Multiple clinical practice guidelines point to the importance of genetic testing for certain patients with breast cancer, to inform treatment decisions and preventative interventions .
Testing is generally offered solely to those at risk of BRCA mutation based on hereditary risk or where the status will affect clinical management.6
Which subpopulations are more likely to have a BRCA mutation?
Breast cancer patients can be categorised into subpopulations by considering the status of their associated hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) biomarkers.7
The NCCN Guidelines® for Breast Cancer make recommendations for targeted therapies in patients with TNBC and HR+/HER2- subtypes of recurrent or mBC based on biomarker testing.2
The prevalence of germline BRCA mutations in breast cancer patients varies between biomarker subpopulations.8-10 Generally, BRCA is typically associated with TNBC patients, as a larger proportion of these patients show gBRCA mutations. However, the prevalence of HR+/HER2- disease accounts for the largest overall breast cancer disease group, at around 70%.10-12 Among almost 400 patients with HER2+ BC, 4% were found to have a gBRCA mutation.10
Literature suggests that BRCA testing to help inform treatment decisions should be performed as early as possible and within a reasonable turnaround time, in order for the results to be used effectively.6
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
ABC, advanced breast cancer; ASCO, American Society of Clinical Oncology; BC, breast cancer; BRCA, breast cancer gene, ESMO, European Society for Medical Oncology; gBRCA, germline BRCA; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; mBC, metastatic breast cancer; NCCN, National Comprehensive Cancer Network; SGO, Society of Gynecologic Oncology; TNBC, triple negative breast cancer.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic V1.2020. National Comprehensive Cancer Network, Inc. All rights reserved. [Accessed February 2021]. To view the most recent and complete version of the guideline go online to NCCN.org.
- Referenced with permission from the NCCN Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V6.2020. National Comprehensive Cancer Network, Inc. All rights reserved. [Accessed February 2021]. To view the most recent and complete version of the guideline go online to NCCN.org.
- Lu KH et al. J Clin Oncol. 2014; 32: 833-840.
- Lancaster JM et al. Gynecol Oncol. 2015; 136: 3-7.
- Cardoso F et al. Ann Oncol. 2018: 29; 1634-1657.
- Hoogerbrugge N and Jongmans MC. Eur J Hum Genet. 2016; 24: S19-S26.
- Gong Y et al. Sci Rep. 2017: 7; 1-10.
- Billar J et al. Annals of Surgical Oncology. 2010: 17; S384-S390.
- The Cancer Genome Atlas Network. Nature. 2012; 490: 61-70.
- Eccles D et al. Ann Oncol. 2016; 27: 467-473.
- Howlader N et al. J Natl Cancer Inst. 2014; 106; 1-8.
- American Cancer Society. Breast Cancer: Facts and Figures 2019-2020. Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2019-2020.pdf [Accessed February 2021].
Some patients will have no immediate family history of BRCA-related cancers, such as breast or prostate cancer, but may still be carriers of a mutation, increasing their risk of developing cancer.
In the pedigree diagram, above, we can see that patient A is a carrier of a gBRCA mutation, despite his parents not having a cancer diagnosis. It is only when you delve further back into the family history of the patient, that you find patient A’s grandfather had a cancer diagnosis, which was most likely the trigger for patient A’s BRCA mutation status. As a result, patient A may have passed on this mutation to his offspring, making them prime candidates for a BRCA test.
Patients may be unaware of their BRCA mutation testing, highlighting the importance of testing even if an immediate family member has not had a cancer diagnosis.
Remember to also keep several traits in mind for BRCA testing as not all are ‘commonly assumed traits’, including a family history of pancreatic and/or prostate cancer.