Serial ctDNA Detection Shows Promise for Predicting Breast Cancer Recurrence

Longitudinal monitoring of circulating tumour DNA could serve as predictor of relapse in breast cancer patients undergoing neoadjuvant chemotherapy and surgery

medwireNews: The presence of circulating tumour DNA (ctDNA) in plasma samples obtained at multiple timepoints during treatment and follow-up from women with localised breast cancer could inform the risk of early relapse, suggests a preliminary study.

Among 55 women with early, nonmetastatic breast cancer treated with neoadjuvant chemotherapy and surgical resection, the pretreatment biopsy samples of 43 harboured at least one somatic mutation in a panel of 14 breast cancer-associated genes. The authors used these mutations to design an individualised digital Polymerase chain reaction assay to detect ctDNA – only detectable if it contains Mutations, they explain – in plasma samples collected at baseline, 2 to 4 weeks after surgery and at 6-month intervals during follow-up.

Although ctDNA was present in 69% of 42 evaluable baseline samples, its presence did not predict breast cancer recurrence during a median 21.4 months of follow-up. But disease-free survival was significantly shorter for the seven (19%) women with ctDNA detected in the postoperative sample than for the 30 who tested negative for ctDNA, at a median of 6.5 months versus not reached (hazard ratio [HR]=25.1).

Moreover, detection of ctDNA in longitudinal samples also served as a significant predictor of relapse, with median disease-free survival times of 13.6 months for the 13 patients with ctDNA in at least one serial sample and not reached for the 30 patients without ctDNA in serial samples (HR=12.0).

Among the 15 women who relapsed during follow-up, ctDNA was detected in 50% of the postsurgical samples (n=12) and in 80% of longitudinally collected samples. Only one patient with detectable ctDNA after surgery and during follow-up did not relapse.

Lead investigator Nicholas Turner, from The Institute of Cancer Research in London, UK, and colleagues note, however, that ctDNA was not detected in either the postsurgical or longitudinal samples of the three patients who had an intracranial metastatic relapse, suggesting that the use of so-called mutation tracking may be “challenging” for certain sites of disease relapse.

ctDNA detection preceded clinical relapse by a median of 7.9 months, the team reports in Science Translational Medicine, which commentators Tilak Sundaresan and Daniel Haber, both from Harvard Medical School in Boston, Massachusetts, USA, say in a linked piece defines “a period of opportunity in which additional therapeutic interventions might suppress recurrence”.

Although enthusiastic about the findings, the commentators say that further research will be needed to evaluate the feasibility of ctDNA detection in women with clinically defined low-risk primary cancer and assess its efficacy in predicting late relapse.

References

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. doi:10.1126/scitranslmed.aab0021

Sundaresan TK, Haber DA. Does molecular monitoring matter in early-stage breast cancer? Sci Transl Med 2015; 7: 302fs35. doi:10.1126/scitranslmed.aac9445

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