Investigating the Impact of Tamoxifen Therapy on Ovarian Aging

Ovarian toxicity is a well-described side effect of traditional chemotherapy in premenopausal women receiving treatment for early stage breast cancer. However, the impact of long-term endocrine therapy on ovarian function is not established, and to our knowledge, has never been directly studied. Understanding the effects of hormone therapy on ovarian aging will help breast cancer patients of reproductive age make more informed and empowered decisions regarding their treatment. The purpose of this study is to explore the relationship between tamoxifen therapy and ovarian aging. Patients will be identified through the UCSF Cancer Registry and California Pacific Medical Center Cancer Registry and will be evaluated based on age and menopausal status. Women who read about the study from clinicaltrials.gov and contact the study coordinator will also be considered for enrollment. The age of menopause onset will be assessed through surveys and will be compared to the accepted national average age of natural menopause. Biomarkers of ovarian reserve will be assessed in premenopausal women between ages 25-45 and will be compared to those of healthy age- and ethnicity-matched premenopausal controls from an ongoing RO1- funded prospective longitudinal ovarian aging (OVA) study.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Fertility

• Study Type: Observational
• Enrollment (Actual): 266

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

The UCSF Cancer Registry will be screened for female patients who were treated at the UCSF Breast Care Center between 1985 and 2010 and who meet the eligibility criteria listed below.

Description

Inclusion Criteria

1. Female
2. ≥25 years of age at the time of study enrollment
3. Diagnosed with stage I-III invasive breast cancer or ductal carcinoma in situ, or determined to be high risk for primary breast cancer

4. If endocrine therapy was used, women must have completed at least 2 years of endocrine therapy as defined by either

   1. Tamoxifen alone
   2. Ovarian suppression plus tamoxifen or aromatase inhibitor
   3. Ovarian suppression alone
5. Women must have been premenopausal at the time of endocrine therapy initiation. Premenopausal is defined as having had a menstrual cycle within 12 months before starting treatment.
6. For the biomarker assessments, patients must be off all endocrine therapy (tamoxifen, ovarian suppression with goserelin or leuprolide, or aromatase inhibitor) for at least 6 months prior to study enrollment.
7. For the biomarker assessments, patient must be off hormone contraceptives, fertility treatments, or other hormone therapies for at least 3 months prior to study enrollment
8. For the biomarker assessments, patient must have had regular periods the last 3 months.

Exclusion Criteria

1. Evidence for either local recurrence following use of adjuvant systemic therapy or evidence for distant recurrence of breast cancer.
2. Prior history of ovarian surgery or manipulation
3. Mother with premature ovarian failure as defined by onset of menopause at age <40
4. Prior chemotherapy exposure
5. Prior history of endometriosis, anovulation or documented infertility
6. Pregnant at the time of study enrollment

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
history of hormone therapy
no history of hormone therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
age of menopause onset	The primary aim of this study is to determine the mean age of menopause onset in a cohort of women who have completed a course of tamoxifen therapy and to compare this age with the accepted national average age of natural menopause. Age of menopause onset which is defined as the year of the last menstrual period minus patient's birth year.	assessed at time of reproductive history survey (30 minutes long, one-time assessment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
biomarkers of ovarian reserve	A secondary aim is to compare biomarkers of ovarian reserve in premenopausal women between ages 25-45 who have been previously treated with tamoxifen with those of age- and ethnicity-matched healthy controls. The primary biomarker of interest is antral follicle count (AFC). Other biomarkers that will be measured include anti-Mullerian hormone (AMH), inhibin B, FSH, and estradiol levels.	assessed at time of ultrasound and blood draw (single day appointment, 1 hour)
reproductive history	A secondary aim is to characterize the reproductive histories of women who have completed a course of endocrine therapy for the prevention or treatment of breast cancer.	assessed at time of reproductive history survey (30 minutes long, one-time assessment)
lifestyle factors, medical history, and demographics	A secondary aim is to correlate biomarkers of ovarian age and age of menopause onset with lifestyle factors, medical history, and demographics in pre- and postmenopausal women previously treated with endocrine therapy, accounting for age and ethnicity.	assessed at time of reproductive history survey (30 minutes long, one-time assessment)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Mitch Rosen, MD, UCSF Center for Reproductive Health

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 24, 2011
• First Submitted That Met QC Criteria: June 27, 2011
• First Posted (Estimate): June 29, 2011

Study Record Updates

• Last Update Posted (Estimate): March 9, 2015
• Last Update Submitted That Met QC Criteria: March 6, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: breast cancer; hormone therapy; fertility; ovarian reserve; ovarian aging
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 025950