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What’s New Liquid Biopsy – PIK3CA-Testung beim Mammakarzinom

What’s new liquid biopsy—PIK3CA testing in breast cancer

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Zusammenfassung

Der Einsatz von Liquid Biopsies zur Untersuchung von molekularen Veränderungen an zirkulierender Tumor DNA (ctDNA) für die Companion-Diagnostik hat in den letzten Jahren an Bedeutung gewonnen. PIK3CA zählt zu den am häufigsten mutierten Genen in Brustkrebspatientinnen. Die auch in Europa erwartete Zulassung des PIK3CA-Inhibitors Alpelisib mittels Liquid Biopsies infolge der Ergebnisse der SOLAR1-Studie ist daher eine vielversprechende Möglichkeit, dass mehr Brustkrebspatientinnen von einer zielgerichteten Therapie profitieren können. Es ist demnach anzunehmen, dass es eine Erstattung für die PIK3CA-Mutationstestung auf Basis von Liquid Biopsies geben wird.

Die Auswahl eines geeigneten Testverfahrens für den Nachweis der aktivierenden PIK3CA-Mutationen sollte Faktoren wie Sensitivität, Spezifität und Detektionslimit miteinbeziehen, wobei mindestens die Kriterien des Tests aus der Zulassungsstudie erfüllt werden sollten.

Der PIK3CA-Mutationsnachweis mittels Liquid Biopsy kann dann, bei wohlüberlegtem Einsatz, eine sinnvolle Ergänzung in der molekularpathologischen Diagnostik an Gewebe sein.

Abstract

The impact of liquid biopsies on the analysis of molecular alterations of circulating tumor DNA (ctDNA) has recently increased. PIK3CA is one of the most frequently mutated genes in breast cancer and the expected approval of targeted PIK3CA therapy based on the results of the SOLAR1 trial is likely to lead to the use of liquid biopsies as another promising testing strategy in breast cancer patients who can benefit from a targeted therapy.

Choosing an appropriate method for the detection of activating PIK3CA mutations should include factors like sensitivity, specificity, and limit of detection. The test should at least meet the parameters of the assay used in the drug approval study.

If carefully used, PIK3CA mutation detection with liquid biopsies can then be a useful addition to standard tissue diagnostics.

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Literatur

  1. Mandel P, Metais P (1948) C R Seances Soc Biol Fil 142(3–4):241–243

    CAS  PubMed  Google Scholar 

  2. Lo YM et al (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350(9076):485–487

    Article  CAS  Google Scholar 

  3. Bettegowda C et al (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6(224):224ra24

    Article  Google Scholar 

  4. Vollbrecht C (2020) Liquid Biopsy – Erweiterung des molekularpathologischen Spektrums. Best Pract Onkol 15(6):230–238. https://doi.org/10.1007/s11654-020-00222-7

    Article  Google Scholar 

  5. Dawson SJ et al (2013) Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368(13):1199–1209

    Article  CAS  Google Scholar 

  6. Diehl F et al (2005) Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci U S A 102(45):16368–16373

    Article  CAS  Google Scholar 

  7. Garcia-Murillas I et al (2015) Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med 7(302):302ra133

    Article  Google Scholar 

  8. Ma F et al (2016) ctDNA dynamics: a novel indicator to track resistance in metastatic breast cancer treated with anti-HER2 therapy. Oncotarget 7(40):66020–66031

    Article  Google Scholar 

  9. Griesinger F et al (2020) Onkopedia. Lungenkarzinom, nicht-kleinzellig (NSCLC). https://www.onkopedia.com/. Zugegriffen: 19. Nov. 2020

  10. Di Leo A et al (2018) Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 19(1):87–100

    Article  Google Scholar 

  11. Chandarlapaty S et al (2016) Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO‑2 clinical trial. JAMA Oncol 2(10):1310–1315

    Article  Google Scholar 

  12. Smith RA et al (2018) Cancer screening in the United States, 2018: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin 68(4):297–316

