Investigating the Impact of Tamoxifen Therapy on Ovarian Aging

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01384526
First received: June 24, 2011
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

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.


Condition
Breast Cancer
Fertility

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Investigating the Impact of Tamoxifen Therapy on Ovarian Aging

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • age of menopause onset [ Time Frame: assessed at time of reproductive history survey (30 minutes long, one-time assessment) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • biomarkers of ovarian reserve [ Time Frame: assessed at time of ultrasound and blood draw (single day appointment, 1 hour) ] [ Designated as safety issue: No ]
    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.

  • reproductive history [ Time Frame: assessed at time of reproductive history survey (30 minutes long, one-time assessment) ] [ Designated as safety issue: No ]
    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.

  • lifestyle factors, medical history, and demographics [ Time Frame: assessed at time of reproductive history survey (30 minutes long, one-time assessment) ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

Serum AMH, FSH, estradiol, and Inhibin B will be measured. Blood will be collected and processed by the UCSF Center for Reproductive Health. Serum samples will be stored at -80oC in a designated freezer with an alarm system. Biomarker assessments will be performed by Quest Laboratories under standard quality control.


Estimated Enrollment: 200
Study Start Date: June 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
history of hormone therapy
no history of hormone therapy

  Eligibility

Ages Eligible for Study:   25 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01384526

Contacts
Contact: A. Jo Chien, MD 415-885-7577 jo.chien@ucsf.edu
Contact: Mitch Rosen, MD 415-885-7870 RosenM@obgyn.ucsf.edu

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: A. Jo Chien, MD    415-885-7577    jo.chien@ucsf.edu   
Principal Investigator: A. Jo Chien, MD         
Principal Investigator: Mitch Rosen, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: A. Jo Chien, MD University of California, San Francisco
Principal Investigator: Mitch Rosen, MD UCSF Center for Reproductive Health
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01384526     History of Changes
Other Study ID Numbers: 025950
Study First Received: June 24, 2011
Last Updated: August 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
hormone therapy
ovarian aging
ovarian reserve
fertility
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 27, 2014