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

February 1, 2024 updated by: Memorial Sloan Kettering Cancer Center

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

The purpose of this study is to see how the cancer treatment affects the ovaries. Cancer treatment can make it hard for a person to conceive a child in the future. It may also bring on early menopause. We will check blood levels of hormones that the ovaries produce. We will do this before, during, and after the cancer treatment. We will also ask the patient to fill out questionnaires about their menstrual cycle (periods) and information about your health and pregnancies. This may help us learn which women will be more likely to have early menopause.

Study Overview

Study Type

Observational

Enrollment (Estimated)

609

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Shari Goldfarb, MD
  • Phone Number: 646-888-5080

Study Contact Backup

  • Name: Kimberly Van Zee, MD
  • Phone Number: 646-888-5362

Study Locations

    • New Jersey
      • Basking Ridge, New Jersey, United States
        • Recruiting
        • Memorial Sloan Kettering Basking Ridge
        • Contact:
          • Shari Goldfarb, MD
          • Phone Number: 646-888-5080
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth
        • Contact:
          • Shari Goldfarb, MD
          • Phone Number: 646-888-5080
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen
        • Contact:
          • Shari Goldfarb, MD
          • Phone Number: 646-888-5080
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Commack
        • Contact:
          • Shari Goldfarb, MD
          • Phone Number: 646-888-5080
      • Harrison, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester
        • Contact:
          • Shari Goldfarb, MD
          • Phone Number: 646-888-5080
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Shari Goldfarb, MD
          • Phone Number: 646-888-5080
        • Contact:
          • Kimberly Van Zee, MD
          • Phone Number: 646-888-5362
        • Principal Investigator:
          • Shari Goldfarb, MD
      • New York, New York, United States, 10065
        • Active, not recruiting
        • New York Presbyterian Hospital-Weill Medical College of Cornell University
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau
        • Contact:
          • Shari Goldfarb, MD
          • Phone Number: 646-888-5080

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 44 years (Adult)

Accepts Healthy Volunteers

Yes

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.

Description

Inclusion Criteria:

For Premenopausal Women with Early Stage Breast Cancer

  • Premenopausal female patients age 18-44 with breast cancer as defined as:

    a. 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. If chemotherapy is planned, the regimen must be either CMF, anthracycline containing, or taxane containing. If hormonal therapy is planned, the regimen must be limited to tamoxifen. All biologics (e.g. bevacizumab, trastuzumab, lapatinib, etc.) are allowed in addition to the above therapies.

  • Have regular menstrual cycles; 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.

Subject Inclusion:

For Unaffected High Risk Premenopausal Women with BRCA mutations

  • Premenopausal Women ages 25-45 with known BRCA mutations
  • Have regular menstrual (21-35 days); 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.
  • No history of breast or ovary cancer.

Subject Inclusion:

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
  • No prior ovarian surgery or ovarian disease
  • No prior chemotherapy
  • Regular menstrual periods (21-35 days), no PCOS
  • No hormonal contraception within the prior 4 weeks
  • 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 doxo/Adriamycin) and Cy (AC)-based chemotherapy protocol

Exclusion Criteria:

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.

Subject Exclusion Criteria:

For Unaffected High Risk Premenopausal Women with BRCA mutation

  • Prior chemotherapy or immunotherapy for breast cancer or any other cancer
  • Ovarian resection, unilateral or bilateral oophorectomy, hysterectomy or radiation to pelvic region or ovarian disease (e.g. polycystic ovarian syndrome).
  • Plans for risk-reducing bilateral oophorectomy within one year
  • Prior known infertility; (except women who have undergone voluntary tubal ligation); 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 Subject Exclusion Criteria 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.
  • Women aged >42 years will be excluded as they carry a very high probability of chemotherapy-induced OI49. It is important to select an age range where immediate OI is less likely to occur because if most women become menopausal post-chemotherapy, the comparison of ovarian reserve decline will not be feasible.
  • In our prior grant period, we showed that the AC-based and CMF regimens similarly compromise ovarian reserve (Fig. 1)9 Currently, the AC-based chemotherapy is utilized in >90% breast ca cases, and CMF protocol is rarely administered9. For this reason and to enhance uniformity, rare non-AC-based protocols will be excluded.
  • A previous study showed that smoking and BRCA mutations may have additive negative effects on the age of menopause27, consequently, we will exclude current smokers (smoked 100 cigarettes lifetime and currently smokes, per CDC). Based on our past studies6,9, the smoking incidence is low in our study population (<20%) and should not significantly limit accrual.
  • BMI: In our recent publication9 (Fig. 1), the mean BMI was 24.22 ±0.4 (median 23.2; range 17-42); hence the extreme BMI values are rare in our population. Nevertheless, those with BMI of <18.5 and >40 will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Premenopausal Women with Early Stage Breast Cancer

