Know your patient’s advanced breast cancer with NGS testing.

Recognize the impact of actionable alterations.

Understand the prevalence and impact of PIK3CA, AKT1, and PTEN alterations in HR+/HER2- advanced breast cancer.

Uncover the potential of NGS testing.

Learn how NGS testing can open more possibilities for your patients.

Discover best practice on testing in advanced breast cancer.

Explore an overview of NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines^®) recommendations.

AKT1, serine/threonine protein kinase 1; HER2-, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN, phosphatase and tensin homolog.

Uncover key actionable biomarkers in advanced breast cancer with NGS testing.^1,2

PIK3CA, AKT1, and PTEN alterations can be predictive of treatment resistance in advanced breast cancer.^3–5,a

The PI3K/AKT/PTEN pathway mediates critical cellular processes, such as cell proliferation, cell survival and cell metabolism, and is relevant in HR+/HER2- advanced breast cancer.^3–5,a

Hyperactivation of PI3K/AKT/PTEN pathway signaling promotes resistance to many breast cancer treatments, including endocrine therapies (ET) and CDK4/6is.^3–5

Most patients with HR+/HER2- advanced breast cancer experience disease progression on ET ± CDK4/6i.⁶

Adapted from Paplomata E, O’Regan R. Ther Adv Med Oncol. 2014;6(4):154-166.

Alterations leading to hyperactivation of the PI3K/AKT/PTEN pathway in HR+/HER2- advanced breast cancer.^3,7–9

Gene	Key genomic event	Change in protein function
PIK3CA	Point mutations of PIK3CA	Gain of function of PI3K
AKT1	Point mutation of AKT1	Gain of function of AKT
PTEN	Point mutations, large deletions, and genomic rearrangements involving PTEN	Loss of function of PTEN

SCROLL

NCCN Guidelines^® recommend testing for PIK3CA, AKT1, and PTEN alterations in eligible patients with HR+/HER2- advanced breast cancer.¹⁰

Take a closer look at common drivers of disease progression in patients with HR+/HER2- advanced breast cancer.^3,8,9,11

Never miss a mark in advanced breast cancer.

Uncover actionable alterations such as PIK3CA, AKT1, and PTEN with NGS.¹⁰

^aAdvanced breast cancer is defined as locally advanced breast cancer and metastatic breast cancer.

AKT, serine/threonine protein kinase; AKT1, serine/threonine protein kinase 1; CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; mTOR, mammalian target of rapamycin; NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing; PI3K, phosphoinositide 3-kinase; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN, phosphatase and tensin homolog.

Get a detailed picture of your patient’s advanced breast cancer with NGS.

Testing for actionable biomarkers, including PIK3CA, AKT1, and PTEN alterations, can provide a detailed picture of a patient’s HR+/HER2- advanced breast cancer^a and guide their clinical management.^7,10,12–14

For patients with recurrent or metastatic breast cancer, the NCCN Guidelines recommend comprehensive germline and somatic profiling, such as next-generation sequencing (NGS) testing.¹⁰

NGS can give you access to:

Predictive information

Hyperactivation of the PI3K/AKT/PTEN signaling pathway drives resistance to endocrine therapies.^3,4

Indicates likelihood of response to certain targeted treatments.⁵

Prognostic information

In mBC, PIK3CA mutations have been linked with aggressive disease and poor prognosis.^12,15

In breast cancer, emerging evidence suggests PTEN alterations may be associated with progression and poor prognosis.¹⁶

Which can inform:

Treatment eligibility

Informs eligibility for FDA-approved targeted treatments.¹⁰

Trial eligibility

Informs clinical trial eligibility for targeted treatments.^7,13

The NCCN Guidelines currently recommend NGS testing for the following biomarkers in advanced breast cancer.^10,a

Biomarkers with FDA-approved therapies:

PIK3CA activating mutations
AKT1 activating mutation
ESR1 mutations
PTEN alterations
NTRK fusion
MSI-H/dMMR
TMB-H
RET-fusion

Evolving treatment options are rewriting the rules of who may be eligible for targeted therapy; ensure no appropriate patients miss out.

The biomarker-driven treatment landscape is continuously evolving, increasing the number and type of patients now eligible for personalized treatments selected by NGS testing.^17,18 With increased options, more patients have the opportunity to access targeted treatments for their cancer than ever before.

Open up possibilities for your patients.

Ensure every eligible patient with HR+/HER2- advanced breast cancer gets the opportunity for NGS testing to help inform personalized treatment strategies.

Despite its potential to inform treatment decisions, not all patients receive NGS testing.^19–21

Although some evidence suggests that NGS testing rates are steadily increasing in clinical practice,^19,22 a retrospective observational study assessing NGS testing patterns found that only 40% of patients with mBC received testing between 2017 and 2023.^21,b

Ensure your eligible patients don’t miss out.

How can you make more informed treatment decisions with NGS testing?

