Tamoxifen vs. TamGel for Breast Cancer Risk Reduction

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Amy Degnim, M.D.

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Amy C. Degnim

No Placebo Group

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

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.

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.

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 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 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}

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.

Treatment Details

Interventions

• Tamoxifen (Selective Estrogen Receptor Modulator)

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, Australia 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

🇦🇺 Approved in Australia as Tamoxifen for:

• Breast cancer
• Infertility
• Gynecomastia

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

MD Anderson Cancer center at Cooper Camden, NJ

Northwestern University Evanston, IL

Mayo Clinic Rochester, MN

Who Is Running the Clinical Trial?

Amy C. Degnim Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

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

Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. [2019] Tamoxifen citrate (Nolvadex [Great Britain]; no comparable US product) is a recently developed antiestrogen with significant activity against metastatic breast cancer in postmenopausal women. We investigated its usefulness in breast cancer patients after conventional endocrine therapy and combination chemotherapy had failed. Of the 50 evaluable patients, four (8%) achieved a complete remission, 14 (28%) achieved a partial remission, and ten showed a less than partial response or stabilization of their disease. Median duration of response was eight months, and the survival of responders was significantly prolonged compared to that of the nonresponders. Side effects of the treatment were mild. These results demonstrate that tamoxifen offers the best choice of therapy for patients with metastatic breast cancer after conventional endocrine therapy and combination chemotherapy have failed.

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

Status of antiestrogen breast cancer prevention trials. [2016] Various ongoing double-blind clinical trials are evaluating the use of tamoxifen (Nolvadex) as chemoprevention for breast cancer. A total of over 24,000 healthy women have been randomized to these trials, and it should be possible, by the year 2000, to detect any preventive effect of tamoxifen in healthy women. Furthermore, with the large numbers of women involved, it should be possible to evaluate prevention in subgroups of participants according to risk of the disease, particularly those women carrying high-risk genes, such as BRCA1 and BRCA2. Adverse effects of tamoxifen have been identified, including a transient bone loss in premenopausal women and uterine effects, including polyps, cysts, and endometrial cancer, in postmenopausal women. Although the potential benefit of tamoxifen in preventing breast cancer in healthy women is likely to outweight any potential long-term risks, the use of other tamoxifen-like drugs, such as raloxifene (Evista) and toremifene (Fareston) is now being investigated.

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

Prescription of tamoxifen for breast cancer prevention by primary care physicians. [2015] Although tamoxifen citrate has been approved for primary reduction of breast cancer risk since 1998, little is known about the prescription of tamoxifen by primary care physicians.

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

The effect of tamoxifen on the endometrium. [2013] Tamoxifen (Nolvadex), a nonsteroidal antiestrogen, was first approved by the FDA for the treatment of patients with breast cancer in 1978. Large clinical trials have demonstrated a recurrence-free and overall survival benefit in both pre- and postmenopausal women. Long-term adjuvant tamoxifen is the endocrine treatment of choice for selected patients with breast cancer, and large-scale trials are currently underway to evaluate its role as a chemopreventive agent in healthy women at risk for breast cancer. Consequently, a large number of women will be subjected to both the benefits and potential risks of long-term tamoxifen therapy. One of the most significant potential complications is the development of endometrial cancer. The estimated annual risk of endometrial cancer in tamoxifen-treated patients is approximately 2 per 1,000 women. Most of these cancers will be detected at an early stage when they are highly curable. The potential benefit of tamoxifen treatment in breast cancer patients outweighs this risk; however, all patients receiving tamoxifen should undergo regular gynecologic evaluations.

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

Reducing the risk of breast cancer with tamoxifen in women at increased risk. [2013] Validated quantitative models are available that permit the accurate estimation of a woman's risk of developing invasive breast cancer during a specified period of time. Data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial indicate that tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. All premenopausal women whose 5-year risk of developing breast cancer is 1.67% or greater derive a net benefit from taking tamoxifen for risk reduction. Women who have either lobular carcinoma-in-situ or atypical ductal or lobular hyperplasia derive an even greater net benefit. Women who carry mutations in either the BRCA1 or BRCA2 gene will also experience reduced incidence of breast cancer with tamoxifen. Although postmenopausal women derive a net benefit from tamoxifen through the reduction of both breast cancer and bone fracture event rates, the risks of both invasive endometrial cancer and thromboembolic events must be balanced in older women. Physicians should identify appropriate candidates with whom to discuss the possible benefits of tamoxifen for reducing the risk of breast cancer.

