Pregnancy Outcomes After Breast Cancer in Young Women With Germline Pathogenic Variants in Genes Other Than BRCA

This retrospective, multicenter, observational study aims to evaluate the prognostic impact of pregnancy after breast cancer diagnosis in young women harboring germline pathogenic variants in breast cancer susceptibility genes other than BRCA1/2, including TP53, PALB2, PTEN, CDH1, STK11, CHEK2, ATM, BARD1, RAD51C, and RAD51D.

Although pregnancy after breast cancer has been shown to be safe in the overall population of young breast cancer survivors and in carriers of BRCA1/2 pathogenic variants, evidence remains limited for patients with pathogenic variants in other breast cancer susceptibility genes. This knowledge gap represents a relevant unmet need in oncofertility counseling and survivorship care.

The study will include patients diagnosed with stage I-III invasive breast cancer at age 40 years or younger between January 2000 and December 2025. The primary objectives are to assess the prognostic impact of pregnancy after breast cancer diagnosis and to evaluate the cumulative incidence of pregnancy in this population. Secondary objectives include the assessment of pregnancy, fetal, and obstetrical outcomes, the safety of assisted reproductive technology procedures, patterns of care including risk-reducing surgeries, survival outcomes according to clinicopathologic and genetic subgroups, and the occurrence of second primary malignancies.

Data will be collected retrospectively from participating centers within the Beyond BRCA BCY Collaboration.

Inclusion criteria

• Diagnosis of stage I-III invasive breast cancer between January 2000 and December 2025
• Age at breast cancer diagnosis ≤40 years
• Germline pathogenic variant in at least one of the following breast cancer susceptibility genes other than BRCA: TP53, PALB2, PTEN, CDH1, STK11, CHEK2, ATM, BARD1, RAD51C, or RAD51D

Exclusion criteria

• Known germline pathogenic variant in breast cancer susceptibility genes without a diagnosis of invasive breast cancer
• Diagnosis of ovarian cancer or other malignancies without a prior history of invasive breast cancer
• Diagnosis of invasive breast cancer with germline variants of uncertain significance in breast cancer susceptibility genes
• De novo stage IV breast cancer