BARD1

 

BARD1-Related Cancer Risk

The BARD1 gene is classified as a “moderate risk” gene, meaning that there is possibly a modestly increased risk for certain types of cancers.  For example, women who have a BARD1 pathogenic gene mutation may be 2-3 times more likely to develop breast cancer.  Data regarding a potential association between BARD1 gene mutations and ovarian cancer risk have been inconsistent.  Further research is needed to understand the interactions of moderate risk genes and family history on lifetime cancer risk.

 

BARD1 cancer screening and risk-reducing options

The best long-term medical management for individuals who carry a mutation in the BARD1 gene is a topic of on-going research.  Healthcare providers oftentimes rely on an individual’s personal and family history to guide medical care.

  • Breast: Women should pursue standard clinical breast exams and mammography.  Depending upon personal and family history, some women may also consider increased breast cancer surveillance with breast MRI.
  • Ovary: There is no evidence that ovarian cancer screening with currently available methods (e.g. transvaginal ultrasound and CA-125 blood measurement) reduces ovarian cancer mortality. Due to conflicting data, no definitive recommendation for risk-reducing surgery exists at this time.

 

BARD1 associated therapeutic/ treatment implications

Individuals who have a cancer diagnosis and an identified BARD1 pathogenic mutation should speak with their treating physician about the availability of targeted/ personalized treatment options.

Clinical trials evaluating different medications in individuals who have pathogenic mutations in BARD1 and/or other related genes might be available now or in the future.

 

BARD1 testing in other family members

At this point in time, testing adult family members for a moderate risk gene mutation does NOT provide the same clarity or guidance that testing for a high risk gene mutation does. This is because moderate risk gene mutations should not be assumed to be the sole explanation for a particular family’s history of cancer.  For example, a family could have additional unidentified genetic and/or non-genetic risk factors contributing to the development of cancer seen in family members.  It is recommended that family members discuss risks, benefits and limitations of genetic testing with their physician and/or genetic counselor.  If an adult family member were to test positive for the familial BARD1 gene mutation, increased cancer screening might be considered.  However, given the current lack of data regarding BARD1 gene mutations, if an adult family member were to test negative for a familial BARD1 gene mutation, that individual may still be at increased risk for cancer depending upon the family history and possibility for other genes to be playing a role.  Cancer screening should be performed in accordance with the family history until further data is available.

 

Future considerations

As research and data on cancer risk estimates continue to evolve, physicians and researchers will gain a better understanding of how a BARD1 gene mutation influences medical care.  Because the information provided to patients will almost certainly change, those with a BARD1 gene mutation are encouraged to keep in touch with their medical providers in order to receive updates.

 

 

References:

  1. Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016;13(9):581-8. doi: 10.1038/nrclinonc.2016.90. PubMed PMID: 27296296.
  2. Norquist BM, Harrell MI, Brady MF, Walsh T, Lee MK, Gulsuner S, et al. Inherited Mutations in Women with Ovarian Carcinoma. JAMA Oncol. 2016 Apr;2(4):482-90.
  3. Slavin TP, Maxwell KN, Lilyquist J, Vijai J, Neuhausen SL, Hart SN, et al. The contribution of pathogenic variants in breast cancer susceptibility genes to familial breast cancer risk. NPJ Breast Cancer. 2017 June 9;3:22.
  4. Couch FJ, Shimelis H, Hu C, Hart SN, Polley EC, Na J, et al. Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. JAMA Oncol. 2017 Sep 1;3(9):1190-1196.
  5. Ramus SJ, Song H, Dicks E, Tyrer JP, Rosenthal AN, Intermaggio MP, et al. Germline mutations in the BRIP1, BARD1, PALB2, and NBN genes in women with ovarian cancer. J Natl Cancer Inst. 2015 Aug 27;107(11).
  6. Kurian AW, Hughes E, Handorf EA, Gutin A, Allen B, Hartman AR, et al. Breast and Ovarian Cancer Penetrance Estimates Derived From Germline Multiple-Gene Sequencing Results in Women.  JCO Precision Oncology. 2017 June 27;1:1-12.