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

Clin Transl Oncol. 2018 Aug;20(8):1053-1060. doi: 10.1007/s12094-017-1825-9. Epub 2018 Feb 1.

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; Plasma DNA; Relapse prediction; Urinary DNA; ctDNA.

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / blood
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Breast Neoplasms / urine
  • Case-Control Studies
  • DNA, Neoplasm / blood*
  • DNA, Neoplasm / urine*
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / therapy
  • Neoplasm Recurrence, Local / urine
  • Prognosis
  • Prospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm