First isolated in 2001, the BRIP1 (BRCA1 interaction protein C-terminal helicase 1) gene encodes for homologous recombination repair and facilitates DNA single- and double-strand break repair during DNA replication.
BRIP1 is a susceptibility biomarker that predicts a person’s potential for developing malignancy. Individuals who are homozygous for BRIP1 variation are at increased risk for developing Fanconi anemia, and heterozygotes may have an increased risk for developing several cancers, including ovarian, breast, and prostate.
The cumulative ovarian cancer risk associated with germline pathogenic variants in BRIP1 is 5%–15%, compared to 2% in the general population, according to the National Comprehensive Cancer Network’s Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic guidelines. Most patients are diagnosed after age 50, with a mean age of 63 at diagnosis. Ovarian cancer has few warning signs or effective screening strategies. Consideration can be given to risk-reducing bilateral salpingoophorectomy at age 45–50.
A patient’s risk for developing breast cancer with a pathogenic BRIP1 variant is not completely clear. An estimated 4% of breast cancer cases are associated with a pathogenic variant, and BRIP1 may be associated with an increased risk of triple-negative breast cancer. No specific recommendations currently exist for breast cancer screening and prevention in patients with pathogenic BRIP1 variants. Providers should make individual recommendations after carefully considering personal and family medical history and using a model such as the Breast Cancer Risk Assessment Tool or Tyrer-Cuzick Risk Assessment Calculator to determine risk. Depending on the magnitude of the risk, patients may consider beginning breast cancer screening at an earlier age, adding breast magnetic resonance imaging or ultrasound to screening, or using prevention strategies such as tamoxifen therapy or risk-reducing mastectomies.
Evidence from one study associated BRIP1 variants with a 5.6% increased risk for developing prostate cancer. Individuals with a pathogenic BRIP1 variant should engage in shared decision-making regarding recommendations for prostate screening, including age to start PSA testing, testing interval, and when to stop.
Individuals who are homozygous for BRIP1 variants may be at increased risk for developing Fanconi anemia. Fanconi anemia affects red blood cells, white blood cells, and platelets and is characterized by pancytopenia.
BRIP1 is also a prognostic biomarker that helps clinicians identify the likelihood of recurrence or progression. Pathogenic BRIP1 variants have been associated with earlier tumor recurrence and progression in breast and ovarian cancer, possibly because of an elevated cell proliferation rate.
BRIP1 is also a predictive biomarker that may indicate an individual’s response to certain cancer treatments. Pathogenic germline or somatic variants in genes that repair DNA damage are associated with the homologous recombination pathway and may respond to PARP inhibitor therapy. Somatic testing is recommended in patients with progressive or metastatic prostate cancer. If a germline or somatic BRIP1 pathogenic variant is found, patients may benefit from the PARP inhibitor olaparib.
The U.S. Food and Drug Administration has not currently approved any biomarker-directed targeted therapies for ovarian cancer. Clinical trials are ongoing with PARP inhibitors.
Oncology nurses can provide patient education about olaparib, including information on how to take the medication and its potential benefits and side effects. Printed patient education resources and follow-up to promote adherence and can support those discussions.
Multigene panels address overlaps in hereditary cancer syndrome presentations and more effectively identify individuals with actionable pathogenic variants than testing with a single-syndrome approach. However, they may identify pathogenic variants in genes such as BRIP1 for which formal management guidelines are limited. In those situations, recommendations for care are based not only on germline testing, but also an individual’s personal and family history. Oncology nurses can educate patients that the clinical implications of pathogenic variants in the moderate risk BRIP1 gene are evolving and that their individual recommendations should be reviewed every 12–18 months to remain current.
Families with an identified pathogenic germline BRIP1 variant should be offered cascade genetic testing to clarify their risk and identify which family members might benefit from tailored recommendations for cancer prevention and early detection.