^aAdvanced breast cancer is defined as locally advanced breast cancer and metastatic breast cancer. ^bRetrospective observational study of 9,669 patients with HR+/HER2-negative mBC from the Flatiron Health Database and Flatiron Health-Foundation Medicine clinicogenomic database, evaluating NGS testing rates between January 2017 and June 2023.²¹

AKT, serine/threonine protein kinase; AKT1, serine/threonine protein kinase 1; dMMR, deficient mismatch repair; ESR1, estrogen receptor 1; FDA, US Food and Drug Administration; HER2-, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; mBC, metastatic breast cancer; MSI-H, microsatellite instability-high; NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing; NTRK, neurotrophic tropomyosin receptor kinase; PI3K, phosphoinositide 3-kinase; 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.

Be prepared for disease progression with early NGS testing.

Test all eligible patients with advanced breast cancer^a at diagnosis to help inform future clinical decision-making upon disease progression.¹⁰

NCCN Guideline recommendations for initial patient work-up for advanced breast cancer^10,a:

When?

Initial workup for patients with stage IV (M1) or recurrent unresectable breast cancer.

How?

Comprehensive germline and somatic profiling techniques, such as next-generation sequencing (NGS) panel testing.

Consider starting the discussion on standardizing reflex NGS testing protocols with your MDT.

Start a discussion with your MDT about whether incorporating reflex NGS testing during the initial patient workup could enhance your institution's ability to provide guideline-concordant care.²³

Reflex protocols simplify the testing process, reduce wait times for test ordering and may improve testing rates, helping to increase the number of patients identified for targeted therapy.^23–25

Be prepared. Test at metastatic diagnosis with NGS.

^aAdvanced breast cancer is defined as locally advanced breast cancer and metastatic breast cancer.

MDT, multidisciplinary team; NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing.

For more information on biomarker testing in HR+/HER2- advanced breast cancer^a:

National Comprehensive Cancer Network^® (NCCN^®) recommendations for biomarker testing for recurrent unresectable (local or regional) or stage IV (M1) disease.

Download this resource to understand the NCCN Guidelines recommendations for biomarker testing for recurrent unresectable (local or regional) or stage IV (M1) disease.

[Title of resource]

[Description of vide goes here lorem ipsum cae prae rem quunt prepuda ntiurep recest hitissum aut assunto odiciis etum quam re, sam re conet reicae netur atemo exerum]

slide-1
slide-2

^aAdvanced breast cancer is defined as locally advanced breast cancer and metastatic breast cancer.

HER2-, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive.

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.

References

1. Burstein HJ, et al. J Clin Oncol. 2024;42(12):1450–1453. 2. FoundationOne^®CDx. Technical Information. Accessed April 20, 2025. https://www.foundationmedicine.com/sites/default/files/media/documents/2025-04/RAL-0003_v31%20F1CDx%20Tech%20Label_P170019S054_clean_final.docx.pdf. 3. Miricescu D, et al. Int J Mol Sci. 2020;22(1):173. 4. Paplomata E, O'Regan R. Ther Adv Med Oncol. 2014;6(4):154–166. 5. Martorana F, et al. Front Pharmacol. 2021;12:662232. 6. Cogliati V, et al. Life (Basel). 2022;12(3):378. 7. Chakravarty D, et al. J Clin Oncol. 2022;40(11):1231–1258. 8. Smyth LM, et al. Cancer Discov. 2020;10(4):526–535. 9. Chen J, et al. Front Oncol. 2022;12:825484. 10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer V.4.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed April 25, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. 11. Razavi P, et al. Cancer Cell. 2018;34(3):427–438.e6. (Suppl Appendix). 12. Sobhani N, et al. J Cell Biochem. 2018;119(6):4287–4292. 13. Vidwans SJ, et al. Oncoscience. 2014;1(10):614–623. 14. Li H, et al. Cancers (Basel). 2021;13(14):3517. 15. Mollon LE, et al. Clinical Breast Cancer. 2020;20(3):e232–e243. 16. Li S, et al. Oncotarget. 2017;8(19):32043–32054. 17. IQVIA. Global Oncology Trends 2021. Accessed April 30, 2025. https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/global-oncology-trends-2021. 18. PMC. The Evolution Of Biomarker Use In Clinical Trials For Cancer Treatments. Accessed April 30, 2025. https://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/The_Evolution_of_Biomarker_Use_in_Clinical_Trials_for_Cancer_Treatments.pdf#:~:text=Among%20the%20most%20significant%20findings%20are%20that%2055,less%20expensive%20for%20systems%20that%20incor-porate%20personalized%20medicine. 19. Vanderwalde AM, et al. J Clin Oncol. 2021;39(28)_suppl, 288–288. 20. McDonald ES, et al. J Nucl Med. 2016;57:9S–16S. 21. Park L, et al. Presented at American Society of Clinical Oncology Annual Meeting 2024, Chicago, IL: P1041. 22. Sturgill EG, et al. JCO Precis Oncol. 2021;5:1297–1311. 23. Gosney JR, et al. ESMO Open. 2023;8(4):101587. 24. Cripps AP, Prakash A. J Clin Oncol. 2024;42(16_suppl):e23302. 25. Dowdell AK, et al. JCO Oncol Pract. 2024;20(11):1523–1532.