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Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

36 Participants Needed

Estradiol for Advanced Breast Cancer
(ESTHER Trial)

Overseen ByResearch Nurse

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dartmouth-Hitchcock Medical Center

Must not be taking: Investigational therapies

Disqualifiers: CNS disease, Thrombosis, Stroke, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Prior Safety DataThis treatment has passed at least one previous human trial

Approved in 3 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of estradiol, a form of hormone therapy, for women with advanced breast cancer. Researchers aim to determine if women with specific genetic changes in their cancer benefit more from this treatment. The treatment involves using 17b-estradiol until the cancer progresses. Women who are post-menopausal, have estrogen-receptor positive (ER+) breast cancer that has spread or recurred, and have tried at least one other hormone-based therapy might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking any current anti-cancer therapies during the study, except for Trastuzumab and anti-resorptive bone therapies, which are allowed. If you are on any investigational cancer therapy, you must have stopped it at least 3 weeks before joining the trial.

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

Research has shown that estradiol, a type of estrogen, is under study as a treatment for advanced breast cancer. Some studies suggest it might increase breast cancer risk due to its effect on hormone levels. However, in certain forms like creams or vaginal treatments, it hasn't significantly increased cancer recurrence in survivors.

The current trial is in Phase 2, indicating that the treatment has passed initial safety tests. This suggests estradiol is generally safe, but researchers continue to gather detailed safety information. Participants should carefully consider the potential risks and benefits before joining the trial.¹ ² ³ ⁴ ⁵

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced breast cancer, which often include hormone therapies like tamoxifen or aromatase inhibitors, Estradiol offers a unique approach by utilizing a form of estrogen itself. This treatment is particularly intriguing because it works by exploiting the cancer's reliance on low estrogen levels, potentially causing the cancer cells to stop growing. Researchers are excited because Estradiol could provide a new option for patients whose cancers have become resistant to other hormone therapies, offering a possible new avenue for those with limited alternatives.

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

Research has shown that estradiol, a type of estrogen, may offer benefits in treating breast cancer. Some studies found that using vaginal estrogen in breast cancer survivors does not increase the risk of cancer recurrence. In fact, these studies suggest it may help some patients live longer. Estradiol interacts with hormone receptors in the body, potentially affecting cancer cell growth. While concerns exist about estrogen and cancer risk, the specific effects of estradiol on advanced breast cancer, especially in individuals with certain genetic traits, remain under investigation. In this trial, participants will receive 17b-estradiol until disease progression. These findings suggest estradiol might benefit some individuals with advanced breast cancer.¹ ⁴ ⁶ ⁷ ⁸

Who Is on the Research Team?

Mary D. Chamberlin

Principal Investigator

Dartmouth-Hitchcock Medical Center

Are You a Good Fit for This Trial?

This trial is for post-menopausal women with ER+ advanced breast cancer who have tried at least one endocrine therapy before. It's not suitable for those with a recent heart attack, congestive heart failure, high-risk previous cancers, stroke history, brain metastases unless stable for 3 months, or a history of blood clots.

Inclusion Criteria

My cancer has spread or returned and cannot be cured with treatment.

I am a post-menopausal woman with estrogen receptor-positive breast cancer.

I have had hormone therapy for advanced cancer.

Exclusion Criteria

Any investigational cancer therapy in the last 3 weeks

I am not on cancer treatments except possibly Trastuzumab or bone therapies.

My brain condition has been stable for at least 3 months.

See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients will be treated with 17b-estradiol until disease progression

Up to 12 months

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Observational Phase (optional)

After disease progression on 17b-estradiol, patients will be treated at their oncologist's discretion

Until further disease progression

What Are the Treatments Tested in This Trial?

Interventions

Estradiol

Trial Overview The ESTHER study is testing if estradiol treatment benefits patients whose breast cancer has specific ESR1 mutations more than those without these mutations. No other anti-cancer treatments are allowed during the trial except certain bone therapies and Trastuzumab in some cases.