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

Breast carcinoma chemoprevention in the community setting. Estimating risks and benefits. [2015] The United States Preventive Services Task Force recommends that women who are at both high risk for breast carcinoma and low risk for adverse events should receive counseling regarding tamoxifen for chemoprevention. Estimates of the risks and benefits of tamoxifen based on results from clinical trials may not reflect the real-world experience. The authors determined the prevalence of women in a community-based cohort who would meet the definition of high risk for breast carcinoma and calculated the number of women needed to screen to determine one for whom the benefits of tamoxifen would outweigh the risks. Baseline incidence also was examined for adverse health events in this community-based cohort compared with participants in the Breast Cancer Prevention Trial.

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

Update on breast cancer prevention. [2013] Four randomized prospective trials have evaluated tamoxifen for chemoprevention of breast cancer. The National Surgical Adjuvant Breast and Bowel Project P-1 trial reported that tamoxifen reduced the risk of invasive breast cancer by 49%. Two smaller European trials, the Royal Marsden Hospital Chemoprevention Trial and the Italian Tamoxifen Prevention Study, demonstrated no decrease in the incidence of breast cancer among women using tamoxifen. The International Breast Cancer Intervention Study confirmed that tamoxifen can reduce the risk of breast cancer in healthy women. The Multiple Outcomes of Raloxifene Evaluation trial, which evaluated the use of raloxifene (Evista) to prevent osteoporosis, found that the risk of invasive breast cancer decreased by 76%. A uniform theme in these trials is that tamoxifen reduces the risk of breast cancer among women at high risk for the disease. Tamoxifen is currently approved for breast cancer risk reduction. However, because of the side effects associated with its use (i.e., endometrial cancer and thromboembolism), other agents are being investigated. The Study of Tamoxifen and Raloxifene is designed to compare the efficacy of tamoxifen and raloxifene in reducing breast cancer risk. Aromatase inhibitors will also be studied in the setting of chemoprevention for breast cancer.

8. 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] Tamoxifen improves outcome in women with breast cancer and reduces the incidence of estrogen receptor-positive (ER+) breast tumors in prevention trials. Tamoxifen use is associated with an increased risk of potentially serious adverse events, principally endometrial cancer and venous thromboembolic events and, therefore, detailed knowledge of the effects of tamoxifen is important. With more cases of breast cancer being found as the follow-up time increases, it is now possible to perform more detailed analysis of the Italian Randomized Trial of Tamoxifen. Women with hysterectomy (N = 5408) were randomly assigned to receive 20 mg tamoxifen per day (N = 2700) or placebo (N = 2708). After a median of 81.2 months of follow-up, 79 case subjects (34 in the tamoxifen arm and 45 in the placebo arm) were diagnosed with breast cancer. We were able to identify a group of women at increased risk of ER+ breast cancers (high-risk group) on the basis of baseline as well as reproductive and hormonal characteristics (height, age at menarche, parity, age at first birth, and oophorectomy). Tamoxifen administered to women in the high-risk group showed statistically significantly reduced incidence of breast cancer (tamoxifen, 3 and placebo, 15; P =.003), but no such effect was seen in the low-risk group (tamoxifen, 31 and placebo, 30; P =.89). The positive effect of tamoxifen on breast cancer among high-risk women is most marked for ER+ tumors (tamoxifen, 1 and placebo, 11; P =.002). Chemoprevention of breast cancer with tamoxifen appears to be effective in women at high risk of ER+ tumors but not among women at low risk, who may well be protected naturally by late age at menarche or early first pregnancy, or artificially by removal of the ovaries. Tamoxifen could be offered as a preventive agent to women identified at high-risk of breast cancer because of hormone-related risk factors. Such a strategy would greatly reduce the numbers of women who would need to take tamoxifen to obtain the same absolute reduction in breast cancer. These findings are exploratory and need to be confirmed in other randomized trials.