What is a BARD1 gene mutation? What you should know

What is an inherited BARD1 mutation? General information for carriers

• The name BARD1 comes from "BRCA1 Associated Ring Domain 1". The gene called BARD1 is located on chromosome 2 and, to repair damaged DNA, works with BRCA1. Although these two genes work together, the effects of their mutations differ; people who carry a BARD1 mutation do not have the same cancer risk as people who carry a BRCA1 mutation.
• Inherited BARD1 mutation carriers who are women have an increased risk of breast cancer. Studies examining whether an inherited BARD1 mutation increases the risk of other cancers have been inconsistent.
• There is still insufficient evidence on how best to manage cancer risk in people who carry a BARD1 mutation.
• People who carry a BARD1 mutation and have been diagnosed with cancer may receive PARP inhibitors as specific treatments or participate in clinical trials.
• Both men and women can carry a mutation in the BARD1 gene.

Which cancer risks does an inherited BARD1 mutation increase?

If your BARD1 mutation test is positive, it is recommended that you seek help in reviewing your personal and family cancer history and choosing the best plan to manage your cancer risk from a multidisciplinary oncology team through a consultation.

• For women who carry a BARD1 mutation, triple-negative breast cancer is included in their increased breast cancer risk.
• There is still insufficient evidence to show definitively that a BARD1 mutation is associated with an increased risk of other cancer types.

Studies on cancer risk in people who carry a BARD1 mutation are ongoing.

Risk management for people with an inherited BARD1 mutation

The United States National Comprehensive Cancer Network (NCCN) provides risk-management guidelines for people with BARD1 mutations. You are advised to consult a multidisciplinary oncology team that can review your personal and family cancer history and help you decide on the best risk-management plan.

Breast cancer screening and prevention

Experts recommend that women with a BARD1 mutation undergo screening in their early 40s or earlier if there is a family history of breast cancer.

• Every year, where appropriate, 3-dimensional mammograms as part of mammogram screenings
• Annual contrast-enhanced breast magnetic resonance imaging (MR)

Screening and prevention of other cancers

There are insufficient studies showing a benefit from screening and prevention for other cancers in people who carry a BARD1 mutation. Experts therefore recommend managing these risks based on the family history of cancer. People with a BARD1 mutation may participate in research studies on cancer screening and prevention.

Cancer treatment for people with an inherited BARD1 mutation

People with an inherited BARD1 mutation who have been diagnosed with cancer may have different treatment options from people who do not carry a mutation. You may also enroll in a clinical trial studying the best treatment for people with an inherited BARD1 mutation.

If you have an inherited BARD1 mutation, have been diagnosed with cancer and any of the following apply to you, you may wish to discuss your medical options with your doctor.

• Having metastatic prostate cancer.
• Having advanced ovarian cancer.

PARP inhibitors

PARP inhibitors are a type of targeted therapy that works by blocking a protein used to repair damaged DNA. They were initially developed to treat cancer in people carrying an inherited BRCA1 or BRCA2 mutation. Since then, research and additional FDA approvals have expanded the use of PARP inhibitors to more situations. People with a BARD1 mutation who have been diagnosed with cancer may wish to ask their doctors about PARP inhibitor treatment.

PARP inhibitors for metastatic prostate cancer

The PARP inhibitor Lynparza (olaparib) has received FDA approval to treat men with metastatic castration-resistant prostate cancer who have a mutation in BARD1 or another gene involved in a certain type of DNA damage repair. Lynparza is approved following enzalutamide (Xtandi) or abiraterone (Zytiga) in men whose prostate cancer has progressed on these treatments.

PARP inhibitors for advanced ovarian, fallopian tube or primary peritoneal cancer

Various PARP inhibitors have been approved to treat ovarian cancer at different stages of the disease. In some situations, HRD (homologous recombination deficiency) testing is a tumor biomarker test that may help women who carry a BARD1 mutation and have advanced ovarian cancer learn whether they might benefit from a PARP inhibitor.

Advanced cancer recurring after third-line treatment:

• HRD testing can help women with advanced ovarian cancer that has recurred after third-line treatment and an inherited BARD1 mutation determine whether the PARP inhibitor Zejula (niraparib) may benefit them.

Maintenance treatment after first-line therapy:

• HRD testing helps women with advanced ovarian cancer and an inherited BARD1 mutation determine whether, as maintenance treatment after first-line platinum chemotherapy, Avastin (bevacizumab) in combination with the PARP inhibitor Lynparza (olaparib) may benefit them.
• Zejula has been approved for maintenance treatment in women with advanced ovarian, fallopian tube or primary peritoneal cancer who have had a complete or partial response to first-line platinum-based chemotherapy. Zejula does not require HRD testing for maintenance treatment.

Maintenance treatment after treatment of recurrent cancer:

• Zejula, Rubraca (rucaparib) and Lynparza have all been approved for maintenance treatment in women with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who have had a complete or partial response to platinum-based chemotherapy.