Biomarker Testing in Breast Cancer Care

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

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 Biomarker Testing Recommendations Are Integral to Treatment Decisions

NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines^®) recommend testing 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 Multigene panel testing (MGPT) (somatic and germline) for recurrent and metastatic cancer is also recommended to identify candidates for appropriate therapies.³

Testing Methodology

Biomarker

NGS

PCR

ISH/FISH

IHC

Germline sequencing

Subtyping by HR expression

HR+

Established

biomarkers

HER2-positive (IHC 3+ or 2+/ISH+)

Germline BRCA1/2 mutations

Ki-67

Testing Methodology

Biomarker

NGS

PCR

ISH/FISH

IHC

Germline sequencing

Subtyping by HR expression

HR+

Established

biomarkers

HER2-positive (IHC 3+ or 2+/ISH+)

HER2-low (IHC 1+ or 2+/ISH-) expression

Germline BRCA1/2 mutations

Germline PALB2 mutations

ESR1 mutation

PIK3CA activating mutations

AKT1 activating mutation

PTEN inactivating alterations

NTRK fusion

MSI-H/dMMR

TMB-H

RET-fusion

PD-L1

	Biomarkers	Prevalence	Relevant subtype
Established biomarkers³	HER2-positive (IHC 3+ or 2+/ISH+)	~15%⁹	HR+ or HR-³
HER2-low (IHC 1+ or 2+/ISH-) expression	~50%^9,10	HR+ or HR-³
Germline BRCA1/2 mutations	~5–10%^11–13	Any subtype³
Germline PALB2 mutations	~1%¹⁴	Any subtype³
ESR1 mutation	20–40% (metastatic breast cancer)^15,a	HR+/HER2-negative³
PIK3CA activating mutations	Up to 40%^16,17
AKT1 activating mutation	1.4–6.3%^18,19
PTEN inactivating alterations	~5%¹⁷
NTRK fusion	<5%⁴	Any subtype³
MSI-H/dMMR	0.6–1.9%^7,8
TMB-H	5%⁶
RET-fusion	~1.2%⁵
PD-L1	50% (metastatic TNBC)²⁰	HR-/HER2-negative (TNBC)³
Emerging biomarkers³	HER2 (ERBB2) activating mutation	11%^21,b	HR+ or HR-/HER2-negative³
Somatic BRCA1/2 mutations	~1.2%^22,c	Any subtype³
FGRFR1-3 fusion/mutation	~15%²³	Any subtype³

Biomarkers

Prevalence

Relevant subtype

Established

biomarkers³

HER2-positive (IHC 3+ or 2+/ISH+)

~15%⁹

HR+ or HR-³

HER2-low (IHC 1+ or 2+/ISH-) expression

~50%^9,10

HR+ or HR-³

Germline BRCA1/2 mutations

~5–10%^11–13

Any subtype³

Germline PALB2 mutations

~1%¹⁴

Any subtype³

ESR1 mutation

20–40% (metastatic breast cancer)^15,a

HR+/HER2-negative³

PIK3CA activating mutations

Up to 40%^16,17

AKT1 activating mutation

1.4–6.3%^18,19

PTEN inactivating alterations

~5%¹⁷

NTRK fusion

<5%⁴

Any subtype³

MSI-H/dMMR

0.6–1.9%^7,8

TMB-H

5%⁶

RET-fusion

~1.2%⁵

PD-L1

50% (metastatic TNBC)²⁰

HR-/HER2-negative (TNBC)³

Emerging

biomarkers³

HER2 (ERBB2) activating mutation

11%^21,b

HR+ or HR-/HER2-negative³

Somatic BRCA1/2 mutations

~1.2%^22,c

Any subtype³

FGRFR1-3 fusion/mutation

~15%²³

Any subtype³

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, ESR1 mutations, 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

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

Find a Testing Lab which can perform biomarker testing for your patients*

AKT1, serine/threonine kinase 1; BRCA1/2m, BReast CAncer susceptibility gene 1/2 mutation; ESR1, estrogen receptor 1; 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.

