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

19 Participants Needed

Trial Summary

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 estrogen treatment generally safe for humans?

The safety of estrogen treatments like Estradiol has been evaluated in various studies, often focusing on their use in breast cancer prevention. While these treatments can be effective, they may also cause side effects such as vasomotor symptoms (hot flashes), musculoskeletal issues, and vulvovaginal symptoms. It's important to weigh these potential side effects against the benefits when considering estrogen therapy. ^{1 2 3 4 5}

How does the drug estrogen differ from other treatments for breast cancer?

Estrogen treatment for breast cancer is unique because it involves using the hormone itself, which is different from other hormonal therapies like aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs) that either block estrogen production or its effects. This approach is less common and may be considered when other standard treatments are not suitable. ^{6 7 8 9 10}

What is the purpose of this trial?

Some breast cancers have estrogen receptors (ER+). The investigators know that some ER+ tumours can be cured by hormone therapy alone while other ER+ breast cancers cannot. Currently, there is no perfect way to tell these groups apart nor do the investigators know why some respond when others do not. Research findings suggest that the two types of ER+ breast cancers differ in their response to estrogen with estrogen being toxic to one type and not the other. For those tumours that find estrogen toxic, this may explain why tumours only start to grow when estrogen levels decrease after menopause. The purpose of this study is to see whether a two-week treatment of estrogen equal to pre-menopausal estrogen levels will decrease the rate at which patients' ER+ tumours grow. This will be done by comparing the growth rate in the tissue removed during standard of care surgery after patients have been treated with 7-14 days of estrogen prior to that surgery.

Research Team

Judith Hugh, MD

Principal Investigator

University of Alberta

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

References

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

Phase 3 trials of aromatase inhibitors for breast cancer prevention: following in the path of the selective estrogen receptor modulators. [2009]

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

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

3. United States 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. [2023]

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

Preventive therapy for breast cancer. [2022]

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

Specific adverse events predict survival benefit in patients treated with tamoxifen or aromatase inhibitors: an international tamoxifen exemestane adjuvant multinational trial analysis. [2022]

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

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

7. 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]

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

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The effects of adjuvant hormonotherapy on tear functions in patients with breast cancer. [2021]

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

Anastrozole as adjuvant therapy for early-stage breast cancer: implications of the ATAC trial. [2019]