Towards personalized cancer care: liquid biopsy for monitoring primary breast cancer

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Breast cancer is the most common cancer in women, accounting for 23% of all cancer diagnoses (1). At the time of diagnosis, a majority of patients (>90%) will have localized disease, which is typically treated with surgery, radiation and therapeutic agents. Localized disease is associated with improved five-year survival rates, relative to more advanced cancers – making early detection and treatment an important factor in patient outcomes (2). One of the current challenges in breast cancer care is determining which patients with primary (localized) breast cancer are at risk for disease progression and metastatic spread. Although the risk of metastatic spread is greatest within the first two years following diagnosis of primary breast cancer, approximately half of recurrences occur more than five years after surgery (3). During this period of remission, liquid biopsy for circulating nucleic acids would provide a minimally invasive method for detecting disease progression before it becomes clinically apparent. In this post, we explore the use of liquid biopsy to evaluate patients with primary breast cancer.

In one prospective study, the CellSearch system was used to examine whether CTCs at diagnosis were associated with poor disease-free survival and overall survival (4). Peripheral blood (30 ml) was collected from 602 patients undergoing surgery for breast cancer. A total of 404 patients were classified as having stage I through stage III breast cancer and were included in the analysis. Patient prognosis was designated as either favorable (CTC = 0) or unfavorable (≥1 CTC). A total of 328 patients had no CTCs, and 11.6% of these patients experienced disease recurrence. Among patients with ≥1 CTC, a larger percentage (21.1%) experienced disease recurrence. Breast cancer-related death occurred in 14.5% of patients with ≥1 CTC, and in 4.3% of patients with CTC = 0 (p = 0.001). The study indicates that patients undergoing surgery with CTCs are associated with an increased risk of cancer-related mortality.

Another recent study highlighted the utility of ctDNA for predicting the risk of relapse (5). ctDNA was analyzed in 55 primary breast cancer patients who had received neoadjuvant chemotherapy. ctDNA was initially obtained before treatment and was subsequently collected at multiple time points after surgery. In 80% of patients with disease relapse, ctDNA was detected in at least one sample post-surgery. Prediction of relapse based on the presence of ctDNA occurred at a median time point of 7.9 months before clinical detection of relapse using radiographic imaging. The study demonstrates the validity of ctDNA for predicting residual disease in patients – and at a significantly earlier time point for detection.

The use of liquid biopsy in patients with primary breast cancer is promising for several reasons. Early detection of metastasis would allow for changes in treatment strategy before the disease progression becomes clinically apparent. Monitoring for emerging mutations informs treatment strategies with targeted therapeutics. Finally, predicting when patients are at risk for relapse may prevent unnecessary treatment in low-risk patients – a tactic that many new technologies are increasingly using. QIAGEN’s liquid biopsy solutions empower you to rapidly analyze circulating nucleic acids, taking you to the first step towards uncovering valuable biomarkers in your samples.

Learn more about QIAGEN’s tools for liquid biopsy research at our online resource center.

 

References

1. Abraham, J., Gulley, J.L., and Allegra, C.J. (2014) Bethesda Handbook of Clinical Oncology. 4th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health.
2. National Cancer Institute. (Link)
3. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365, 1687–717. (Link)
4. Franken, B., et al. (2012) Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer. Breast Cancer Res.14, R133. (Link)
5. Garcia-Murillas, I., et al. (2015) Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 7, 302ra133. (Link)

Wei Cao, Ph.D.

Senior Global Marketing Manager, Translational Sciences

Dr. Wei Cao joined QIAGEN in 2010 and currently leads the webinar program, presenting various topics on advanced techniques in biomedical research. She received her Ph.D. from Peking University in China in 2010, and conducted postdoctoral research at Weill Cornell Medical College in New York City. Before joining QIAGEN, Dr. Cao worked as a senior scientist in R&D in pharmaceutical and biotech, focusing on HIV, HCV and cancer drug discovery and development.

Yumin Zhang

Wei,

Although I am working directly in this field, I am interested in the emerging techniques. (I am working in PET molecular imaging for drug development.). Yumin

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