Circulating tumor cells may predict radiotherapy benefit in early-stage breast cancer

Radiotherapy appeared associated with longer RFS, DFS and OS among patients with early-stage breast cancer who had detectable circulating tumor cells, according to study results.

“The detection of even a single circulating tumor cell has been shown to be prognostic of shorter RFS and OS,” Chelain R. Goodman, MD, PhD, resident in the radiation oncology department at Northwestern University Feinberg School of Medicine, and colleagues wrote. “Circulating tumor cell status has also been shown to be prognostic of failure of locoregional and adjuvant systemic treatments. ... No data are yet available regarding circulating tumor cell status as a predictive factor of the benefit of radiotherapy in early-stage breast cancer.”

The researchers analyzed data from 1,697 patients (16 men and 1,681 women; median age, 63 years) with early-stage breast cancer included in the National Cancer Database (NCDB), as well as 1,516 patients (median age, 52 years) from the SUCCESS trial, a prospective, multicenter phase 3 trial of women who had nonmetastatic breast cancer and one or more high-risk factors. In the SUCCESS trial, researchers randomly assigned women to one of two chemotherapy regimens.

Goodman and colleagues used multivariable parametric accelerated failure time models to evaluate whether circulating tumor cells and radiotherapy receipt were associated with survival.

Nearly one-quarter (23.5%) of patients from the NCDB sample and one-fifth (19.4%) of the SUCCESS cohort had detectable circulating tumor cells.

In the NCDB cohort, results showed circulating tumor status predicted survival benefit from radiotherapy. Among those with detectable circulating tumor cells, 4-year OS rates were 94.9% for those who received radiotherapy and 88% for those who did not. Among those without detectable circulating tumor cells, 4-year OS rates were 93.9% for those who received radiotherapy and 93.4% for those who did not (P < .001 for all).

Radiotherapy appeared associated with longer OS among patients with detectable circulating tumor cells (time ratio, 2.04; 95% CI, 1.55-2.67) but not among patients without circulating tumor cells (time ratio, 0.8; 95% CI, 0.52-1.25).

Researchers observed similar results in the SUCCESS trial cohort.

Among those with detectable circulating tumor cells, 5-year DFS rates were 88% for those who received radiotherapy and 75.2% for those who did not. Among those without detectable circulating tumor cells, 5-year DFS rates were 92.3% for those who received radiotherapy and 88.3% for those who did not (P = .04 for all).

Among patients with detectable circulating tumor cells, those who received radiotherapy achieved longer local RFS (time ratio, 2.73; 95% CI, 1.62-4.8), DFS (time ratio, 3.03; 95% CI, 2.22-4.13) and OS (time ratio, 1.83; 95% CI, 1.23-2.72).

Researchers also assessed the benefit of radiotherapy for patients from both the NCDB and SUCCESS trial cohorts who underwent breast-conserving surgery. Results showed radiotherapy appeared associated with longer OS among those with circulating tumor cells (time ratio, 4.37; 95% CI, 2.71-7.05), but not those without circulating tumor cells (time ratio, 0.87; 95% CI, 0.47-1.62).

Radiotherapy did not appear linked to OS among patients who underwent mastectomy, regardless of their circulating tumor cell status.

“A clinical need exists for more effective biomarkers to predict the benefit of adjuvant radiation therapy for women with early-stage breast cancer,” Corey Speers, MD, PhD, assistant professor at University of Michigan Comprehensive Cancer Center, and Hope S. Rugo, MD, clinical professor at UCSF Helen Diller Family Comprehensive Cancer Center, wrote in an accompanying editorial. “Just as the development of molecularly based signatures provided some degree of clarity about the value of adjuvant chemotherapy [for] women with early-stage, ER-positive breast cancer, the development of prognostic and predictive signatures to determine the need for and efficacy of adjuvant radiation therapy holds similar promise.”

However, efforts to quantify circulating tumor cells remain challenging, and the process is not feasible for all patients, Speers and Rugo wrote.

“Whether circulating tumor cells, circulating tumor DNA, or other signatures will gain traction remains to be seen,” Speers and Rugo wrote. “Ultimately, for these tests to be translated to the clinic, we need further evidence of accuracy, reproducibility and efficacy in prospectively designed trials.” – by Andy Polhamus

Disclosures: The authors report no relevant financial disclosures. Speers and Rugo report no relevant financial disclosures.