    Article  Google Scholar 

  13. Rosenbaum JN, Weisman P (2017) The evolving role of companion diagnostics for breast cancer in an era of next-generation Omics. Am J Pathol 187(10):2185–2198

    Article  CAS  Google Scholar 

  14. Howlader N et al (2014) US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. https://doi.org/10.1093/jnci/dju055

    Article  PubMed  PubMed Central  Google Scholar 

  15. Setiawan VW et al (2009) Breast cancer risk factors defined by estrogen and progesterone receptor status: the multiethnic cohort study. Am J Epidemiol 169(10):1251–1259

    Article  Google Scholar 

  16. Cancer Genome Atlas, N (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70

    Article  Google Scholar 

  17. Goncalves MD, Hopkins BD, Cantley LC (2018) Phosphatidylinositol 3‑Kinase, growth disorders, and cancer. N Engl J Med 379(21):2052–2062

    Article  CAS  Google Scholar 

  18. Janku F (2017) Phosphoinositide 3‑kinase (PI3K) pathway inhibitors in solid tumors: from laboratory to patients. Cancer Treat Rev 59:93–101

    Article  CAS  Google Scholar 

  19. Gymnopoulos M, Elsliger MA, Vogt PK (2007) Rare cancer-specific mutations in PIK3CA show gain of function. Proc Natl Acad Sci U S A 104(13):5569–5574

    Article  CAS  Google Scholar 

  20. Bader AG et al (2005) Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer 5(12):921–929

    Article  CAS  Google Scholar 

  21. Gao J et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6(269):pl1

    Article  Google Scholar 

  22. Cerami E et al (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2(5):401–404

    Article  Google Scholar 

  23. Andre F et al (2019) Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med 380(20):1929–1940

    Article  CAS  Google Scholar 

  24. QIAGEN (2019) therascreen® PIK3CA RGQ PCR Kit Instructions for Use (Handbook). Version 1 Document HB-2614-001 QIAGEN GmbH, QIAGEN Strasse 1, 40724 Hilden, Germany

    Google Scholar 

  25. Jennings LJ et al (2017) Guidelines for validation of next-generation sequencing-based oncology panels: a joint consensus recommendation of the association for molecular pathology and college of American pathologists. J Mol Diagn 19(3):341–365

    Article  Google Scholar 

  26. Underhill HR et al (2016) Fragment length of circulating tumor DNA. PLoS Genet 12(7):e1006162

    Article  Google Scholar 

  27. Vora SR et al (2014) CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors. Cancer Cell 26(1):136–149

    Article  CAS  Google Scholar 

  28. Juric D et al (2015) Convergent loss of PTEN leads to clinical resistance to a PI(3)Kalpha inhibitor. Nature 518(7538):240–244

    Article  CAS  Google Scholar 

  29. Baretton G et al (2020) Positionspapier – Testung in der Onkologie. Pathologe. https://www.pathologie-dgp.de/media/Dgp/Presse/Molekulare_Diagnostik_Positionspapier_2019.1_final.pdf. https://www.pathologie-dgp.de/die-dgp/aktuelles/meldung/positionspapier-testung-in-der-onkologie/

  30. Fasching PA et al (2015) Biomarkers in patients with metastatic breast cancer and the PRAEGNANT study network. Geburtshilfe Frauenheilkd 75(1):41–50

    Article  CAS  Google Scholar 

  31. Pantel K (2020) European Liquid Biopy Society (ELBS). https://www.uke.de/english/departments-institutes/institutes/tumor-biology/european-liquid-biopsy-society-elbs/index.html. Zugegriffen: 15. Okt 2020

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  1. Institut für Pathologie, Molekularpathologie, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland

    Claudia Vollbrecht

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Correspondence to Claudia Vollbrecht.

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C. Vollbrecht gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden vom Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Vollbrecht, C. What’s New Liquid Biopsy – PIK3CA-Testung beim Mammakarzinom. Pathologe 41 (Suppl 2), 138–142 (2020). https://doi.org/10.1007/s00292-020-00868-8

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