Hormonal Therapy for Early-Stage Breast Cancer

Recruiting at 7 trial locations

Overseen By Kim Nelson, RN

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: QuantumLeap Healthcare Collaborative

Must be taking: Hormonal therapy

Disqualifiers: Pregnancy, Invasive carcinoma, Gastrointestinal disorders, 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

Compensation: Varies

Number of Visits: 8

Duration: 6 months

400 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this trial is to see if active surveillance monitoring and hormonal therapy in patients diagnosed with ductal cell carcinoma in situ (DCIS), an early stage of breast cancer, can be an effective management of the disease. Participants will be asked to receive control hormonal therapy or an investigational hormonal therapy treatment. Participants will be asked to return for evaluation with MRI at three months and six months. Depending on the evaluation participants will have the option to continue on the treatment. If the evaluation suggests surgery is recommended, the participant will discontinue the study treatment and will undergo surgery. In addition to the treatment and MRI evaluation, participants will be asked to provide blood sample to understand their immune status, provide saliva sample for genetic testing, provide the study with a portion of the tissue or slides generated from tissue removed during surgery performed as part of their standard of care.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, ongoing treatment for DCIS other than what is specified in this protocol is not allowed, so you may need to discuss your current medications with the trial team.

What evidence supports the effectiveness of the drugs used in hormonal therapy for early-stage breast cancer?

Research shows that aromatase inhibitors like anastrozole, letrozole, and exemestane are more effective than tamoxifen in improving disease-free survival for postmenopausal women with hormone-sensitive early breast cancer. Letrozole, in particular, has been shown to reduce the risk of cancer recurrence and improve survival rates when used as an extended therapy after tamoxifen. ^{1 2 3 4 5}

Is hormonal therapy for early-stage breast cancer safe?

Research shows that anastrozole, a type of hormonal therapy, generally has a favorable safety profile compared to tamoxifen for early-stage breast cancer in postmenopausal women. Long-term safety data suggest that while there may be differences in side effects among various hormonal therapies, anastrozole is considered safe for use. ^{1 6 7 8 9}

How does this drug differ from other treatments for early-stage breast cancer?

This drug combination is unique because it includes a mix of aromatase inhibitors (like anastrozole, letrozole, and exemestane) and other hormonal agents (like tamoxifen and testosterone), which have shown to be effective in improving disease-free survival with fewer side effects compared to traditional treatments like tamoxifen alone. ^{9 10 11 12 13}

Eligibility Criteria

This trial is for women aged 18 or older who have been diagnosed with an early stage of breast cancer known as HR+ DCIS, which is hormone receptor positive. They must be willing to provide tumor samples and consent to participate in the study.

Inclusion Criteria

My previous cancer was hormone receptor positive with a biopsy confirming it.

I am a woman and I am 18 years old or older.

You have the willingness and capability to provide tumor samples for research.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hormonal therapy and are evaluated with MRI at 3 and 6 months. Depending on the evaluation, they may continue treatment or undergo surgery.

6 months

3 visits (in-person) at baseline, 3 months, and 6 months

Follow-up

Participants are monitored with alternating MRI and mammogram every 6 months for up to 5 years, followed by annual follow-up for an additional 5 years.

10 years

Biannual visits (in-person) for 5 years, then annual visits

Treatment Details

Interventions

• Anastrazole
• Elacestrant
• Exemestane
• Letrozole
• Tamoxifen
• Testosterone + Anastrazole
• Z-endoxifen

Trial Overview The RECAST Trial is testing whether active surveillance combined with hormonal therapy can effectively manage ductal cell carcinoma in situ (DCIS). Participants will receive either standard hormonal treatments or investigational drugs and undergo MRI evaluations.

Participant Groups

Group I: Testosterone + Anastrazole (T+Ai) Experimental Treatment 1 Intervention

White solid pellet for subcutaneous insertion consisting of 100mg Testosterone and 4mg Anastrazole, an aromatase inhibitor. A cylindrical pellet (4.5mm diameter, 6.35mm diameter) is inserted subcutaneously in the upper outer gluteal region or iliac fossa every 3 months, with treatment up to 36 months. There is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants are followed for an additional 5 years.

