breast cancer by up to 49%. In this trial, participants will receive either oral Tamoxifen or a topical gel called 4-OHT, applied to the skin. Early research on 4-OHT indicates it reaches similar levels in breast tissue as the pills, suggesting the gel might offer similar protection. Both treatments have been well-tolerated in past studies, making them promising options for reducing breast cancer risk. ^{5 6 7 8 9}

Who Is on the Research Team?

Amy Degnim, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for women with a specific breast condition called atypical hyperplasia or LCIS, who can return for follow-up and handle questionnaires. They must have an ECOG status ≤1 (which means they're fully active or restricted in physically strenuous activity but ambulatory), use effective birth control, avoid sun exposure on breasts, and have good organ function. Pregnant women, recent thromboembolism patients, those treated for breast cancer within 2 years, or users of certain drugs are excluded.

Inclusion Criteria

I agree to use effective birth control during and for 2 months after the study, and I am not pregnant.

I am willing to keep my breast skin away from sunlight and tanning beds during the study.

If you can have children, you need to have a negative urine pregnancy test. If you cannot have children, your FSH levels need to show that you are in menopause.

Exclusion Criteria

I quit smoking more than 6 weeks ago.

I haven't used any hormonal treatments, including birth control pills, in the last month.

You had a blood clot in the past 5 years, you are currently pregnant or breastfeeding, or you had certain treatments for breast cancer in the past 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low-dose oral tamoxifen or topical 4-OHT gel for a short course to evaluate changes in breast tissue

Short-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

What Are the Treatments Tested in This Trial?

Interventions

• Tamoxifen

Trial Overview The study compares the effects of oral Tamoxifen versus a topical gel form (TamGel) against a placebo in altering breast tissue over a short period. Women will be randomly assigned to one of these treatments to see how each affects their condition.

How Is the Trial Designed?

Group I: Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day Experimental Treatment 2 Interventions

Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day +oral placebo

Group II: Oral Tamoxifen 10 mg/day Experimental Treatment 2 Interventions

Oral Tamoxifen 10 mg/day

Group III: Control Experimental Treatment 2 Interventions

Oral and gel placebo

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?

Amy C. Degnim

Lead Sponsor

Trials

1

Recruited

70+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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 has been shown to significantly reduce the risk of invasive breast cancer by 49% in high-risk women, according to the National Surgical Adjuvant Breast and Bowel Project P-1 trial, although some smaller European trials did not find a similar effect.

Due to potential side effects like endometrial cancer and thromboembolism, other agents such as raloxifene, which reduced breast cancer risk by 76% in a separate trial, are being investigated alongside tamoxifen for breast cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on breast cancer prevention. Rastogi, P., Vogel, VG.[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]

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 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 significantly reduces the incidence of estrogen receptor-positive (ER+) breast cancer in women identified as high-risk based on specific hormonal and reproductive characteristics, with a notable difference in breast cancer cases (3 in the tamoxifen group vs. 15 in the placebo group).

In contrast, tamoxifen did not show a significant effect in low-risk women, suggesting that its preventive benefits are primarily for those with higher risk factors, which could lead to more targeted and effective use of the drug in breast cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women. Veronesi, U., Maisonneuve, P., Rotmensz, N., et al.[2019]

In a study of 6048 women aged 40-70, 18% were identified as having a 5-year risk of invasive breast carcinoma greater than 1.66%, indicating a significant portion of the population may benefit from tamoxifen counseling for chemoprevention.

The number of women needed to screen to find one who would benefit from tamoxifen varied by age, ranging from 26 for those aged 40-49 to 142 for those aged 60-70, highlighting the importance of considering individual risk factors when recommending treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast carcinoma chemoprevention in the community setting. Estimating risks and benefits. Brewster, AM., Christo, DK., Lai, H., et al.[2015]

Citations

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

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. 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 ...

7. 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 ...

8. bccancer.bc.ca bccancer.bc.ca/drug-database-site/Drug%20Index/Tamoxifen_monograph.pdf

DRUG NAME: Tamoxifen The potential risks and benefits should be discussed, the lowest dose to relieve symptoms should be used, and treatment should be assessed ...

9. my.clevelandclinic.org my.clevelandclinic.org/health/treatments/9785-tamoxifen

Tamoxifen: Uses, Side Effects & Risks The study found that the benefits of tamoxifen outweighed the risks for 74% of their participants, but not for 20% of their participants.