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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00823654
• Other study ID #: 08-156
• Status: Recruiting
• Start date: January 2009
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Shari Goldfarb, MD
• Phone: 646-888-5080
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 609
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 44 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Other:
• Blood draw and questionnaires
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
• Blood draw and questionnaires
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

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Presbyterian Hospital-Weill Medical College of Cornell University	New York	New York
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (4)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	New York Presbyterian Hospital, Weill Medical College of Cornell University, Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	To study the differences in ovarian reserve between BRCA1+ and BRCA2+ women.		2 years
Secondary	To study sexual health and function in unaffected high risk BRCA mutation carriers		2 years

External Links

•   Memorial Sloan Kettering Cancer Center