Have a Look Around: breast cancer relapse may be printed in the blood

  • Date: 16 Sep 2015
  • Author: Leticia De Mattos-Arruda
  • Affiliation: Cancer Research UK-Cambridge Institute, Cambridge, UK - Vall d’Hebron Institute of Oncology, Barcelona, Spain
  • Link: Read the original article
  • Topic: Breast cancer
Leticia De Mattos Arruda

Recent progresses of massively parallel sequencing and digital genomic techniques support cell-free circulating tumour DNA (ctDNA) as a ‘liquid biopsy’ in cancers. In breast cancer patients, ctDNA from plasma has been investigated as a minimally invasive surrogate for tumour tissue biopsies as it can be robustly obtained from blood samples1,2.

In metastatic breast cancers, ctDNA detected in plasma has been used to non-invasively scan tumour genomes and quantify tumour burden3,4. The clinical applications for ctDNA in plasma consist of identifying actionable genomic alterations for patient stratification, monitoring of treatment responses, revealing therapeutic resistance, and detecting disease progression before clinical and radiologic confirmation3,5. In addition, ctDNA may decode tumour heterogeneity providing genomic information to tailor the therapeutic management of patients6,7.

In patients with non-metastatic breast cancers, these liquid biopsies have the potential to capture and monitor minimal residual disease following curative resection, preceding the development of clinical or radiologic recurrence8,9.

In the present article published recently at the Science Translational Medicine Journal, Garcia-Murillas et al.8 sampled a prospective cohort of 55 patients with early breast cancers, which was treated with neoadjuvant chemotherapy and surgery. The study demonstrated that the sequential monitoring of plasma DNA using tumour-specific digital PCR assays could predict relapse for early-stage breast cancer patients. In this study, the longitudinal tracking of somatic mutations present in plasma ctDNA anticipated the diagnosis of clinical metastatic relapse (average of 8 months). The identification of the genomic events of metastatic relapse through plasma-derived ctDNA showed some differences from those of the primary breast cancers, and this can preclude the effectiveness of adjuvant therapies.

The authors defined tumour-specific somatic mutations in post-surgery plasma DNA samples and characterised this minimal residual disease (that escaped standard therapy effectiveness) using targeted capture massively parallel sequencing analyses. In addition to identifying patients with higher risk of relapse, these analyses revealed potentiallytargetable biomarkers that could create opportunities for modulating systemic therapeutic interventions before the development of clinical metastasis.

It seems that one possibility to start beating cancer is to look at patients’ blood samples. This can uncover the genomic make-up of tumours and create opportunities to deal with recurrences before they arise.

Questions:

  • Would the results of this study be applicable for patients with very low tumour burden (such as stage I and II breast cancers?)
  • The longitudinal tracking of somatic mutations was shown to predict metastatic relapse. To which extend this could change the current clinical paradigms?

References:

  1. De Mattos-Arruda L, Cortes J, Santarpia L et al. Circulating tumour cells and cell-free DNA as tools for managing breast cancer. Nat Rev Clin Oncol 2013; 10: 377-389.
  2. Diaz LA, Jr., Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 2014; 32: 579-586.
  3. Dawson SJ, Tsui DW, Murtaza M et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 2013; 368: 1199-1209.
  4. Murtaza M, Dawson SJ, Tsui DW et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013; 497: 108-112.
  5. Bettegowda C, Sausen M, Leary RJ et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 2014; 6: 224ra224.
  6. Aparicio S, Caldas C. The implications of clonal genome evolution for cancer medicine. N Engl J Med 2013; 368: 842-851.
  7. De Mattos-Arruda L, Weigelt B, Cortes J et al. Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle. Ann Oncol 2014; 25: 1729-1735.
  8. Garcia-Murillas I, Schiavon G, Weigelt B et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med 2015; 7: 302ra133.
  9. Olsson E, Winter C, George A et al. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol Med 2015.

Dr. De Mattos-Arruda declares no conflict of interests.

The content of this article reflects the personal opinion of the author and is not necessarily the official position of the European Society for Medical Oncology.

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