COMPREHENSIVE BIOMARKER TESTING FOR mBC
TAKE A DEEPER LOOK

Biomarker testing may be what’s missing from an optimized treatment plan for metastatic breast cancer (mBC)

EARLY AND COMPREHENSIVE BIOMARKER TESTING IS AN IMPORTANT FIRST STEP IN THE DIAGNOSIS AND TREATMENT PLANNING OF mBC1

Biomarker testing is critical for optimizing patient care1,2

Biomarker testing may provide actionable information for timely identification of the tumor’s genomic profile, allowing for a more personalized and precise approach to treatment.1,2

Understanding a patient’s tumor profile via next-generation sequencing (NGS) could be an important early step when developing an effective treatment plan.3,4

NGS TESTING ALLOWS FOR THE DETECTION OF A WIDE RANGE OF MUTATIONS4-6

ALTERATIONS IN MULTIPLE GENES HAVE BEEN IDENTIFIED THAT CAN BE EASILY AND COMPREHENSIVELY DETECTED BY NGS, INCLUDING:
  • BRCA4
  • ESR15
  • PIK3CA5,6
  • PTEN5
  • AKT5

"Thorough genomic characterization of metastases will yield valuable insight into the active molecular processes in metastatic disease, which is crucial to understand the effects of systemic treatment on the tumour genome and ultimately to improve treatment of mBC patients."

—Angus L, et al. Nat Genet. 2019.7

THE PI3K PATHWAY IS THE MOST FREQUENTLY ALTERED PATHWAY IN HR+ BC AND HAS BECOME AN IMPORTANT THERAPEUTIC TARGET OVER THE PAST DECADE5,6,8

There is a high prevalence of patients with PIK3CA mutations in HR+/HER2-, the most prevalent breast cancer subtype5

*A range of 30% to 45% has been reported.

The presence of a PIK3CA mutation in the tumor is a negative prognostic factor in patients with HR+/HER2- mBC11

In the unadjusted meta-regression model, mutated PIK3CA was associated with an 8.4-month shorter mOS (95% CI: -13.4 to -3.5).

Meta-analysis of 3219 patients from 33 study arms across 11 randomized clinical trials of patients with HR+/HER2- mBC. Of the 3219 patients, 1386 harbored PIK3CA mutations and 1833 were wild type. Trials identified via systematic literature review. Trial arms with PI3K-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS.11

EARLY TESTING CAN HELP IDENTIFY FACTORS AFFECTING PATIENT OUTCOMES1

Early detection of mutations via NGS can empower you and your patients to make the best decisions about care—including finding appropriate treatment options.1

FDA has approved 1L+ targeted therapies* for HR+/HER2- mBC mutations, including12-14:

  • PIK3CA mutation
  • AKT1 alterations
  • PTEN alterations
  • BRCA mutation

*As of May 2024.

The number of actionable biomarkers in HR+/HER2- mBC is expanding12-16

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for mBC Biomarker Testing

NCCN GUIDELINES® RECOMMEND EARLY AND COMPREHENSIVE BIOMARKER TESTING16

NCCN Guidelines recommend the following for biomarker testing in mBC16

SELECT NCCN GUIDELINES–RECOMMENDED BIOMARKER TESTING FOR mBC16

The NCCN Guidelines for mBC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques, but do not endorse any specific commercially available biomarker assays or commercial laboratories.16
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.16
Additional breast cancer subtypes are included in NCCN Guidelines.16
Please see the latest version of the NCCN Guidelines for the most up-to-date and detailed recommendations.

