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.

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

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.