Impact of Breast Cancer on Human Folliculogenesis

NCT ID: NCT07148141

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-11
• Study Completion Date: 2027-08-31

Brief Summary

Advances in cancer diagnosis and treatments have improved the 5-year survival rate for patients over the last decade. Nevertheless, cancer treatments frequently alter patient's fertility, thus compromising their ability to conceive a child after remission. Consequently, it is recommended to propose fertility preservation to patients before cancer therapy. The reference technique for preserving women's fertility the vitrification of mature oocytes after hormonal stimulation. In the context of cancer, different studies have shown that ovarian response to stimulation seems to be altered compared to healthy context, with a reduced number of mature oocytes collected, and altered oocyte quality, thus reducing the number of oocytes capable of producing a viable embryo. Hence, cancer seems to exert a deleterious impact on women's fertility. Nevertheless, the mechanisms by which the cancer may impair the ovarian functions are poorly understood. This innovative project aims to study the impact of breast cancer itself (the most frequent cancer in reproductive-aged women) on ovarian functions, and more precisely on the cholesterol biosynthesis pathway. Indeed, cholesterol homeostasis is essential for oocyte maturation and fertilization. The objectives of this study are i) to evaluate the impact of breast cancer on ovarian reserve and response to hormonal stimulation according to the molecular subtypes of breast cancer and ii) to evaluate the impact of breast cancer on ovarian cholesterol homeostasis in granulosa cells and follicular fluids.

This original approach will improve the understanding of the mechanisms underlying the impact of breast cancer on ovarian functions, and will have a strong clinical impact by helping to optimize fertility preservation strategies based on tumour molecular subtypes.

Detailed Description

Breast cancer patients (stratified into three molecular subgroups based on tumour hormonal status: HR+, HER2+, or triple-negative (TN)) and healthy oocyte donors (OD) are included in this study. During oocyte retrieval (for fertility preservation or oocyte donation), cumulus-oocyte complexes (COCs) are collected following ovarian stimulation. COCs are treated with hyaluronidase to separate the oocytes from surrounding cumulus granulosa cells. Clinical data regarding ovarian reserve and response to stimulation are collected.

Comparative analyses are conducted between breast cancer patients and oocyte donors, as well as between each molecular subgroup (TN vs. OD, HR+ vs. OD, HER2+ vs. OD). Following retrieval, granulosa cells and follicular fluids are collected. Total RNA is extracted from cumulus cells for RT-qPCR quantification of key enzymes and regulators involved in the cholesterol biosynthesis pathway. In parallel, cholesterol levels in follicular fluid are quantified using GC-MS/MS or FID-MS/MS.

This extended protocol enables both clinical and molecular comparisons to assess how breast cancer subtypes may differentially impact ovarian response and follicular environment

Conditions

Breast Cancer Female; Infertility, Female

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Breast cancer patients (BC)

Breast cancer subgroups (Triple-negative breast cancer (TN), Hormone-dependent breast cancer (HR+), HER2-amplified breast cancer (HER2+))

Ovarian stimulation

Intervention Type: OTHER

Ovarian stimulation before oocytes retrieval

Oocyte donors (OD)

Healthy women

Ovarian stimulation

Intervention Type: OTHER

Ovarian stimulation before oocytes retrieval

Interventions

Ovarian stimulation

Ovarian stimulation before oocytes retrieval

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Women above 18 years old and below 38 years old
• First hormonal stimulation cycle
• No dysovulation
• No cancer treatments prior fertility preservation (tumour resection, chemotherapy, radiotherapy)
• Women capable of giving written informed consent to participate in the research study
• Affiliated to social welfare service

Exclusion Criteria

• Women below 18 years old and above 38 years old
• Endocrine disease
• Endometriosis
• Any cancer treatments prior fertility preservation (tumour resection, chemotherapy, radiotherapy)
• Previous hormonal stimulation cycle of less than six months

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 38 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Florence Brugnon, MD, PhD, HDR

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Clermont-Ferrand

Locations

CHU Clermont-Ferrand

Clermont-Ferrand, Auvergne Rhones-Alpes, France

Countries

France

Other Identifiers

2019_BRUGNON_FERTICAN

Identifier Type: -

Identifier Source: org_study_id