PRESTO: A Study to See Whether Estrogen Can Slow the Growth of Some ER Positive Breast Cancers

Sponsor

AHS Cancer Control Alberta (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02238808

Collaborator

(none)

Enrollment

Location

Arm

137

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Estrogen Receptor Positive Breast Cancer	Drug: Estradiol	Phase 2

Detailed Description

Breast cancer is a heterogeneous disease that includes two ER+ genetic subtypes (luminal A and luminal B) that differ in their response to treatment.

Results from the Women's Health Initiative Trial showed that estrogen treated hysterectomized women with no prior history of breast cancer had a significant and persistent decrease in breast cancer incidence when compared to placebo treated participants. This implies that some ER+ breast cancers are in fact growth inhibited by estrogens and are not growth promoted.

The hypothesis of this study is that some ER+ breast cancers (luminal A) are actually sensitive (growth inhibited) by estrogen.

Objectives:

To assess changes in breast cancer proliferation after a 7-14 day trial of estradiol in newly diagnosed estrogen receptor positive post-menopausal breast cancer patients prior to surgery.
Exploratory analysis of biologic correlates with comparison to available genotyping tests.

This is an open-label single group assignment pilot study for safety/efficacy and exploratory biologic correlates

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

PRe-operative ESTradiOl Window of Opportunity Study in Post-Menopausal Women With Newly Diagnosed ER Positive Breast Cancer

Study Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Jul 30, 2018

Anticipated Study Completion Date :

Jan 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Estradiol treatment Estradiol 6 mg daily for 7-14 days	Drug: Estradiol Eligible participants will take 2 mg Estradiol 3 times daily for 7-14 days pre-surgery. Other Names: estrogen

Arm

Intervention/Treatment

Experimental: Estradiol treatment

Estradiol 6 mg daily for 7-14 days

Drug: Estradiol

Eligible participants will take 2 mg Estradiol 3 times daily for 7-14 days pre-surgery.

Other Names:

estrogen

Outcome Measures

Primary Outcome Measures

To assess changes in breast cancer proliferation after a 7-14 day trial of estradiol in newly diagnosed estrogen receptor positive post-menopausal breast cancer patients prior to surgery. [end of 7-14 day treatment with estradiol]

Secondary Outcome Measures

Exploratory analysis of biologic correlates with comparison to available genotyping tests [end of 7-14 day treatment with estradiol]
Analysis of recurrence/survival data based on initial Ki67 response to 7-14 day trial of estradiol. [10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female gender
Estrogen receptor positive (ER+) breast cancer
HER2 negative breast cancer
Post-menopausal by greater than 5 years
No previous hormonal replacement therapy
Low to intermediate histologic grade
ECOG Performance status of 0 of 1
Adequate hematological, renal and hepatic function is required
Ability to take oral medication
Patient must have adequate tissue for diagnosis, biomarkers and Ki67 assays

Exclusion Criteria:

Pre-menopausal women
Locally advanced or metastatic breast cancer
Current, previous or planning for pre-operative treatment with chemotherapy, hormone therapy including corticosteroids, radiation therapy for malignancy or other condition
Known hypersensitivity or intolerance to estradiol
Ischemic changes on baseline electrocardiogram
Symptomatic but untreated cholelithiasis
History of deep vein thrombosis, pulmonary embolism, stroke, acute myocardial infarction, congestive cardiac failure, untreated hypertension or known inherited hypercoagulable disorder
Undiagnosed abnormal vaginal bleeding or prior history of endometrial cancer
Untreated metabolic disturbances (glucose > 15.0 mmol/L and triglycerides > 400 mg/dL)
Current treatment with drugs known to be moderate or strong inhibitors of inducers of isoenzyme CYP3A4
The time between study enrolment and definitive breast surgery is not sufficient for administration of at least 7 days of estradiol