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SABCS 2019: ctDNA May Be an Independent Predictor of Disease Recurrence in Patients With Early-Stage Triple-Negative Breast Cancer


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The detection of circulating tumor DNA (ctDNA) in patients with early-stage triple-negative breast cancer treated with surgery following neoadjuvant chemotherapy is an independent predictor of disease recurrence, according to a phase II study investigating the potential of using ctDNA to detect minimal residual disease. The study findings represent an important novel stratification factor for clinical studies evaluating the ability to reduce postsurgical treatment for these patients. The study by Radovich et al was presented at the 2019 San Antonio Breast Cancer Symposium (Abstract GS5-02).

Study Methodology

The researchers analyzed plasma samples collected from patients with early-stage triple-negative breast cancer enrolled in the phase II BRE12-158 clinical trial. The study randomly assigned patients with residual disease after neoadjuvant chemotherapy to postneoadjuvant genomically-directed therapy vs physician’s choice of treatment.

The trial enrolled 196 women; ctDNA was sequenced in 142 patients using the FoundationOne Liquid Test, which profiles for 70 commonly mutated oncogenes. The presence of mutated ctDNA was associated with distant disease–free survival and overall survival in univariate analysis using the log-rank test and in multivariate analysis using the Cox proportional hazards model.

Study Findings

The researchers detected ctDNA in 90 of 142 sequenced patients (63%). TP53 was the most commonly mutated gene consistent with prior genomic studies of triple-negative breast cancer. At 17.2 months of median follow-up, detection of ctDNA was significantly associated with an inferior distant disease–free survival (median distant disease–free survival = 32.5 months vs not reached, P = .0030). At 24 months, the distant disease–free survival probability was 56% in ctDNA-positive patients compared with 81% in ctDNA-negative patients.

KEY POINTS

  • Overall, ctDNA-positive patients were three times as likely to have distant disease recurrence than ctDNA-negative patients.
  • ctDNA-positive patients had 4.1 times increased risk of death compared with ctDNA-negative patients.

In multivariate analysis, when the researchers controlled for factors—including residual cancer burden, number of positive lymph nodes, tumor size, stage, grade, age, and race—detection of ctDNA remained independently associated with inferior distant disease–free survival (hazard ratio = 3.1, 95% confidence interval = 1.4–6.8, P = .0048). Similarly, detection of ctDNA was associated with inferior overall survival, with ctDNA-positive patients experiencing an increased risk of death compared with cdTNA-negative patients.

“Detection of ctDNA in early-stage triple-negative breast cancer after neoadjuvant chemotherapy is an independent predictor of disease recurrence and represents an important novel stratification factor for future postneoadjuvant trials,” concluded the study authors.

Clinical Relevance

“If you are a woman with triple-negative breast cancer, after surgery you are in a constant ‘watch and wait’ scenario, in fear of the cancer coming back,” said lead study author Milan Radovich, PhD, Associate Professor of Surgery and Medical and Molecular Genetics at Indiana University School of Medicine, in a statement. “We know that a significant proportion of these women will have disease relapse after surgery. ctDNA is a powerful tool to be able to predict recurrence and could help us identify the best ways to manage care for women diagnosed with this disease.”

According to the study authors, a clinical trial is expected to launch in 2020 to further examine ctDNA’s potential to guide therapy for those patients at high risk for breast cancer recurrence. They also said that sequencing technology is developing rapidly and is likely to become more sensitive and more specific over time.

Disclosure: Funding for this study was provided by Vera Bradley Foundation for Breast Cancer and the Indiana University Grand Challenge Precision Health Initiative. For full disclosures of the study authors, visit abstractsonline.com.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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