National Cancer Institute. Cancer Stat Facts: Female Breast Cancer. Accessed November 24, 2025. https://seer.cancer.gov/statfacts/html/breast.html
D Avó Luís AB, Seo MK. Eur J Health Econ. 2021;22:789–810.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer V.2.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed February 27, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org.
Kim J, et al. Cancer Res. 2022;82(4_Supplement):P3-13–08.
Pecar G, et al. Breast Cancer Res. 2023;25:26.
Barroso-Sousa R, et al. Cancers (Basel). 2023;15:3997.
Vidula N, et al. NPJ Breast Cancer. 2022;8:117.
Cheng AS, et al. Breast Cancer Res Treat. 2020;179:3–10.
Tarantino P, et al. J Clin Oncol. 2020;38(17):1951–1962.
Schettini F, et al. NPJ Breast Cancer. 2021;7(1):1.
Høberg-Vetti H, et al. Eur J Hum Genet. 2016;24:881–888.
Winter C, et al. Ann Oncol. 2016;27:1532–1538.
Shao C, et al. Abstract presented at: American Society of Clinical Oncology Annual Meeting; 4–8 June, 2021; virtual. Abstract 10589.
Yadav S, et al. J Clin Oncol. 2023;41(9):1703–1713.
Dustin D, et al. Cancer. 2019;125(21):3714–3728.
Cizkova M, et al. Breast Cancer Res. 2012;14:R28.
Li G, et al. PLoS One. 2018;13(9):e0203495.
Rudolph M, et al. BMC Cancer. 2016;16:622.
Stemke-Hale K, et al. Cancer Res. 2008;68(15):6084–6091.
Oner G, et al. World J Surg Oncol. 2021;19(1):264.
Deniziaut G, et al. Oncotarget. 2016;7(45):73337–73346.
Balmaña J, et al. Breast Cancer Res Treat. 2023;204(2):237-248. doi:10.1007/s10549-023-07165-x
Zhang P, et al. J Hematol Oncol. 2024;17:39.
Subhan MA, et al. Cancers (Basel). 2023;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.

Precision Medicine for Breast Cancer

Biomarker Testing is Transforming the Management of Breast Cancer

Breast Cancer Biomarker Testing Recommendations Are Integral to Treatment Decisions

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

Early breast cancer

HR+/HER2-negative

TNBC

If high-risk after surgery

Germline BRCA1/2 mutations

gBRCA status may inform surgical decisions

Recurrent unresectable (local or regional) or metastatic disease^b

HR+/HER2-negative

TNBC

HR+/HER2-positive^a
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 expression^c

Germline BRCA1/2 mutations

PD-L1 expression

HER2-positive

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

HER2 Expression, ESR1 Mutations, PIK3CA Activating Mutations, and PD-L1 Are Some of the Most Prevalent Actionable Biomarkers That Can Inform Clinical Decision Making

HER2 Expression, Germline BRCA1/2m, ESR1 Mutations, and PIK3CA/AKT1/PTEN Alterations Can Indicate Eligibility for Targeted Treatment in Certain Patients With Breast Cancer²⁴

Considerations for Your Practice

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Precision Medicine for Breast Cancer

Biomarker Testing is Transforming the Management of Breast Cancer

Breast Cancer Biomarker Testing Recommendations Are Integral to Treatment Decisions

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

Early breast cancer

HR+/HER2-negative

TNBC

If high-risk after surgery

Germline BRCA1/2 mutations

gBRCA status may inform surgical decisions

Recurrent unresectable (local or regional) or metastatic diseaseb

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 expressionc

Germline BRCA1/2 mutations

PD-L1 expression

HER2-positive

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

HER2 Expression, ESR1 Mutations, PIK3CA Activating Mutations, and PD-L1 Are Some of the Most Prevalent Actionable Biomarkers That Can Inform Clinical Decision Making

HER2 Expression, Germline BRCA1/2m, ESR1 Mutations, and PIK3CA/AKT1/PTEN Alterations Can Indicate Eligibility for Targeted Treatment in Certain Patients With Breast Cancer24

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

Recurrent unresectable (local or regional) or metastatic disease^b

HR+/HER2-positive^a
and HR-/HER2-positive

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

HER2-low expression^c

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

HER2 Expression, Germline BRCA1/2m, ESR1 Mutations, and PIK3CA/AKT1/PTEN Alterations Can Indicate Eligibility for Targeted Treatment in Certain Patients With Breast Cancer²⁴