In the United States, the estimated number of newly diagnosed cases of female breast cancer for 2020 is 276,480. More than a third of patients have tumors that have spread to regional lymph nodes or have distant metastases and survival rates decrease substantially for patients with distant metastasis. The 5-year survival rate for metastatic breast cancer is 28.1%.1 Breast cancer survival varies by molecular subtype (HR [hormone receptor] and HER2 [human epidermal growth factor receptor] status), with patients with triple-negative breast cancer (TNBC) having poor prognosis.2

For patients with Stage IV breast cancer, biomarker testing is crucial for appropriate treatment selection.3 While breast cancer susceptibility gene (BRCA) mutations occur predominantly in TNBC, patients with HR+, HER2– breast cancer may be clinically indicated for testing as well. For metastatic or recurrent disease, a diagnostic workup including germline BRCA mutation status may be appropriate.3

Estimated New Cases of Female Breast Cancer in the US by Subtype and Mutation Status (All Stages)1,4,5

 

Estimated New Cases of Female Breast Cancer in the US
Estimated New Cases of Female Breast Cancer in the US

gBRCAm, germline BRCA mutated; gHRRm, germline homologous recombination repair pathway, mutated; HRRm, homologous recombination repair gene-mutated.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer Testing

NCCN Guidelines® for Breast Cancer: Germline Testing3

Which patients with breast cancer should have germline testing?

Patients with recurrent or metastatic breast cancer

Which genes should be tested?

BRCA1 and BRCA2

Genetic testing can help determine familial risk and eligibility for targeted treatments.6

NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Genetic Testing Recommendations for Breast Cancer6,a

NCCN Guidelines® for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Genetic Testing Recommendations for Breast Cancer
NCCN Guidelines® for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Genetic Testing Recommendations for Breast Cancer

aGenetic testing for high penetrance cancer susceptibility genes. bUnknown or limited family history or ≥1 close blood relative (first-, second-, or third-degree relatives on the same side of the family) with breast cancer, ovarian cancer, pancreatic cancer, or prostate cancer at any age. cAshkenazi Jewish ancestry; or ≥1 close blood relative with breast cancer at ≤50 years or ovarian cancer, pancreatic cancer, or metastatic or intraductal/cribriform histology, or high- or very-high risk group (see NCCN Guidelines for Prostate Cancer7) prostate cancer at any age; or ≥3 total diagnoses of breast cancer in patient and/or close blood relatives.

BRCA Mutation
BRCA Mutation

Learn More About Testing for BRCA Mutations

The BRCA1 and BRCA2 genes play an important role in repairing double-strand breaks (DSBs) in DNA through homologous recombination as part of the highly conserved Fanconi anemia/BRCA DNA damage response pathway.8 Aberrations in DNA repair pathways can lead to damaged DNA and genomic instability.8

PARP Enzymes Play an Important Role in DNA Repair

Single-Strand DNA Break

Poly (ADP-ribose) polymerase (PARP) enzymes play a key role in base excision repair, another major DNA repair pathway.8 PARP enzymes bind to single-strand breaks and recruit repair proteins.9,10 When PARP enzymes are inhibited, single-strand breaks cannot be repaired and may be converted to more cytotoxic DSBs in DNA.10-13

Double-Strand DNA Break

In cells with homologous recombination deficiency, DSBs may no longer be accurately repaired.13

1. Surveillance, Epidemiology, and End Results Program. Cancer stat facts. Accessed October 20, 2020. http://seer.cancer.gov/statfacts/html/breast.html. 2. Surveillance, Epidemiology and End Results Program. Cancer stat facts: female breast cancer. Accessed October 20, 2020. http://seer.cancer.gov/statfacts/html/breast.html. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.2.2021. ©National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed March 12, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 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. 4. Howlader N, et al. J Natl Cancer Inst. 2014;106(5):dju055. doi:10.1093/jnci/dju055. 5. Tung N, et al. J Clin Oncol. 2016;34(13):1460-1468. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic V.2.2021. ©National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed January 15, 2021. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The 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. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.2.2021. ©National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed February 17, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 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. 8. Den Brok WD, et al. JCO Precis Oncol. 2017;1-13. 9. Hoeijmakers JH. Nature. 2001;411(6835):366-374. 10. Murai J, et al. Cancer Res. 2012;72(21):5588-5599. 11. Farmer H, et al. Nature. 2005;434(7035):917-921. 12. Shen Y, et al. J Pharmacol Exp Ther. 2015;353(3):446-457. 13. Polyak K, Garber J. Nat Med. 2011;17(3):283-284.