Estrogen for Breast Cancer

(PRESTO Trial)

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: AHS Cancer Control Alberta

Must be taking: Estrogen

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Pre-menopausal, Metastatic cancer, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a potential new treatment for a specific type of hormone-reliant breast cancer. Researchers aim to determine if two weeks of estrogen treatment can slow the growth of certain estrogen receptor-positive (ER+) tumors, which may respond differently to hormones. The treatment involves a daily dose of estradiol, a form of estrogen, before surgery to assess if the cancer's growth rate decreases. Women who are post-menopausal for more than five years with ER+ and HER2-negative breast cancer, and who have not received hormone therapy before, might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in breast cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently on hormone therapy, chemotherapy, or certain other treatments. It's best to discuss your specific medications with the trial team.

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

Research has shown that using estradiol, a type of estrogen, does not increase the risk of breast cancer recurrence or severity. For instance, studies on vaginal estrogen therapy, applied directly to the vaginal area, have indicated no increase in early breast cancer deaths. This suggests it does not worsen breast cancer.

In some cases, breast cancer patients using certain forms of estrogen have demonstrated better survival rates, suggesting that estrogen might not only be safe but could even be beneficial. However, the estrogen used in these studies is often applied to the skin or used vaginally, differing from the oral estradiol being tested in the trial.

The trial is in an early stage, so more information is needed about the safety of oral estradiol for this specific use. Nonetheless, these findings provide some reassurance about the safety of estrogen in the context of breast cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about using estradiol for breast cancer because it offers a different approach than the standard treatments like hormone blockers or chemotherapy. Unlike these treatments, which often work by suppressing estrogen to slow cancer growth, estradiol uses the hormone itself to disrupt cancer cell survival. This approach is intriguing because estradiol can paradoxically kill certain breast cancer cells after initial exposure, potentially offering a quicker response in just 7 to 14 days. This unique mechanism could provide an alternative for patients who have become resistant to other hormone therapies.

What evidence suggests that this treatment might be an effective treatment for breast cancer?

Research has shown that some types of breast cancer, known as estrogen receptor-positive (ER+) cancers, might be harmed by estrogen. Certain ER+ tumors appear to find estrogen toxic, which may explain their growth when estrogen levels drop after menopause. In this trial, participants will receive estradiol treatment to determine if increasing estrogen levels to pre-menopausal levels can slow these tumors within a few weeks. Although predicting which ER+ cancers will react this way is not yet precise, the approach is based on understanding how different tumors respond to estrogen. Previous studies demonstrated that estradiol does not increase the risk of cancer recurrence, supporting its safe use for this purpose. ^{1 2 3 5 6}

Who Is on the Research Team?

Judith Hugh, MD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for post-menopausal women over 5 years with ER+ breast cancer that hasn't spread, no prior hormone therapy, and can take pills. They must have good physical function and organ health but cannot be on certain drugs or have a history of blood clots or heart issues.

Inclusion Criteria

I am female.

I am fully active or able to carry out light work.

My breast cancer is not HER2 positive.

Exclusion Criteria

You have had a bad reaction or can't tolerate estradiol.

Your baseline electrocardiogram shows signs of reduced blood flow to the heart.

I am a woman who has not gone through menopause.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive estradiol treatment at 6 mg daily for 7-14 days prior to surgery

1-2 weeks

Surgery

Standard of care surgery is performed after the treatment phase

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol

Trial Overview The study tests if estrogen at pre-menopausal levels given for 7-14 days before surgery can slow the growth of some ER+ breast cancers by comparing tumor growth rates in removed tissue.

How Is the Trial Designed?

Group I: Estradiol treatment Experimental Treatment 1 Intervention

Estradiol 6 mg daily for 7-14 days

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Published Research Related to This Trial

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]

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]

Tamoxifen effectively reduces the risk of estrogen receptor-positive breast cancer by at least 50% in both pre- and postmenopausal women, highlighting its efficacy as a preventive treatment.

Newer agents like aromatase inhibitors have shown even greater reductions in breast cancer risk (up to 65% with exemestane and 60% with anastrozole) for postmenopausal women, but there is a need for more targeted therapies for premenopausal women with estrogen receptor-negative breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventative therapies for healthy women at high risk of breast cancer. Sestak, I.[2020]

In a study of 337 postmenopausal women with ER and/or PgR positive breast cancer, letrozole demonstrated a significantly higher overall objective response rate (55%) compared to tamoxifen (36%) after four months of treatment.

Letrozole also showed superior results in secondary endpoints, including ultrasound response (35% vs. 25%) and mammographic response (34% vs. 16%), while both treatments were well tolerated, indicating letrozole's effectiveness as a preoperative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Eiermann, W., Paepke, S., Appfelstaedt, J., et al.[2022]

In a study of 3,046 postmenopausal women with ductal carcinoma in situ, 28.5% discontinued treatment with anastrozole or tamoxifen, with specific adverse events like thrombosis and arthralgia linked to discontinuation of both drugs.

Patient-reported outcomes (PROs) such as pain interference and hot flashes were significant factors in discontinuing tamoxifen, while only hot flashes were associated with discontinuation of anastrozole, highlighting the importance of both adverse events and patient experiences in treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity Index, Patient-Reported Outcomes, and Early Discontinuation of Endocrine Therapy for Breast Cancer Risk Reduction in NRG Oncology/NSABP B-35. Henry, NL., Kim, S., Hays, RD., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37917089/

Vaginal Estrogen Therapy Use and Survival in Females ... Results of this study showed no evidence of increased early breast cancer-specific mortality in patients who used vaginal estrogen therapy ...

2. ajog.org ajog.org/article/S0002-9378(24)01126-8/fulltext

Vaginal estrogen use in breast cancer survivors The use of vaginal estrogen in patients with a history of breast cancer does not appear to be associated with an increased risk of breast cancer recurrence.

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2811413

Vaginal Estrogen Therapy Use and Survival in Breast Cancer Results of this study showed no evidence of increased early breast cancer–specific mortality in patients who used vaginal estrogen therapy compared with ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.578

Use of local estrogen therapy among breast cancer ... Conclusions: The use of vaginal estrogen among this SEER-MHOS cohort of breast cancer patients showed improved survival outcomes. These findings ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39521301/

Vaginal estrogen use in breast cancer survivors Conclusion: The use of vaginal estrogen in patients with a history of breast cancer does not appear to be associated with an increased risk of breast cancer ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225000027

Safety of topical estrogen therapy during adjuvant ... Topical oestrogen use does not appear to increase recurrence or mortality risk in breast cancer survivors on tamoxifen.