Study: New research may lead to a blood test that detects breast cancer recurrence earlier

IN DEPTH 

Study background:

About 95% of women diagnosed with breast cancer have early-stage breast cancer with no evidence of metastasis. However, some of these women have micrometastatic disease, a form of metastasis in which breast cancer cells have spread, but newly formed tumors are too small to be detected by current imaging and testing technologies. Treatment and surgery do not always eliminate these micrometastatic lesions, and currently, we are unable to determine which patients still have micrometastatic disease (also called minimal residual disease-MRD) and which do not. Circulating tumor DNA (ctDNA) is released into the blood by dying tumor cells. ctDNA are small pieces of tumor DNA that characterize the genetic features of tumors in patients with advanced cancer. However, little data is available regarding detection of ctDNA in early-stage breast cancers to predict if they are likely to recur. 

Researchers of this study wanted to know:

Whether looking for circulating tumor DNA (ctDNA) in the blood can identify patients with micrometastatic disease. 

Population(s) looked at in the study:

The study followed 55 early-stage breast cancer patients for about 2 years. 

• None of the patients had metastatic disease at diagnosis that was detectable by standard methods.
• All of the patients received chemotherapy followed by surgery (i.e. neoadjuvant therapy).

Study findings: 

1. 15 of the 55 study patients (27%) relapsed.
2. The amount of circulating tumor DNA (ctDNA) present before treatment was not associated with early cancer recurrence.
3. In about half of patients who recurred (6 of 12 patients tested), ctDNA was detected in a blood sample taken 2-4 weeks after surgery.  Sequential blood samples taken after the post-surgery sample found ctDNA in 12 of 15 patients (80%).
4. 96% of patients who did not relapse had no detectable tumor DNA in their blood.
5. Patients who were found to have ctDNA had a median of 7.9 months before their relapse could be detected clinically.
6. ctDNA detection predicted relapse in all the major breast cancer subtypes (ER-positive breast cancer, ER-negative breast cancer, HER2+ breast cancer, and triple-negative breast cancer).
7. Brain metastasis in 3 patients was not detected by ctDNA.
8. ctDNA was more similar to the relapsed tumors than the original tumor.

Limitations:

While results from this study population are promising, the sample size of 55 patients is relatively small. Because the study only looked at patients who had surgery and chemotherapy, whether these findings apply to patients who have surgery only (without adjuvant chemotherapy), or to patients who have surgery followed by adjuvant chemotherapy is unknown. Additionally, the follow-up period was short—about 2 years for most patients—so whether other patients recurred after the follow-up period is also unknown. 

Conclusions:

In this study, ctDNA was found a median of 7.9 months before the patient’s recurrence was detected in a clinic, indicating that identification of circulating tumor DNA (ctDNA) may be a potentially useful blood test to predict cancer relapse. The blood test could help physicians identify patients for clinical trials to prevent relapse, because ctDNA would be identified several months before a relapse could be detected clinically. However, because of the limited sample size and specified treatments of the study population, it is unclear whether or not these results will apply to everyone with breast cancer.  But it is very promising, and more work should be done to pursue ctDNA and other liquid biopsy tests to detect cancer recurrence.

References:

Garcia-Murillas I, Schiavon G, Weigelt B, et al. “Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer.” Science Translational Medicine, Vol. 7, No. 302, Aug. 26, 2015.  

Posted 10/12/15