Tamoxifen vs. TamGel for Breast Cancer Risk Reduction

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

65 Participants Needed

Trial Summary

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.

What data supports the idea that Tamoxifen vs. TamGel for Breast Cancer Risk Reduction is an effective drug?

The available research shows that Tamoxifen can significantly reduce the risk of developing breast cancer. For example, one study found that Tamoxifen can lower the risk by at least 49% in women who are at increased risk. Additionally, it has been shown to help women with certain genetic risks, like BRCA1 or BRCA2 mutations, by reducing the incidence of breast cancer. While there are some risks, such as a small chance of developing endometrial cancer, the benefits of Tamoxifen in reducing breast cancer risk generally outweigh these risks. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Tamoxifen for reducing breast cancer risk?

Research shows that Tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. It is particularly beneficial for women with certain genetic mutations or pre-existing conditions related to breast cancer. ^{1 2 3 4 5}

What safety data exists for Tamoxifen in breast cancer risk reduction?

Tamoxifen, also known as Nolvadex or Tamoxifen citrate, has been studied extensively in clinical trials for breast cancer prevention. Over 24,000 women have participated in these trials, which have identified several adverse effects. In premenopausal women, tamoxifen can cause transient bone loss, while in postmenopausal women, it can lead to uterine effects such as polyps, cysts, and an increased risk of endometrial cancer. The estimated annual risk of endometrial cancer in tamoxifen-treated patients is about 2 per 1,000 women, but these cancers are often detected early and are highly curable. Despite these risks, the benefits of tamoxifen in reducing breast cancer risk, especially in high-risk groups, are considered to outweigh the potential long-term risks. Regular gynecologic evaluations are recommended for women undergoing tamoxifen treatment. ^{2 3 4 5 6}

Is tamoxifen generally safe for humans?

Tamoxifen has been used in large clinical trials and is generally considered safe, but it can have side effects like bone loss in younger women and increased risk of uterine issues, including cancer, in older women. It may also increase the risk of blood clots, so regular medical check-ups are recommended for those taking it. ^{2 3 4 5 7}

Is the drug Tamoxifen a promising treatment for reducing breast cancer risk?

Yes, Tamoxifen is a promising drug for reducing breast cancer risk. It has been shown to lower the risk of developing breast cancer by about 49% in women who are at increased risk. It is especially beneficial for women with certain genetic risks or conditions like BRCA1 or BRCA2 mutations. Tamoxifen is approved for breast cancer risk reduction and is effective in preventing estrogen receptor-positive breast tumors in high-risk women. ^{2 4 5 7 8}

How does the drug Tamoxifen differ from other treatments for breast cancer risk reduction?

Tamoxifen is unique because it is a nonsteroidal antiestrogen drug that reduces the risk of developing breast cancer by blocking estrogen receptors, which is particularly effective in women at high risk for estrogen receptor-positive (ER+) tumors. Unlike some other treatments, it is taken orally and has been shown to reduce breast cancer risk by about 49% in high-risk women, but it also carries risks like endometrial cancer and blood clots. ^{2 4 5 7 8}

What is the purpose of this trial?

This trial is testing two forms of tamoxifen—a low-dose pill and a skin-applied gel. It targets women with conditions that put them at higher risk for breast cancer. The medication works by blocking estrogen, which can help stop cancer cells from growing. Tamoxifen is a well-established treatment for breast cancer, known for its ability to block estrogen receptors and reduce breast cancer incidence.

Research Team

Amy Degnim, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Status of antiestrogen breast cancer prevention trials. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Prescription of tamoxifen for breast cancer prevention by primary care physicians. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

The effect of tamoxifen on the endometrium. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Breast carcinoma chemoprevention in the community setting. Estimating risks and benefits. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Update on breast cancer prevention. [2013]