Other Biomarkers in BC

Other biomarkers in BC can help inform treatment decisions and assess cancer risk.1

Predictive biomarkers

 

HER22,3

HER2 is a growth factor that typically plays a role in cell proliferation and differentiation
HER2 is a growth factor that typically plays a role in cell proliferation and differentiation

HER2 is a growth factor that typically plays a role in cell proliferation and differentiation. Overexpression of the HER2 protein or amplification of the HER2 gene can lead to the development of BC.3 Guidelines recommend testing for HER2 gene amplification using ISH or HER2 protein overexpression using IHC.4

Prevalence in BC: ≈15% of patients5

FDA-approved assays to detect HER2 amplification6:

  • FoundationOne®CDx
  • PathVysion HER-2 DNA Probe Kit
  • PATHWAY anti-Her2/neu (4B5) Rabbit Monoclonal Primary Antibody
  • Bond Oracle HER2 IHC System
  • HER2 CISH pharmDx Kit
  • INFORM HER2 Dual ISH DNA Probe Cocktail
  • HercepTest
  • HER2 FISH pharmDx Kit

In patients with BC, HER2 amplification and/or overexpression can identify patients eligible for targeted therapies.1

Hormone receptors (ER and PR)2,7

Activation of the hormone receptors ER and PR can drive gene transcription that promotes cell proliferation
Activation of the hormone receptors ER and PR can drive gene transcription that promotes cell proliferation

Activation of the hormone receptors ER and PR can drive gene transcription that promotes cell proliferation.2 Guidelines recommend testing for ER and PR using IHC.1

Prevalence in BC: >80% of patients5

In patients with BC, HR status can identify patients likely to respond to hormonal therapy.1

PD-L1

PD-L1 is an immune checkpoint molecule that binds to PD-1 and thereby inhibits T-cell activity
PD-L1 is an immune checkpoint molecule that binds to PD-1 and thereby inhibits T-cell activity

PD-L1 is an immune checkpoint molecule that binds to PD-1 and thereby inhibits T-cell activity.8 Some tumor cells upregulate PD-L1 expression, which suppresses immune surveillance and allows for tumor growth.8

Prevalence in TNBC: ≈10% to ≈60%, based on the assay and scoring cutoffs used9,10

FDA-approved assay to detect PD-L1 expression6:

  • Ventana PD-L1 (SP142) Assay

NTRK12,13

The NTRK genes, NTRK1, NTRK2, and NTRK3, encode for TRK proteins, which are nerve growth factor receptors
The NTRK genes, NTRK1, NTRK2, and NTRK3, encode for TRK proteins, which are nerve growth factor receptors

The NTRK genes, NTRK1, NTRK2, and NTRK3, encode for TRK proteins, which are nerve growth factor receptors.13,14 The NTRK gene may undergo rearrangement with another gene, resulting in a fusion protein.12 TRK fusion proteins are oncogenic drivers, which constitutively activate multiple signaling pathways that promote tumor growth and survival.11-14

Prevalence in invasive breast cancer: <1% of patients15

Prevalence in secretory breast cancer: >90% of patients12

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing certain patients with mBC for biomarkers such as BRCA1/2 (germline), ER, PR, HER2, PIK3CA, and PD-L1.16

Predispositional biomarkers


Multigene panels

Multigene panels are available to test for pathogenic or likely pathogenic mutations associated with inherited susceptibility to cancer.17

NCCN Guidelines® state that the following mutations may be associated with a risk of developing BC:

Gene17 Function
CDH1* Cell adhesion18
CHEK2 DNA repair and cell cycle regulation19
ATM DNA repair20
NBN DNA repair21
PALB2 DNA repair22
NF1 Tumor suppressor gene23
PTEN Tumor suppressor gene24
STK11 Tumor suppressor gene25
TP53 Tumor suppressor gene26

*Associated with increased risk of lobular breast cancer.

To optimize turnaround time and cost efficiency, some laboratories offer testing for BRCA mutations first, then automatically reflex to a larger multigene panel if the BRCA mutation test returns negative results.27

Different multigene panels may test for different sets of genes; therefore, panel tests should be chosen carefully.17

 

AKT, protein kinase B; ATM, ataxia-telangiectasia mutated; BRCA, breast cancer susceptibility gene; CDH1, cadherin-1; CHEK2, checkpoint kinase 2; DAG, diacylglycerol; ER, estrogen receptor, ERK, extracellular signal–related kinase; FDA, Food and Drug Administration; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; ISH, in situ hybridization; mBC, metastatic breast cancer; MEK, mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; NBN, nibrin; NCCN, National Comprehensive Cancer Network; NF1, neurofibromin 1; NTRK, neurotrophic tyrosine kinase; PALB2, partner and localizer of BRCA2; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PI3K, phosphoinositide 3-kinase; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; PKC, protein kinase C; PLC, phospholipase C; PR, progesterone receptor; PTEN; phosphatase and tensin homolog; RAF, v-Raf-1 murine leukemia viral oncogene homolog; STK11, serine/threonine kinase 11; TNBC, triple-negative breast cancer; TP53, tumor protein 53; TRK, tropomyosin receptor kinase.

 

References: 1. Hammond MEH et al. Arch Pathol Lab Med. 2010;134(7):e48-e72. 2. Rosenbaum JN et al. Am J Pathol. 2017;187(10):2185-2198. 3. Shah S et al. Patholog Res Int. 2010;2011:903202. 4. Wolff AC et al. J Clin Oncol. 2018;36(20):2105-2122. 5. Howlader N et al. J Natl Cancer Inst. 2014;106(5). 6. FDA. https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm. Accessed September 5, 2018. 7. Daniel AR et al. Expert Rev Endocrinol Metab. 2011;6(3):359-369. 8. Chen DS et al. Clin Cancer Res. 2012;18(24):6580-6587. 9. Schmid P et al. N Engl J Med. 2018;379(22):2108-2121. 10. Stovgaard ES et al. Breast Cancer Res Treat. 2019;174(3):571-584. 11. Amatu A et al. ESMO Open. 2016;1(2):e000023. 12. Vaishnavi A et al. Cancer Discov. 2015;5(1):25-34. 13. Desai A et al. Cancer Biol Med. 2016;13(1):77-86. 14. Bansal P et al. Front Oncol. 2016;6:112. 15. Remoué A et al. Pathol Int. 2019;69(2):94-96. 16. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V3.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 16, 2020. 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. 17. 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. 2019. All rights reserved. Accessed March 3, 2020. 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. 18. Berx G et al. Hum Mutat. 1998;12(4):226-237. 19. Vahteristo P et al. Am J Hum Genet. 2002;71(2):432-438. 20. Khanna KK. J Natl Cancer Inst. 2000;92(10):795-802. 21. Leng S et al. Cancer Res. 2008;68(8):3049-3056. 22. Sy SMH et al. Proc Natl Acad Sci USA. 2009;106(17):7155-7160. 23. Cichowski K et al. Cell. 2001;104(4):593-604. 24. Di Cristofano A et al. Cell. 2000;100(4):387-390. 25. Pappas K et al. Mol Cancer Res. 2017;15(8):1051-1062. 26. Miller LD et al. Proc Natl Acad Sci USA. 2005;102(38):13550-13555. 27. Stanislaw C et al. Cancer Biol Med. 2016;13(1):55-67.

 

Back to top