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

Retrospective Observational Study on the Prognostic Impact of Pregnancy in Young Women With Breast Cancer Harboring a Germline Pathogenic Variant in Breast Cancer-related Genes Other Than BRCA1/2: the "Beyond BRCA BCY Collaboration"

The present study aims to refine the understanding of the prognostic impact of pregnancy after breast cancer in young women harboring germline pathogenic variants in breast cancer susceptibility genes other than BRCA

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Breast Cancer and Pregnancy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 2200

Contacts and Locations

• Study Contact: Name: Eva Blondeaux, MD; Phone Number: +39 010 555 8502; Email: BCYcollaboration@aomliguria.it
• Study Contact Backup: Name: Luca Arecco, MD; Email: BCYcollaboration@aomliguria.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Young women diagnosed at age 40 years or younger with stage I-III invasive breast cancer between January 2000 and December 2025 and harboring a germline pathogenic variant in a breast cancer susceptibility gene other than BRCA1/2, including TP53, PALB2, PTEN, CDH1, STK11, CHEK2, ATM, BARD1, RAD51C, and RAD51D.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pregnant cohort; Women with one or more pregnancies any time after breast cancer diagnosis
Non-pregnant cohort; Women with no subsequent pregnancies after breast cancer diagnosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative Incidence of Pregnancy After Breast Cancer Diagnosis	Up to 20 years from breast cancer diagnosis
Invasive Disease-Free Survival (iDFS)	Up to 20 years from breast cancer diagnosis

Collaborators and Investigators

• Sponsor: Jules Bordet Institute
• Investigators: Principal Investigator: Matteo Lambertini, MD, PhD, IRCCS Azienda Ospedaliera Metropolitana; Principal Investigator: Evandro de Azambuja, MD, PhD, Jules Bordet Institute

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 24, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; Pregnancy; TP53; PALB2; PTEN; STK11; Oncofertility; ATM; RAD51C; RAD51D; BARD1; Young Women; CHEK2; CDH1; Hereditary Breast Cancer; Germline Pathogenic Variants; Breast Cancer Susceptibility Genes
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Breast Cancer, Familial
• Other Study ID Numbers: IJB-BEYOND-BCY-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified individual participant data may be shared upon reasonable request, subject to submission of a formal research proposal to the study Principal Investigators and review and approval by the study leadership. Any data sharing will be subject to applicable ethics approvals, data transfer agreements, local institutional requirements, and data protection regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No