How Is the Trial Designed?

1Treatment groups

Experimental Treatment

Group I: Treatment ArmExperimental Treatment1 Intervention

Treatment Phase: Patients will be treated with 17b-estradiol until disease progression. At this point, the patient will end protocol therapy

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

Approved in European Union as Estradiol for:

Menopausal symptoms
Hypoestrogenism
Osteoporosis prevention
Breast cancer palliation
Prostate cancer palliation

Approved in United States as Estradiol for:

Moderate to severe vasomotor symptoms due to menopause
Vulvar and vaginal atrophy due to menopause
Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
Prevention of postmenopausal osteoporosis
Palliative treatment of breast cancer
Palliative treatment of prostate cancer

Approved in Canada as Estradiol for:

Menopausal symptoms
Hypoestrogenism
Osteoporosis prevention
Breast cancer palliation
Prostate cancer palliation

Find a Clinic Near You

Who Is Running the Clinical Trial?

Dartmouth-Hitchcock Medical Center

Lead Sponsor

Trials

548

Recruited

2,545,000+

Published Research Related to This Trial

The 7-day estradiol transdermal patch (Climara) effectively reduces hot flushes in women, with a mean decline of 74.6% for the higher dose compared to 64.5% for the lower dose, showing comparable efficacy to traditional hormone therapies.

The Climara patch is well tolerated, with a low withdrawal rate due to adverse events (8.9%), primarily related to skin reactions, and it demonstrated better adhesion compared to other patches, making it a practical option for estrogen replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with a seven-day estradiol transdermal system for estrogen replacement therapy.Gordon, SF.[2019]

Anastrozole significantly improves survival and tolerability in postmenopausal women with advanced breast cancer compared to megestrol acetate, and it also prolongs time to progression compared to tamoxifen in first-line therapy for hormone receptor-positive (HR+) disease.

In the adjuvant setting, anastrozole shows superior efficacy and tolerability over tamoxifen, making it a preferred treatment option for HR+ early breast cancer, and it also reduces the risk of contralateral breast cancer, suggesting its potential as a chemopreventive agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of anastrozole across the breast cancer continuum: from advanced to early disease and prevention.Nabholtz, JM.[2018]

A comprehensive safety review of Estratest and Estratest HS, based on over 1 million woman-years of exposure from 1989 to 1996, found no significant safety concerns, with only 863 adverse events reported, which is relatively low given the extensive use.

The most common adverse events were typical of estrogen and androgen therapies, such as weight gain and headaches, and serious adverse events were rare, indicating that these medications are safe when used as directed, with manageable risks associated with their androgen component.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States.Phillips, E., Bauman, C.[2019]

Citations

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

Vaginal estrogen use in breast cancer survivorsThe 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.

2.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC12254641/

Vaginal health in breast cancer survivors: a practical clinical ...This article reviews the effects of low estrogen on the genital and urinary systems and offers updated guidelines on how to diagnose and treat ...

3.ascopubs.orgascopubs.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 ...

4.annalsofoncology.organnalsofoncology.org/article/S0923-7534(24)04880-4/fulltext

Estrogens and breast cancerEstrogen may increase breast cancer risk by inducing the progesterone receptor and augmenting progesterone signaling.

5.sciencedirect.comsciencedirect.com/science/article/pii/S0960977624001498

Clinical significance of serum estradiol monitoring in ...A total of 706 patients were enrolled, including 482 women with OFS in combination with AI. Among them, 116 women (16.4 %) exhibited E2 levels exceeding 2.72 pg ...

6.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC9452594/

Hormone Therapy and Risk of Breast CancerEstradiol heightens the risk of breast cancer in postmenopausal women and preclinical studies have demonstrated that progestin engenders progenitor cells in ...

7.sciencedirect.comsciencedirect.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.

8.ascopubs.orgascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e24049

Safety and serum estradiol levels in hormonal treatments ...The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms.

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