NGS is a comprehensive biomarker test recommended by NCCN Guidelines to identify and detect a range of mutations, which may be actionable.4-6,16

BENEFIT AND IMPACT OF NGS TESTING

UNDERSTANDING THE BENEFIT OF COMPREHENSIVE BIOMARKER TESTING WITH NGS

You can efficiently identify certain mutations by using a broad approach, such as NGS, instead of sequential single-gene testing.16

NGS testing17

DNA sequencing and mutation detection that can sequence thousands of genes in a short period

PCR testing18

Rapid amplification of a specific DNA segment that allows detection and identification of specific gene sequences

NGS VS PCR

NGS can determine a part of the patient's genome, which may provide valuable information for treatment17

Both can rapidly produce many copies of a specific sequence of DNA17,18

PCR tests detect a limited range of mutations, which may result in false negative results for any mutations that go undetected19

α-PI3Ki=phosphoinositide 3-kinase alpha-specific inhibitor; AKTi=alpha serine/threonine-protein kinase inhibitor; BC=breast cancer; BRCA=breast cancer gene; dMMR=deficient mismatch repair; DNA=deoxyribonucleic acid; ER=estrogen receptor; ER-=estrogen receptor-negative; ER+=estrogen receptor-positive; ESR1=estrogen receptor 1; FISH=fluorescence in situ hybridization; gBRCA=germline breast cancer mutation; HER2-=human epidermal growth factor receptor-negative; HER2+=human epidermal growth factor receptor-positive; HR-=hormone receptor-negative; HR+=hormone receptor-positive; IHC= immunohistochemistry; IM=intramuscular; NTRK=neurotrophic tropomyosin kinase receptor; Mb=megabase; MSI-H=microsatellite instability biomarker-high; mut=mutation; mt=mutant; OS=overall survival; PALB2=partner and localizer of breast cancer gene 2; PARPi=poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor; PFS=progression-free survival; PIK3=phosphatidylinositol 3-kinase; PIK3CA=phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PR=progesterone receptor; PTEN=phosphatase and tensin homolog deleted on chromosome 10; RET=rearranged during transfection; RNA=ribonucleic acid; SERD=selective estrogen receptor degrader; TMB-H=tumor mutational burden-high.

References: 1. Biomarker testing for cancer treatment. National Cancer Institute. https:/​/​www.cancer.gov/​about-cancer/​treatment/​types/​biomarker-testing-cancer-treatment. Accessed May 31, 2024. 2. Henry NL, Somerfield MR, Dayao Z, et al. Biomarkers for systemic therapy in metastatic breast cancer: ASCO Guideline Update. J Clin Oncol. 2022;40(27):3205-3221. doi:10.1200/JCO.22.01063. 3. Freedman AN, Klabunde CN, Wiant K, et al. Use of next-generation sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States. JCO Precis Oncol. 2018;2:PO.18.00169. doi:10.1200/PO.18.00169. 4. Cobain EF, Wu YM, Vats P, et al. Assessment of clinical benefit of integrative genomic profiling in advanced solid tumors. JAMA Oncol. 2021;7(4):525-533. doi:10.1001/jamaoncol.2020.7987. 5. The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012;490(7418):61-70. doi:10.1038/nature11412. 6. Martinez-Saez O, Chic N, Pascual T. Frequency and spectrum of PIK3CA somatic mutations in breast cancer. Breast Cancer Res. 2020;22(1):45. doi:10.1186/s13058-020-01284-9. 7. Angus L, Smid M, Wilting SM, et al. Genomic landscape of metastatic breast cancer and its clinical implications. Nat Genet. 2019;51(10):1450-1458. doi:10.1038/s41588-019-0507-7. 8. Anderson EJ, Mollon LE, Dean JL, et al. A systematic review of the prevalence and diagnostic workup of PIK3CA mutations in HR+/HER2– metastatic breast cancer. Int J Breast Cancer. 2020:2020:3759179. doi:10.1155/2020/3759179. 9. SEER Cancer Stat Facts: Female Breast Cancer Subtypes. National Cancer Institute. https:/​/​seer.cancer.gov/​statfacts/​html/​breast-subtypes.html. Accessed March 5, 2024. 10. Chen JW, Murugesan K, Newberg JY, et al. Comparison of PIK3CA mutation prevalence in breast cancer across predicted ancestry populations. JCO Precis Oncol. 2022;6:e2200341. doi:10.1200/PO.22.00341. 11. Fillbrunn M, Signorovitch J, André F, et al. PIK3CA mutation status, progression and survival in advanced HR+/HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022;22(1):1002. doi: 10.1186/s12885-022-10078-5. 12. Piqray. Prescribing Information. Novartis Pharmaceuticals; 2024. 13. Truqap. Prescribing Information. AstraZeneca Pharmaceuticals; 2023. 14. Lynparza. Prescribing Information. AstraZeneca Pharmaceuticals; 2023. 15. Orserdu. Prescribing Information. Stemline Therapeutics; 2023. 16. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.4.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed July 11, 2024. 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 the content, use, or application of these guidelines and disclaims any responsibility for their application or use in any way. 17. NCI dictionary of genetics terms: next-generation sequencing. National Cancer Institute. https:/​/​www.cancer.gov/​publications/​dictionaries/​genetics-dictionary/​def/​next-generation-sequencing. Accessed June 4, 2024. 18. NCI dictionary of genetics terms: PCR. National Cancer Institute. https:​/​​​/​​www.cancer.gov/​​publications​/​​​dictionaries​/​​genetics-dictionary​/​​​def​/​​​pcr. Accessed June 4, 2024. 19. therascreen PIK3CA RGQ PCR Kit. Instructions for Use (Handbook). QIAGEN, 2019.