Group II: Endoxifen Experimental Treatment 1 Intervention

(Z)-endoxifen is the most active metabolite of the selective estrogen receptor modulator (SERM), tamoxifen. Standard dose: 10mg PO delayed release capsule of z-endoxifen once daily for treatment up to 36 months. same time with a glass of water either 1 hour before a meal or 2 hours after a meal and should not take with alcohol. For patients on this arm there is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants are followed for an additional 5 years.

Group III: Elacestrant Experimental Treatment 1 Intervention

Selective estrogen receptor degrader, Standard dose: 400mg PO with food once daily for treatment up to 36 months. Dose reduction of Elacestrant by up to 2 dose levels permitted depending on toxicity; 400 mg to 300 mg then 300 mg to 200 mg Participants requiring more than 2 dose reductions must discontinue treatment For patients on this arm there is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants are followed by for an additional 5 years.

Group IV: chemoprevention therapy per investigator choice Active Control 4 Interventions

a. For premenopausal women: 20 mg or 5 mg tamoxifen orally b. for postmenopausal women: standard oral doses of AI of choice: exemestane 25 mg daily, letrozole 2.5 mg daily, or anastrozole 1 mg daily; or reduced exemestane dosing: 25 mg 3 times per week orally i. For postmenopausal women who are not tolerating an AI, low dose (5 mg) or standard dose (20 mg) of tamoxifen There is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants may continue treatment for up to 5 years.

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

Approved in European Union as Arimidex for:

• Early breast cancer
• Advanced breast cancer

Approved in United States as Arimidex for:

• Postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Japan as Arimidex for:

• Postmenopausal women with hormone receptor-positive early breast cancer
• Postmenopausal women with hormone receptor-positive recurrent breast cancer

Who Is Running the Clinical Trial?

QuantumLeap Healthcare Collaborative

Lead Sponsor

Trials

6

Recruited

7,000+

Findings from Research

Anastrozole and letrozole are effective oral treatments for advanced breast cancer in postmenopausal women, especially when other therapies like tamoxifen have not worked.

Both drugs are claimed to be more effective and less toxic than the standard treatment, megestrol acetate, although the review assesses the validity of these claims.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

Tamoxifen is the standard treatment for postmenopausal women with hormone-sensitive early breast cancer, but it has side effects that have led researchers to look for safer alternatives.

Third-generation aromatase inhibitors like anastrozole, letrozole, and exemestane have shown better efficacy and a more favorable side effect profile compared to tamoxifen in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. Grana, G.[2018]

Letrozole is an effective treatment for postmenopausal women with early-stage or advanced hormone-sensitive breast cancer, showing a 43% reduction in disease recurrences when used as extended adjuvant therapy beyond standard tamoxifen treatment.

In advanced breast cancer, letrozole outperformed tamoxifen in terms of time to disease progression (9.4 months vs. 6.0 months) and has a similar tolerability profile, making it a recommended first-line therapy according to treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in postmenopausal women with breast cancer. Simpson, D., Curran, MP., Perry, CM.[2018]

Aromatase inhibitors (AIs) like anastrozole, exemestane, and letrozole provide longer disease-free survival (DFS) compared to tamoxifen for women with early breast cancer, based on a review of multiple trials.

AIs are well tolerated and have a different safety profile than tamoxifen, making them a favorable option for initial adjuvant therapy or as a switch from tamoxifen after 2-3 years, especially for node-positive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choosing early adjuvant therapy for postmenopausal women with hormone-sensitive breast cancer: aromatase inhibitors versus tamoxifen. Carpenter, R.[2018]

In a study involving 6182 postmenopausal women with hormone-receptor-positive breast cancer, sequential treatment with tamoxifen and letrozole did not significantly improve disease-free survival compared to letrozole monotherapy, indicating that letrozole alone may be sufficient for treatment.

