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Erschienen in: Clinical and Translational Oncology 8/2018

01.02.2018 | Research Article

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

verfasst von: Z. Liu, W. Liu

Erschienen in: Clinical and Translational Oncology | Ausgabe 8/2018

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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.
Literatur
1.
2.
Zurück zum Zitat 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.CrossRef 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.CrossRef
5.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
7.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat 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.CrossRef 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.CrossRef
9.
Zurück zum Zitat 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. 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.
10.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
11.
12.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat 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.CrossRefPubMedCentral 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.CrossRefPubMedCentral
14.
15.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
17.
18.
Zurück zum Zitat 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.CrossRef 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.CrossRef
19.
Zurück zum Zitat Ma CX. The PI3K pathway as a therapeutic target in breast cancer. Am J Hematol Oncol®. 2015;11(3):23–29. Ma CX. The PI3K pathway as a therapeutic target in breast cancer. Am J Hematol Oncol®. 2015;11(3):23–29.
20.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Singletary SE, Greene FL, editors. Revision of breast cancer staging: the 6th edition of the TNM classification 2003: Wiley Online Library. Singletary SE, Greene FL, editors. Revision of breast cancer staging: the 6th edition of the TNM classification 2003: Wiley Online Library.
22.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
23.
Zurück zum Zitat Brinkmann B, Rand S, Bajanowski T. Forensic identification of urine samples. Int J Legal Med. 1992;105(1):59–61.CrossRefPubMed Brinkmann B, Rand S, Bajanowski T. Forensic identification of urine samples. Int J Legal Med. 1992;105(1):59–61.CrossRefPubMed
24.
Zurück zum Zitat 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.PubMed 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.PubMed
25.
Zurück zum Zitat 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.CrossRef 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.CrossRef
26.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
27.
Zurück zum Zitat 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.CrossRef 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.CrossRef
28.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
29.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
Metadaten
Titel
Association of urinary and plasma DNA in early breast cancer patients and its links to disease relapse
verfasst von
Z. Liu
W. Liu
Publikationsdatum
01.02.2018
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 8/2018
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-017-1825-9

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