Evaluation of Individual Sensitivity to the Gonadotoxicity of Chemotherapy in Young Patients With Breast Cancer

NCT03731845 | Active Not Recruiting

• 2 other identifiers: K160913J2017-A02111-52
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

Over the past decade, advances in diagnosis and treatments have dramatically increased the rates of cure for young patients with cancer. As a consequence, a new population of cancer survivors has emerged whose fertility is compromised after cancer therapy. Indeed, gonadotoxicity is a well-known long-term side effect of cancer treatment in young patients having survived malignant diseases. More than 80% of women of childbearing age, treated for breast cancer with standard protocol of neoadjuvant (4 cycles of 5-fluorouracile - epirubicin- cyclophosphamide (FEC) and 4 cycles of docetaxel) or adjuvant chemotherapy (3 FEC and 3 docetaxel), show an alteration of their ovarian reserve 2 years after completion of the treatment, as a result of chemotherapy-related follicular loss. Therefore, according to the extent of the follicular damages, the gonadal function may vary from moderate to severe diminished ovarian reserve (DOR) and possibly to the ultimate stage of premature ovarian insufficiency (POI). Investigators propose a multicentric and prospective study of a cohort of young women with breast cancer to evaluate whether genetic polymorphisms, previously identified as being correlated with age at menopause in the healthy population, are associated with the intensity of the follicular decline following chemotherapy in young breast cancer survivors.

Conditions

Breast Cancer

Keywords

Breast Cancer; ovarian reserve; primary ovarian insufficiency; chemotherapy; single nucleotide polymorphism

Outcome Measures

Primary Outcomes (1)

• Assessment of ovarian reserve

  is an aggregated measure of FSH, AMH serum level, Antral Follicle Count and menstrual profile : * Normal ovarian reserve: persistence of menstrual cycle, FSH\<40 IU/L and AMH\>1.1 ng/mL or AFC\>7 follicles * Moderate diminished ovarian reserve : persistence of menstrual cycle, FSH\<40 IU/L and 0.5≤AMH≤1.1 ng/mL or 5≤AFC≤7 follicles * Severe diminished ovarian reserve : persistence of menstrual cycle and AMH\<0.5 ng/mL or AFC\<5 follicles * Premature ovarian insufficiency is defined by amenorrhea above four months and FSH level ≥40 IU/L in women before 40 years. AMH serum levels and ultrasonographic evaluation of AFC will be evaluated FIVEyears after the end of chemotherapy.

  5 years after completion of chemotherapy

Secondary Outcomes (5)

• Menstrual profile: amenorrhea, spaniomenorrhea, normal cycle length (28-35 days)

  5 years

• Pregnancy rates

  5 years

• AMH level

  6, 12, 24, 36, 48, 60 months following the end of chemotherapy.

• Antral Follicle Count (Ultrasound evaluation)

  6, 12, 24, 36, 48, 60 months following the end of chemotherapy.

• Follicular decline (definition below)

  2 years after the completion of chemotherapy

Study Arms (1)

patient

EXPERIMENTAL

Genetic: Blood sample for genetic test; Biological: Blood sample for hormonal measurement; Other: Ovarian ultrasound scan

Interventions

Blood sample for genetic test GENETIC

Patients will be genotyped for single nucleotide polymorphism previously found to be associated with age at natural menopause

patient

Blood sample for hormonal measurement BIOLOGICAL

at each visit : 2x7ml. At the end of the study hormonal measurements (AMH, P4, LH, FSH, E25)

patient

Ovarian ultrasound scan OTHER

Ovarian ultrasound scan at follow up visits (Y1,Y1.5, Y2.5 Y3.5 Y4.5 Y5.5)

patient

Eligibility Criteria

• Age: 18 Years - 36 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18 - 36 years
• Diagnosis of breast cancer
• BMI≤30 Kg/m2
• Baseline antral Follicular count (before initiation of chemotherapy): 10-40 follicles measuring 2 - 9 mm in diameter
• Regular and ovulatory menstrual cycles
• Indication of neoadjuvant (4 FEC and 4 docetaxel) or adjuvant (3 FEC and 3 docetaxel) chemotherapy
• Free informed and written consent, dated and signed by the patient and the investigator
• Patient affiliated to the French National Social Security System
• Previous history of chemotherapy
• History of ovarian surgery or endometrioma
• Ovarian Polycystic Syndrome
• DOR or POI before chemotherapy
• Virgin patients

You may not qualify if:

• \- Intensification of chemotherapy

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Antoine Béclère Hospital

Clamart, 92140, France

Location

MeSH Terms

Conditions

Breast Neoplasms; Primary Ovarian Insufficiency

Interventions

Blood Specimen Collection; Genetic Testing

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Charlotte SONIGO, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Michael Grynberg, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: November 6, 2018
• Study Start: April 1, 2019
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: November 20, 2025

Record last verified: 2025-09

Locations

FR (1)