At the start of the study: blood draw, questionnaire and menstrual calendar ↓ Start planned therapy (or observation/surveillance) for cancer treatment

Tests in the middle of chemotherapy (if applicable):

Blood draw and collection of monthly menstrual calendars ↓

Tests when chemotherapy is over (if applicable):

Blood draw and collection of monthly menstrual calendars

Tests every 4 months for about 1 year:

Blood draw, collection of monthly menstrual calendars, and questionnaire ↓

Tests every 6 months for about 1 year:

Blood draw, collection of monthly menstrual calendars, and questionnaire

Yearly follow-up for about 2 years:

Blood draw collection of monthly menstrual calendars, and questionnaire

Study Schema for Unaffected High Risk Women with BRCA mutations Identify eligible premenopausal patients and obtain informed consent

↓ Register patients at Memorial Sloan-Kettering Cancer Center

↓ Baseline evaluation: Blood draw and baseline reproductive health and sexual questionnaires (Appendix A)/menstrual calendar (Appendix C)

↓ Annual follow-up x 4 years Blood draw and collection of monthly menstrual calendars/follow-up reproductive health and sexual health questionnaires

↓ Year 1 follow up Blood draw and collection of monthly menstrual calendars /follow-up reproductive and sexual health questionnaires

↓ Optional annual follow-up years 2-5 Blood draw and collection of monthly menstrual calendars /follow-up reproductive and sexual health questionnaires

Unaffected High Risk Women with BRCA mutations

At the start of the study: blood draw, questionnaire and menstrual calendar ↓ Start planned therapy (or observation/surveillance) for cancer treatment

Tests in the middle of chemotherapy (if applicable):

Blood draw and collection of monthly menstrual calendars ↓

Tests when chemotherapy is over (if applicable):

Blood draw and collection of monthly menstrual calendars

Tests every 4 months for about 1 year:

Blood draw, collection of monthly menstrual calendars, and questionnaire ↓

Tests every 6 months for about 1 year:

Blood draw, collection of monthly menstrual calendars, and questionnaire

Yearly follow-up for about 2 years:

Blood draw collection of monthly menstrual calendars, and questionnaire

Study Schema for Unaffected High Risk Women with BRCA mutations Identify eligible premenopausal patients and obtain informed consent

↓ Register patients at Memorial Sloan-Kettering Cancer Center

↓ Baseline evaluation: Blood draw and baseline reproductive health and sexual questionnaires (Appendix A)/menstrual calendar (Appendix C)

↓ Annual follow-up x 4 years Blood draw and collection of monthly menstrual calendars/follow-up reproductive health and sexual health questionnaires

↓ Year 1 follow up Blood draw and collection of monthly menstrual calendars /follow-up reproductive and sexual health questionnaires

↓ Optional annual follow-up years 2-5 Blood draw and collection of monthly menstrual calendars /follow-up reproductive and sexual health questionnaires

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
characterize the changes in serum AMH from baseline to 1 year post-chemo (or 1 year into hormonal therapy if no chemotherapy planned)
Time Frame: 2 years
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 Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 2 years
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.
Time Frame: 2 years
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.
Time Frame: 2 years
2 years
To study the differences in ovarian reserve between BRCA1+ and BRCA2+ women.
Time Frame: 2 years
2 years
To study sexual health and function in unaffected high risk BRCA mutation carriers
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Shari Goldfarb, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2009

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

January 14, 2009

First Submitted That Met QC Criteria

January 14, 2009

First Posted (Estimated)

January 15, 2009

Study Record Updates

Last Update Posted (Estimated)

February 2, 2024

Last Update Submitted That Met QC Criteria

February 1, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • 08-156

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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