The updated analysis showed no statistically significant difference in overall survival between letrozole and tamoxifen monotherapy, suggesting that both treatments have similar long-term outcomes, with adverse events consistent with previous reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., et al.[2022]

The ATAC trial, involving over 9,000 postmenopausal women, demonstrated that anastrozole significantly improves disease-free survival and reduces recurrence rates compared to tamoxifen, with benefits continuing even after treatment ends.

Anastrozole also has a favorable safety profile compared to tamoxifen, suggesting it may be a better initial treatment option for early breast cancer, especially when considering long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. Buzdar, AU., Cuzick, J.[2018]

The FACE trial is a large-scale study involving 4000 postmenopausal women with hormone receptor-positive, node-positive breast cancer, comparing the efficacy and safety of letrozole and anastrozole over a treatment period of up to 5 years.

The primary goal of the trial is to assess disease-free survival (DFS), while secondary objectives include evaluating overall survival (OS) and the time to distant metastases, which will provide comprehensive insights into the effectiveness of both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FACE trial: letrozole or anastrozole as initial adjuvant therapy? Jonat, W., Mundhenke, C.[2018]

In a study of 6241 postmenopausal women with early-stage breast cancer, anastrozole was found to have significantly fewer treatment-related adverse events compared to tamoxifen, indicating better tolerability.

Anastrozole also demonstrated a more favorable risk-benefit profile, with lower rates of serious adverse events and recurrence compared to tamoxifen, making it a preferable option for adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Buzdar, A., Howell, A., Cuzick, J., et al.[2022]

Third-generation aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane have emerged as effective alternatives to tamoxifen for treating postmenopausal breast cancer, particularly in hormone receptor-positive cases, as shown in the ATAC trial with over five years of follow-up.

Fulvestrant, a new type of estrogen receptor antagonist with no partial agonist activity, represents a promising option in breast cancer treatment, and the review discusses future sequencing strategies for using AIs earlier in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of postmenopausal breast cancer. Howell, A.[2018]

Adjuvant hormonal therapy with tamoxifen significantly reduces the risk of breast cancer recurrence and death in women with early-stage, hormone receptor-positive breast cancer, but it also carries risks of endometrial cancer and thromboembolic events.

Recent trials, including the MA-17 and Intergroup Exemestane Study, show that selective aromatase inhibitors (AIs) like anastrozole and exemestane provide superior disease-free survival compared to tamoxifen, establishing AIs as a preferred treatment option for postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know? Chung, CT., Carlson, RW.[2019]

Third-generation aromatase inhibitors, like anastrozole, letrozole, and exemestane, show significant antitumor activity in breast cancer treatment and have fewer side effects compared to tamoxifen.

Anastrozole has been found to be more effective than tamoxifen for postmenopausal women receiving adjuvant endocrine therapy, highlighting its potential as a preferred treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in breast cancer therapy. Buzdar, AU.[2019]

Anastrozole and letrozole significantly improve disease-free survival compared to tamoxifen in postmenopausal women with early-stage breast cancer, based on results from Phase III trials.

Switching to an aromatase inhibitor like anastrozole or exemestane after 2 to 3 years of tamoxifen therapy reduces the risk of cancer recurrence more effectively than continuing tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer. Berry, J.[2007]

The ATAC trial is one of the few studies that directly compares aromatase inhibitors (AIs) for breast cancer treatment, providing valuable insights into their effectiveness.

Emerging evidence suggests a proposed sequence of hormonal therapies, including anastrozole and tamoxifen, tailored for different patient populations, which could optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy in early and advanced breast cancer. Buzdar, AU.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

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

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in postmenopausal women with breast cancer. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Choosing early adjuvant therapy for postmenopausal women with hormone-sensitive breast cancer: aromatase inhibitors versus tamoxifen. [2018]

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

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. [2022]

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

Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. [2018]

7. England pubmed.ncbi.nlm.nih.gov

The FACE trial: letrozole or anastrozole as initial adjuvant therapy? [2018]

8. England pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. [2022]

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

New developments in the treatment of postmenopausal breast cancer. [2018]

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

Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know? [2019]

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

Aromatase inhibitors in breast cancer therapy. [2019]

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

Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer. [2007]

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

Hormonal therapy in early and advanced breast cancer. [2019]