    • Biomarker testing for cancer treatment. National Cancer Institute. https:/​/​www.cancer.gov/​about-cancer/​treatment/​types/​biomarker-testing-cancer-treatment. Accessed May 31, 2024.

      Biomarker testing for cancer treatment. National Cancer Institute. https:/​/​www.cancer.gov/​about-cancer/​treatment/​types/​biomarker-testing-cancer-treatment. Accessed May 31, 2024.

    • Henry NL, Somerfield MR, Dayao Z, et al. Biomarkers for systemic therapy in metastatic breast cancer: ASCO Guideline Update. J Clin Oncol. 2022;40(27):3205-3221. doi:10.1200/JCO.22.01063.

      Henry NL, Somerfield MR, Dayao Z, et al. Biomarkers for systemic therapy in metastatic breast cancer: ASCO Guideline Update. J Clin Oncol. 2022;40(27):3205-3221. doi:10.1200/JCO.22.01063.

    • Freedman AN, Klabunde CN, Wiant K, et al. Use of next-generation sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States. JCO Precis Oncol. 2018;2:PO.18.00169. doi:10.1200/PO.18.00169.

      Freedman AN, Klabunde CN, Wiant K, et al. Use of next-generation sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States. JCO Precis Oncol. 2018;2:PO.18.00169. doi:10.1200/PO.18.00169.

    • Cobain EF, Wu YM, Vats P, et al. Assessment of clinical benefit of integrative genomic profiling in advanced solid tumors. JAMA Oncol. 2021;7(4):525-533. doi:10.1001/jamaoncol.2020.7987.

      Cobain EF, Wu YM, Vats P, et al. Assessment of clinical benefit of integrative genomic profiling in advanced solid tumors. JAMA Oncol. 2021;7(4):525-533. doi:10.1001/jamaoncol.2020.7987.

    • The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012;490(7418):61-70. doi:10.1038/nature11412.

      The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012;490(7418):61-70. doi:10.1038/nature11412.

    • Martinez-Saez O, Chic N, Pascual T. Frequency and spectrum of PIK3CA somatic mutations in breast cancer. Breast Cancer Res. 2020;22(1):45. doi:10.1186/s13058-020-01284-9.

      Martinez-Saez O, Chic N, Pascual T. Frequency and spectrum of PIK3CA somatic mutations in breast cancer. Breast Cancer Res. 2020;22(1):45. doi:10.1186/s13058-020-01284-9.

    • Angus L, Smid M, Wilting SM, et al. Genomic landscape of metastatic breast cancer and its clinical implications. Nat Genet. 2019;51(10):1450-1458. doi:10.1038/s41588-019-0507-7.

      Angus L, Smid M, Wilting SM, et al. Genomic landscape of metastatic breast cancer and its clinical implications. Nat Genet. 2019;51(10):1450-1458. doi:10.1038/s41588-019-0507-7.

