Advertisement

Clinical and Translational Oncology

, Volume 20, Issue 8, pp 1053–1060 | Cite as

Association of urinary and plasma DNA in early breast cancer patients and its links to disease relapse

  • Z. Liu
  • W. Liu
Research Article

Abstract

Purpose

Identifying patients who are at risk of relapse is a key challenge of primary breast cancer. The current study investigates the utility of urinary DNA in breast cancer management and as a predictor of relapse. This work also compares the sensitivity of plasma DNA with urinary DNA.

Methods

Blood plasma and urine specimens were collected concurrently from 200 breast cancer patients receiving neoadjuvant chemotherapy. Comparison of both plasma and urinary DNA was performed at baseline to determine assay significance. Serial measurements of urinary DNA were conducted to gauge DNA variations after surgery. Correlations to disease relapse were performed to affirm the clinical utility of urinary DNA.

Results

Molecular analysis showed patients were successfully identified with mutant PIK3CA using urinary DNA. A strong correlation was affirmed from urinary and plasma DNA at baseline with the correlation coefficient r = 0.859. We analyzed post-surgery measurements of urinary DNA for disease-relapse predictions. In subsequent serial followup of urinary DNA samples, we confirmed increased sensitivity in predicting relapse of these patients. The hazard ratio determined at the 9-month was 1.51 that identified patients at greater risk of disease relapse.

Conclusion

Urinary DNA offers a unique opportunity to glimpse upon dynamic changes in early breast cancer. Our results demonstrated good correlation to plasma DNA and post monitoring of cancer patients to identify individuals susceptible to a high risk of relapse. This potentially allows for early intervention such as adjuvant chemotherapy to be administered to better manage these patients.

Keywords

Breast cancer Urinary DNA Plasma DNA ctDNA Relapse prediction 

Notes

Acknowledgements

This work was supported by research grants provided by Jingzhou First People’s Hospital.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

All human and animal studies have been approved by the appropriate ethics committee and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LAG et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. JNCI. 2014;106(5):dju55.CrossRefGoogle Scholar
  3. 3.
    Brackstone M, Townson JL, Chambers AF. Tumour dormancy in breast cancer: an update. Breast Cancer Res. 2007;9(3):208.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32(6):579–86.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Niekel MC, Bipat S, Stoker J. Diagnostic imaging of colorectal liver metastases with CT, MR imaging, FDG PET, and/or FDG PET/CT: a meta-analysis of prospective studies including patients who have not previously undergone treatment. Radiology. 2010;257(3):674–84.CrossRefPubMedGoogle Scholar
  6. 6.
    Weissleder R, Pittet MJ. Imaging in the era of molecular oncology. Nature. 2008;452(7187):580.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early-and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;2004(351):781–91.CrossRefGoogle Scholar
  9. 9.
    Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch R-D, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Can Res. 2001;61(4):1659–65.Google Scholar
  10. 10.
    Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10(20):6897–904.CrossRefPubMedGoogle Scholar
  11. 11.
    Maheswaran S, Haber DA. Circulating tumor cells: a window into cancer biology and metastasis. Curr Opin Genet Dev. 2010;20(1):96–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Li J, Gregory SG, Garcia-Blanco MA, Armstrong AJ. Using circulating tumor cells to inform on prostate cancer biology and clinical utility. Crit Rev Clin Lab Sci. 2015;52(4):191–210.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Krishnamurthy N, Spencer E, Torkamani A, Nicholson L. Liquid biopsies for cancer: coming to a patient near you. J Clin Med. 2017;6(1):3.CrossRefPubMedCentralGoogle Scholar
  14. 14.
    Smerage JB, Hayes DF. The measurement and therapeutic implications of circulating tumour cells in breast cancer. Br J Cancer. 2006;94(1):8.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Olsson E, Winter C, George A, Chen Y, Howlin J, Tang MHE, et al. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol Med. 2015;7(8):1034–47.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450(7173):1235–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer. Nat Rev Drug Discov. 2009;8(8):627.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Cidado J, Park BH. Targeting the PI3K/Akt/mTOR pathway for breast cancer therapy. J Mammary Gland Biol Neoplas. 2012;17(3–4):205–16.CrossRefGoogle Scholar
  19. 19.
    Ma CX. The PI3K pathway as a therapeutic target in breast cancer. Am J Hematol Oncol®. 2015;11(3):23–29.Google Scholar
  20. 20.
    Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, Inao T, Sueta A, Fujiwara S, et al. Prognostic role of PIK3CA mutations of cell-free DNA in early-stage triple negative breast cancer. Cancer Sci. 2015;106(11):1582–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Singletary SE, Greene FL, editors. Revision of breast cancer staging: the 6th edition of the TNM classification 2003: Wiley Online Library.Google Scholar
  22. 22.
    Yokota M, Tatsumi N, Tsuda I, Takubo T, Hiyoshi M. DNA extraction from human urinary sediment. J Clin Lab Anal. 1998;12(2):88–91.CrossRefPubMedGoogle Scholar
  23. 23.
    Brinkmann B, Rand S, Bajanowski T. Forensic identification of urine samples. Int J Legal Med. 1992;105(1):59–61.CrossRefPubMedGoogle Scholar
  24. 24.
    Botezatu I, Og Serdyuk, Potapova G, Shelepov V, Alechina R, Molyaka Y, et al. Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism. Clin Chem. 2000;46(8):1078–84.PubMedGoogle Scholar
  25. 25.
    Reckamp KL, Melnikova VO, Karlovich C, Sequist LV, Camidge DR, Wakelee H, et al. A highly sensitive and quantitative test platform for detection of NSCLC EGFR mutations in urine and plasma. J Thoracic Oncol. 2016;11(10):1690–700.CrossRefGoogle Scholar
  26. 26.
    Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015;7(302):302ra133.CrossRefPubMedGoogle Scholar
  27. 27.
    Tachtsidis A, McInnes LM, Jacobsen N, Thompson EW, Saunders CM. Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells. Clin Exp Metas. 2016;33(6):521–50.CrossRefGoogle Scholar
  28. 28.
    Guttery DS, Blighe K, Page K, Marchese SD, Hills A, Coombes RC, et al. Hide and seek: tell-tale signs of breast cancer lurking in the blood. Cancer Metastasis Rev. 2013;32(1–2):289–302.CrossRefPubMedGoogle Scholar
  29. 29.
    Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–90.CrossRefPubMedGoogle Scholar
  30. 30.
    Gedvilaitė V, Schveigert D, Cicėnas S. Cell-free DNA in non-small cell lung cancer. Acta medica Lituanica. 2017;24(2):138.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Department of OncologyJingzhou First People’s HospitalJingzhouChina
  2. 2.Faculty of MedicineYangtze UniversityJingzhouChina

Personalised recommendations