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Precision Medicine for Breast Cancer

Discover guideline-recommended actionable and emerging biomarkers in breast cancer.

Reading time: 15 min

Biomarker Testing is Transforming the Management of Breast Cancer

Female breast cancer is the fourth leading cause of cancer death in the United States, but
biomarker testing may contribute to lowering premature death from cancer, including breast.1,2

Breast cancer icon

Breast Cancer Biomarker Testing Recommendations Are Integral to Treatment Decisions

NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) recommend testing as standard for all eligible patients.3

Biomarker testing has become an integral part of breast cancer care; the National Comprehensive Cancer Network® (NCCN®) recommends that all patients with newly diagnosed primary or metastatic breast cancer undergo HER2 and HR testing to inform clinical decision making.3 Comprehensive germline and somatic profiling for recurrent and metastatic cancer is also recommended to identify candidates for appropriate therapies.3

Align to NCCN Guidelines® for specific treatment recommendations in each setting.3

NCCN Guidelines for Breast Cancer treatment recommendations
Subtype

Early breast cancer

HR+/HER2-negative

TNBC

If high-riskb after surgery

Actionable biomarkers

Germline BRCA1/2 mutations

gBRCA status may inform surgical decisions

Recurrent unresectable (local or regional) or metastatic diseasec

HR+/HER2-negative

TNBC

HR+/HER2-positivea
and HR-/HER2-positive

HR+/HER2-positive
and HR-/HER2-positive

HER2-positive

PIK3CA activating mutations

AKT1 activating mutation

PTEN inactivating alterations

ESR1 mutation

HER2-low expressiond

Germline BRCA1/2 mutations

PD-L1 expression

HER2-positive

NCCN Guidelines for Breast Cancer treatment recommendations

Subtypes and common
actionable biomarkersa 
across cancer stages

Early breast cancer

HR+/HER2-negative

TNBC

If high riskb 
after surgery

Germline BRCA1/2 mutations

HER2-positive

HR+/HER2-negative

Recurrent unresectable (local or
regional) or metastatic diseasec

gBRCA status may inform surgical decisions

HR+/HER2-positivea and HR-/HER2-positive

PIK3CA activating mutations

ATK1 activating mutations

PTEN inactivating mutations

ESR1 mutations

HER2-low expressiond

Germline BRCA1/2 mutations

TNBC

HER2-low expressiond

Germline BRCA1/2 mutations

PD-L1 expression

HR+/HER2-positive and HR-/HER2-positive

HER2-positive

To view the most recent and complete version of the guideline, go online to NCCN.org.

aHER2-positive: IHC3+ or 2+/ISH+

bHigh-risk criteria include stage II–III TNBC.

cNTRK, RET, TMB and MSI are less common biomarkers that apply to HR+/HER2-negative, TNBC and HER2-positive breast cancers.3–8

dHER2-low: IHC1+ or 2+/ISH-9

AKT1, serine/threonine kinase 1; gBRCA1/2, germline BReast CAncer susceptibility gene 1/2; ESR1, estrogen receptor 1; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; ISH, in situ hybridization; MSI, microsatellite instability; NCCN, National Comprehensive Cancer Network; NTRK, neurotrophic tyrosine receptor kinase; PD-L1, programmed death-ligand 1; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN, phosphatase and tensin homolog; RET, rearranged during transfection; TMB, tumor mutational burden; TNBC, triple-negative breast cancer.

Practice HER2 IHC scoring and view peer-led educational resources.