    • Anderson EJ, Mollon LE, Dean JL, et al. A systematic review of the prevalence and diagnostic workup of PIK3CA mutations in HR+/HER2– metastatic breast cancer. Int J Breast Cancer. 2020:2020:3759179. doi:10.1155/2020/3759179.

      Anderson EJ, Mollon LE, Dean JL, et al. A systematic review of the prevalence and diagnostic workup of PIK3CA mutations in HR+/HER2– metastatic breast cancer. Int J Breast Cancer. 2020:2020:3759179. doi:10.1155/2020/3759179.

    • SEER Cancer Stat Facts: Female Breast Cancer Subtypes. National Cancer Institute. https:/​/​seer.cancer.gov/​statfacts/​html/​breast-subtypes.html. Accessed March 5, 2024.

      SEER Cancer Stat Facts: Female Breast Cancer Subtypes. National Cancer Institute. https:/​/​seer.cancer.gov/​statfacts/​html/​breast-subtypes.html. Accessed March 5, 2024.

    • Chen JW, Murugesan K, Newberg JY, et al. Comparison of PIK3CA mutation prevalence in breast cancer across predicted ancestry populations. JCO Precis Oncol. 2022;6:e2200341. doi:10.1200/PO.22.00341.

      Chen JW, Murugesan K, Newberg JY, et al. Comparison of PIK3CA mutation prevalence in breast cancer across predicted ancestry populations. JCO Precis Oncol. 2022;6:e2200341. doi:10.1200/PO.22.00341.

    • Fillbrunn M, Signorovitch J, André F, et al. PIK3CA mutation status, progression and survival in advanced HR+/HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022;22(1):1002. doi: 10.1186/s12885-022-10078-5.

      Fillbrunn M, Signorovitch J, André F, et al. PIK3CA mutation status, progression and survival in advanced HR+/HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022;22(1):1002. doi: 10.1186/s12885-022-10078-5.

    • Piqray. Prescribing Information. Novartis Pharmaceuticals; 2024.

      Piqray. Prescribing Information. Novartis Pharmaceuticals; 2024.

    • Truqap. Prescribing Information. AstraZeneca Pharmaceuticals; 2023.

      Truqap. Prescribing Information. AstraZeneca Pharmaceuticals; 2023.

    • Lynparza. Prescribing Information. AstraZeneca Pharmaceuticals; 2023.

      Lynparza. Prescribing Information. AstraZeneca Pharmaceuticals; 2023.

    • Orserdu. Prescribing Information. Stemline Therapeutics; 2023.

      Orserdu. Prescribing Information. Stemline Therapeutics; 2023.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.4.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed July 11, 2024. 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 the content, use, or application of these guidelines and disclaims any responsibility for their application or use in any way.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.4.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed July 11, 2024. 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 the content, use, or application of these guidelines and disclaims any responsibility for their application or use in any way.

    • NCI dictionary of genetics terms: next-generation sequencing. National Cancer Institute. https:/​/​www.cancer.gov/​publications/​dictionaries/​genetics-dictionary/​def/​next-generation-sequencing. Accessed June 4, 2024.

      NCI dictionary of genetics terms: next-generation sequencing. National Cancer Institute. https:/​/​www.cancer.gov/​publications/​dictionaries/​genetics-dictionary/​def/​next-generation-sequencing. Accessed June 4, 2024.

    • NCI dictionary of genetics terms: PCR. National Cancer Institute. https:/​/​www.cancer.gov/​publications/​dictionaries/​genetics-dictionary/​def/​pcr. Accessed June 4, 2024.

      NCI dictionary of genetics terms: PCR. National Cancer Institute. https:/​/​www.cancer.gov/​publications/​dictionaries/​genetics-dictionary/​def/​pcr. Accessed June 4, 2024.

    • therascreen PIK3CA RGQ PCR Kit. Instructions for Use (Handbook). QIAGEN, 2019.

      therascreen PIK3CA RGQ PCR Kit. Instructions for Use (Handbook). QIAGEN, 2019.