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Tracking of mutations in circulating tumour DNA to monitor relapse in breast cancer

Purpose and aims

The overall purpose is to improve sensitivity of circulating tumour DNA (ctDNA) analysis to enable detection of minimal residual disease (MRD) or early relapse in breast cancer using IBSAFE digital droplet PCR (ddPCR). The specific goals include designing ddPCR assays for each patient based on the mutations called in tissue biopsy samples, detecting of mutations in ctDNA even when present at extremely low frequencies during or after neoadjuvant treatment and after surgery in a large patient cohort. We aim to validate the use of this technique on ctDNA as a predictive biomarker to guide subsequent adjuvant therapy timely and effectively, and to avoid overtreatment.


Breast cancer has been estimated as the most commonly diagnosed cancer and the fifth most common cause of cancer deaths worldwide in 2020 [1]. The majority of breast cancer patients are diagnosed at early stage without macroscopic evidence of metastases. Neoadjuvant systemic therapy has been developed as a systematic approach before definitive surgery in patients with early and locally advanced breast cancer to improve outcomes of subsequent treatment. However, micrometastatic disease or MRD might persist and result in recurrent disease after neoadjuvant treatment and surgery. Surveillance of micrometastatic disease or MRD could be used in the setting of a clinical trial to guide adjuvant therapy of patients with high risk of disease recurrence. However, this has been a main challenge with current technologies [2].

Liquid biopsies including ctDNA have gained interest as a minimal invasive approach compared with tissue biopsies to monitoring therapeutic response and presence of residual disease after surgery. The main approaches to identify ctDNA mutations are ddPCR and targeted next generation sequencing (NGS). However, most current approaches are not able to reliably detect ctDNA at a very low level in plasma cell free DNA (cfDNA) after completive treatment in non-metastatic cancer patients. Optimised methods have been proposed to improve sensitivity of ctDNA detection [2-4], but there are limitations including relatively small study cohort (mostly less than 60 patients enrolled), short follow-up time and lack of standardized protocols for clinical implementation. Clinical applications of ctDNA to detect micrometastatic disease or MRD in breast cancer still awaits further studies. From my perspective, sex and gender perspectives are not relevant within the field/area the project relates to.

Significance and scientific novelty

Several studies reported the possibility to monitor MRD in breast cancer by tracking ctDNA in plasma [2-4]. Despite encouraging findings in these studies, additional studies are required to overcome the above mentioned limitations. We will apply the ultrasensitive IBSAFE ddPCR method on a cohort of 171 patients with an follow-up up to 6 years to detect ctDNA mutations.


  1. H. Sung, J. Ferlay, R.L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, F. Bray, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA: a cancer journal for clinicians 71(3) (2021) 209-249.
  2. B.R. McDonald, T. Contente-Cuomo, S.J. Sammut, A. Odenheimer-Bergman, B. Ernst, N. Perdigones, S.F. Chin, M. Farooq, R. Mejia, P.A. Cronin, K.S. Anderson, H.E. Kosiorek, D.W. Northfelt, A.E. McCullough, B.K. Patel, J.N. Weitzel, T.P. Slavin, C. Caldas, B.A. Pockaj, M. Murtaza, Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer, Science translational medicine 11(504) (2019).
  3. J. Moss, A. Zick, A. Grinshpun, E. Carmon, M. Maoz, B.L. Ochana, O. Abraham, O. Arieli, L. Germansky, K. Meir, B. Glaser, R. Shemer, B. Uziely, Y. Dor, Circulating breast-derived DNA allows universal detection and monitoring of localized breast cancer, Annals of oncology : official journal of the European Society for Medical Oncology 31(3) (2020) 395-403.
  4. I. Garcia-Murillas, G. Schiavon, B. Weigelt, C. Ng, S. Hrebien, R.J. Cutts, M. Cheang, P. Osin, A. Nerurkar, I. Kozarewa, J.A. Garrido, M. Dowsett, J.S. Reis-Filho, I.E. Smith, N.C. Turner, Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer, Science translational medicine 7(302) (2015) 302ra133.
Pei Meng. Portrait.

Pei Meng

CanFaster postdoc

Lao Saal. Portrait.

Lao Saal

+46 46 222 03 65

Department of Clinical Sciences
Section V - Oncology and Pathology
Medicon Village, Building 404
Scheelevägen 2; 223 81 Lund

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