Visit HER2Know.com
Microscopic slide showing stained cells that are positive for HER2 using immunohistochemistry (IHC)
Biomarker on DNA

Full Knowledge of the Extent of Disease and Biomarkers is Central to Informing Treatment Options3

Non-metastatic invasive breast cancer3

Testing Methodology
BiomarkerNGSPCRISH/FISHIHCGermline sequencing
Subtyping by HR expressionHR+
Established biomarkersHER2-positive (IHC 3+ or 2+/ISH+)
Germline BRCA1/2 mutations
Ki-67

Recurrent unresectable or metastatic breast cancer3

Testing Methodology
BiomarkerNGSPCRISH/FISHIHCGermline sequencing
Subtyping by HR expressionHR+
Established biomarkersHER2-positive (IHC 3+ or 2+/ISH+)
HER2-low (IHC 1+ or 2+/ISH-) expression
Germline BRCA1/2 mutations
PIK3CA activating mutations
AKT1 activating mutation
PTEN inactivating alterations
ESR1 mutation
NTRK fusion
MSI-H/dMMR
TMB-H
RET-fusion
PD-L1
Target icon

The accuracy of results relies on optimal preparation of the biopsy sample, so it is crucial that the multidisciplinary team (MDT) work together to ensure all preanalytical requirements are met.

AKT1, serine/threonine kinase 1; BRCA1/2, BReast CAncer susceptibility gene 1/2; dMMR, deficient mismatch repair; ESR1, estrogen receptor 1; FDA, US Food and Drug Administration; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; ISH, in situ hybridization; Ki-67, antigen Kiel 67; MDT, multidisciplinary team; MSI-H, microsatellite instability high; NGS, next-generation sequencing; NTRK, neurotrophic tyrosine receptor kinase; PCR, polymerase chain reaction; PD-L1, programmed death-ligand 1; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN, phosphatase and tensin homolog; RET, rearranged during transfection; TMB-H, tumor mutational burden high.

DNA and patient icon

HER2 Expression, PIK3CA Activating Mutations, and PD-L1 Are Some of the Most Prevalent Actionable Biomarkers That Can Inform Clinical Decision Making

BiomarkersPrevalenceRelevant subtype
Established biomarkers3HER2-positive (IHC 3+ or 2+/ISH+)~15%9HR+ or HR-3
HER2-low (IHC 1+ or 2+/ISH-) expression~50%9,10HR+ or HR-3
Germline BRCA1/2 mutations~5–10%11–13Any subtype3
PIK3CA activating mutationsUp to 40%14,15HR+/HER2-negative3
AKT1 activating mutation1.4–6.3%16,17
PTEN inactivating alterations~5%15
ESR1 mutation20–40% (metastatic breast cancer)18
NTRK fusion<5%4Any subtype3
MSI-H/dMMR0.6–1.9%7,8
TMB-H5%6
RET-fusion~1.2%5
PD-L150% (metastatic TNBC)19HR-/HER2-negative (TNBC)3
Emerging biomarkers3HER2 (ERBB2) activating mutation11%20,aHR+ or HR-/HER2-negative3
Somatic BRCA1/2 mutationsNot well establishedAny subtype3
Germline PALB2 mutations~1%21Any subtype3

a>90% are HER2 negative (IHC/FISH).20

AKT1, serine/threonine kinase 1; BRCA1/2, BReast CAncer susceptibility gene 1/2; dMMR, deficient mismatch repair; ERBB2, erythroblastic leukemia viral oncogene homolog 2; ESR1, estrogen receptor 1; FDA, US Food and Drug Administration; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization; MSI-H, microsatellite instability high; NTRK, neurotrophic tyrosine receptor kinase; PALB2, partner and localizer of BRCA2; PD-L1, programmed death-ligand 1; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN, phosphatase and tensin homolog; RET, rearranged during transfection; TMB-H, tumor mutational burden high; TNBC, triple-negative breast cancer.

Biomarker on DNA

HER2 Expression, Germline BRCA1/2m, and PIK3CA/AKT1/PTEN Alterations Can Indicate Eligibility for Targeted Treatment in Certain Patients With Breast Cancer22

Assess all eligible patients for actionable biomarkers and find out more about how these can inform care.22

Why test for HER2Why test for BRCA1/2mWhy test for PIK3CA/AKT1/PTEN alterations

AKT1, serine/threonine kinase 1; BRCA1/2m, BReast CAncer susceptibility gene 1/2 mutation; HER2, human epidermal growth factor receptor; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN, phosphatase and tensin homolog.

Guidelines document icon

Considerations for Your Practice

Initiate, action, or review MDT protocols for identifying patients eligible for biomarker testing.3

  • Test for actionable biomarkers in breast cancer including HER2, germline BRCA1/2m, and PIK3CA/AKT1/PTEN alterations3
    • How comprehensively HER2 IHC results are reported can have implications for patient care; it is important to record discrete scores and presence of staining
Gene & I

Visit Gene&i.com for a suite of educational resources to support clinical conversations about genetic testing between you and patients with breast cancer.

Gene&i.com

AKT1, serine/threonine kinase 1; BRCA1/2m, BReast CAncer susceptibility gene 1/2 mutation; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; MDT, multidisciplinary team; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN, phosphatase and tensin homolog.

*This information is intended as educational and is not intended as a complete list of available testing options. AstraZeneca is not responsible for any test provider and does not endorse any particular diagnostic test. The accuracy and results of diagnostic tests vary, and AstraZeneca shall have no liability arising from such testing. Information provided herein should in no way be considered a guarantee of coverage, reimbursement, or patient assistance. Providers should contact third-party laboratories for information on their patient assistance programs. While diagnostic testing may assist providers in identifying appropriate treatment for patients, the decision and action should be decided by a provider in consultation with the patient. All products are trademarks of their respective holders, all rights reserved.

Helpful Resources

Check out these featured resources on biomarker testing in breast cancer.

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2:15 min

FOR PATIENTS

Gene&i: What is genetic testing?

Share this video with patients with breast cancer covering how genetic mutations can play a pivotal role in breast cancer care and what they may mean for patients.

1:54 min

FOR PATIENTS

Gene&i: Why is genetic testing important in breast cancer?

Share this video with patients with breast cancer to increase understanding of what genetic testing involves and how they may benefit from the results.

Gene&amp;i: Clinical Conversation Aid
42.9 MB

FOR PATIENTS

Gene&i: Clinical Conversation Aid

Share this resource with your patients to help them understand the value of genetic testing on their breast cancer care.

View more resources 

References

  1. National Cancer Institute. Cancer Stat Facts: Female Breast Cancer. Accessed May 22, 2024: https://seer.cancer.gov/statfacts/html/breast.html
  2. D’Avó Luis AB and Seo MK. Eur J Health Econ. 2021;22:789–810.
  3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.6.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed November 11, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org.
  4. Kim J, et al. Cancer Res. 2022;82(4_Supplement):P3-12–08.
  5. Pecar G, et al. Breast Cancer Res. 2023;25:26.
  6. Barroso-Sousa R, et al. Cancers. 2023;15:3997.
  7. Vidula N, et al. npj Breast Cancer. 2022;8:117.
  8. Cheng AS, et al. Breast Cancer Res Treat. 2020;179:3–10.
  9. Tarantino P, et al. Cancer Discov. 2020;38(17):1951–1962.
  10. Schettini F, et al. NPJ Breast Cancer. 2021;7(1):32.
  11. Høberg-Vetti H, et al. Eur J Hum Genet. 2016;24:881–888.
  12. Winter C, et al. Ann Oncol. 2016;27:1532–1538.
  13. Shao C, et al. Abstract presented at: American Society of Clinical Oncology Annual Meeting; 4–8 June, 2021; virtual. Abstract 10589.
  14. Cizkova M, et al. Breast Cancer Res. 2012.14:R28.
  15. Li G, et al. PloS ONE.13(9):e0203495.
  16. Rudolph M, et al. BMC Cancer. 2016;16:622.
  17. Stemke-Hale K, et al. Cancer Res. 2008;68(15):6084–6091.
  18. Dustin D, et al. Cancer. 2019;125(21):3714–3728.
  19. Oner G, et al. World J Surg Oncol. 2021;19(1).
  20. Deniziaut G, et al. Oncotarget. 2016;7(45):73337–73346.
  21. Yadav S, et al. J Clin Oncol. 2023;41(9):1703–1713.
  22. Subhan MA, et al. Cancers. 2024;15:2204.

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.