Genetic Markers of Susceptibility to Chemotherapy-induced Ovarian Damage in Cancer Patients Undergoing Ovarian Biopsy for Cryopreservation.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Breast Cancer, Hodgkin Lymphoma. Basic parameters: 18 years — 38 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Italian Cancer Registry data show a steady increase in the number of cancer survivors due to advances in treatment. However, these treatments can impair ovarian function, causing premature ovarian insufficiency (POI). Women with POI may experience vasomotor symptoms, infertility, psychological distress, and a significant reduction in quality of life. POI typically occurs before age 40 and is characterized by irregular menstruation and biochemical alterations (elevated gonadotropins and low estradiol). Chronic estrogen deficiency in POI is associated with increased risks of cardiovascular disease, cognitive decline, osteoporosis, psychological issues, and reproductive dysfunction. Preliminary studies suggest that chemotherapy-induced POI results from genetic changes in ovarian tissue, indicating a crucial role of genetic variations in individual susceptibility. Incidence rates of POI vary widely: about 38% after Hodgkin lymphoma and between 15% and 94% after breast cancer. Currently, there is no personalized pre-treatment risk assessment, complicating informed decision-making regarding ovarian function and fertility. Fertility preservation options include ovarian tissue and oocyte cryopreservation. This study aims to compare the mutational status of DNA repair genes in ovarian tissue fragments from women who underwent ovarian cryopreservation and completed chemotherapy for lymphoma or breast cancer, categorized into those who developed POI and those who did not. Additionally, the mutational load of these genes will be compared between groups. The study includes patients aged 18-38 who preserved ovarian tissue before gonadotoxic therapy between 2002 and 2024 at the IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di S. Orsola. Two groups will be analyzed: Group 1: Patients who developed POI after gonadotoxic treatment Group 2: Patients who did not develop POI Group assignment will be based on clinical and anamnesis data. Cryopreserved ovarian tissue from all participants will undergo advanced molecular analyses by Next Generation Sequencing (NGS) to assess germline and somatic mutational status and load. The genetic variant analysis, conducted in collaboration with the Computational Genomics Unit of IRCCS AOUBO, will focus on a panel of 26 DNA repair genes. Bioinformatic analysis will be performed using the Ion Reporter platform, with clinically relevant variants validated by orthogonal methods. The study plans to enroll approximately 50 patients, 25 per group.
Primary outcome measures
- To compare the mutational status of genes involved in DNA repair mechanisms in ovarian tissue fragments from women who underwent ovarian cryopreservation and completed chemotherapy treatment for lymphoma or breast cancer [Time frame: At least 6 months after the end of chemotherapy]
Secondary outcome measures (1)
- To compare the mutational load of altered genes between women who developed POI and those who did not after undergoing chemotherapy [Time frame: At least 6 months after the end of chemotherapy]
Eligibility criteria
Inclusion criteria
- Age ≥ 18 and ≤ 38 years at the time of cryopreservation
- Patient diagnosed with breast cancer or lymphoma, who underwent ovarian biopsy and cryopreservation of ovarian tissue prior to the initiation of gonadotoxic treatment
- Gonadotoxic therapy completed at least 6 months prior
- Written informed consent obtained for participation in the study and for the processing of personal, sensitive, and genetic data
Exclusion criteria
- Patients with a history of gonadotoxic treatments prior to ovarian tissue cryopreservation
- Patients undergoing hormonal therapy that suppresses ovarian function (e.g., GnRH analogs)
- Presence of other conditions potentially responsible for premature ovarian insufficiency \[e.g., BRCA1 and BRCA2 mutations, Li-Fraumeni syndrome, Bloom syndrome, Fanconi anemia, Fragile X syndrome, Cowden syndrome, Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer - HNPCC), Ataxia-Telangiectasia\]
- Family history of premature ovarian insufficiency
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Case-control
Study locations
Italy · 1 center
- IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna
Identifiers
NCT: NCT07270679 · GTM_OCP · FERR24RD