Serum Biomarkers to Characterize the Effects of Therapy on Ovarian Reserve in Premenopausal Women With Early-stage Breast Cancer or BRCA Mutations

NCT00823654 | Recruiting

• 1 other identifier: 08-156
• Study Type: observational
• Target: 609
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to learn more about the effects of your BRCA mutation on the ovaries. The BRCA gene can make it hard to conceive a child in the future. It may also bring on early menopause. The researchers will check blood levels of hormones that the ovaries produce. The hormones that researchers will check are anti-Mullerian hormone (AMH), estradiol and follicle stimulating hormone (FSH). The researchers will do this before, during, and after cancer treatment. The researchers will also ask you to fill out questionnaires about your menstrual cycle (your periods) and information about your health and pregnancies. This may help us learn which women will be more likely to have early menopause.

Conditions

Breast Cancer

Keywords

Breast; Questionaires; Blood draw; BRCA1; BRCA2; 08-156

Outcome Measures

Primary Outcomes (1)

• characterize the changes in serum AMH from baseline to 1 year post-chemo (or 1 year into hormonal therapy if no chemotherapy planned)

  in premenopausal breast cancer patients \& to characterize the changes in serum AMH from baseline to 1 year in unaffected high risk BRCA mutation carriers.

  2 years

Secondary Outcomes (5)

• To characterize the changes in serum estradiol and FSH from baseline to one year postchemotherapy (or 1 year into hormonal therapy if no chemotherapy planned) in premenopausal breast cancer patients and BRCA mutation carriers.

  2 years

• To characterize the changes over time in serum AMH, estradiol, and FSH in premenopausal breast cancer patients and unaffected high risk BRCA mutation carriers.

  2 years

• To describe the impact of commonly used therapies for early-stage breast cancer on self-reported monthly menstrual cycles and future pregnancy/reproductive health.

  2 years

• To study the differences in ovarian reserve between BRCA1+ and BRCA2+ women.

  2 years

• To study sexual health and function in unaffected high risk BRCA mutation carriers

  2 years

Study Arms (2)

Premenopausal Women with Early Stage Breast Cancer

Other: Blood draw and questionnaires

Unaffected High Risk Women with BRCA mutations

Other: Blood draw and questionnaires

Interventions

Blood draw and questionnaires OTHER

Identify eligible premenopausal patients and obtain informed consent ↓ Register patients at Memorial Sloan Kettering Cancer Center ↓ Baseline evaluation: Blood draw and baseline reproductive health questionnaire (Appendix A)/menstrual calendar (Appendix C) / sexual health questionnaires (Appendices E, F, G) ↓ Start planned therapy (or observation) ↓ Evaluation at completion of chemotherapy Blood draw and collection of monthly menstrual calendars ↓ One year post chemo Blood draw and collection of monthly menstrual calendars/follow-up reproductive health questionnaire (Appendix B) ↓ Annual follow-up x 3 years Blood draw and collection of monthly menstrual calendars/follow-up reproductive health questionnaire (Appendix B) )/ sexual health questionnaires (Appendices E, F, G)

Premenopausal Women with Early Stage Breast Cancer

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients of premenopausal women with early-stage breast cancer will be recruited from the Breast Cancer Service at MSKCC and New York Presbyterian Hospital-Weill Medical College of Cornell University. In addition, breast cancer patients seeking consultation with a reproductive endocrinologist to address issues of fertility preservation prior to the start of therapy will be offered participation (Dr. Oktay at Yale Medicine. Patients of unaffected high risk premenopausal women with BRCA mutations will be recruited from the Breast Cancer Services especially the high risk surveillance clinics at MSKCC and New York Presbyterian Hospital-Weill Medical College of Cornell Univeristy.

You may qualify if:

• For Premenopausal Women with Early Stage Breast Cancer
• Participant is between 18-44 years old.
• Participant is premenopausal.
• Participant is female.
• Participant has a known breast cancer diagnosis of AJCC Stage 0-III breast cancer, regardless of hormone-receptor status or HER2-overexpression, before the start of planned adjuvant or neoadjuvant chemotherapy and/or hormonal therapy.
• The chemotherapy regimen must be either CMF, anthracycline-containing, or taxane-containing. If hormonal therapy is planned, the regimen must be limited to tamoxifen All biologics are allowed in addition to the above therapies.
• The participant has regular menstrual cycles; note: patients can have no more than 1 irregular cycle (too early or too late) within the past year and/or at least 10 spontaneous cycles within the past year. Exceptions are made for patients who have been pregnant in the last 12 months and patients with IUDs or a LARC.
• For Unaffected High Risk Premenopausal Women with BRCA mutations
• The participant is between 25 and 45 years of age.
• The participant is female.
• The patient has a known BRCA mutation.
• Have regular menstrual (21-35 days); patients can have no more than 1 irregular cycle (too early or too late) within the past year or were pregnant in the past 12 months, and/or at least 10 spontaneous cycles within the past year. Exceptions are made for patients who have been pregnant in the last 12 months and patients with IUDs or a LARC.
• For affected BRCA1 and BRCA2 mutation carriers, affected women with non-BRCA mutations, and BC patients with no mutations (control)
• Premenopausal women age 21-45 with stage 0-3 breast cancer. 2. No prior ovarian surgery or ovarian disease. 3. No prior chemotherapy. 4. Regular menstrual periods (21-35 days), no PCOS. 5. No hormonal contraception within the prior 4 weeks. 6. Mutation testing decision based on NCCN Guidelines V1.2021: according to these Guidelines, both centers test all pre-menopausal women with breast cancer for BRCA and non-BRCA mutations which are the subject of this proposal.
• \. Receiving an anthracycline (typically doxorubicin/Adriamycin) and Cy (AC)-based chemotherapy protocol.

You may not qualify if:

• For Cohort of Premenopausal Women with Early Stage Breast Cancer
• Prior therapy for breast cancer or any other cancer, such as chemotherapy, hormonal therapy or immunotherapy.
• Ovarian resection, unilateral or bilateral oophorectomy, hysterectomy or radiation to pelvic region.
• Plans for risk-reducing bilateral oophorectomy within one year of completion of chemotherapy.
• Prior known infertility; infertility is defined as one year of inability to conceive despite unprotected intercourse and/or the need to use medication (e.g clomiphene) or assisted reproductive technology (e.g. intrauterine insemination or in vitro fertilization) to attempt pregnancy.
• Family history of a first-degree relative with non-surgical menopause \< age 40
• Current pregnancy.
• For Unaffected High Risk Premenopausal Women with BRCA mutation
• Participant has therapy for breast cancer or any other cancer, such as chemotherapy, hormonal therapy or immunotherapy.
• Participant has ovarian resection, unilateral or bilateral oophorectomy, radiation to pelvic region.
• Participant has Plans for risk-reducing bilateral oophorectomy within one year of completion of chemotherapy.
• Participant has prior known infertility; infertility is defined as one year of inability to conceive despite unprotected intercourse and/or the need to use medication (e.g., clomiphene) or assisted reproductive technology (e.g., intrauterine insemination or in vitro fertilization) to attempt pregnancy.
• Participant has a family history of a first-degree relative with non-surgical menopause \< age 40.
• Participant is currently pregnant. For affected BRCA1 and BRCA2 mutation carriers, affected women with non-BRCA mutations, and BC patients with no mutations (control)
• \. Subjects who did not undergo mutation testing, as well as those who tested positive for more than one family (BRCA1, BRCA2, non-BRCA) of ATM-Pathway gene mutations, will be excluded.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Yale University: collaborator
• New York Presbyterian Hospital: collaborator
• Weill Medical College of Cornell University: collaborator

Study Sites (8)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

New York Presbyterian Hospital-Weill Medical College of Cornell University

New York, New York, 10065, United States

ACTIVE NOT RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Related Publications (1)

• Oktay KH, Bedoschi G, Goldfarb SB, Taylan E, Titus S, Palomaki GE, Cigler T, Robson M, Dickler MN. Increased chemotherapy-induced ovarian reserve loss in women with germline BRCA mutations due to oocyte deoxyribonucleic acid double strand break repair deficiency. Fertil Steril. 2020 Jun;113(6):1251-1260.e1. doi: 10.1016/j.fertnstert.2020.01.033. Epub 2020 Apr 22.

  PMID: 32331767 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Blood Specimen Collection; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Shari Goldfarb, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shari Goldfarb, MD

CONTACT

646-888-5080

Minna Lee, MD

CONTACT

646-888-6898

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2009
• First Posted: January 15, 2009
• Study Start: January 1, 2009
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 14, 2025

Record last verified: 2025-10

Locations

US (8)