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Original Investigation
August 9, 2018

Association of Circulating Tumor Cell Status With Benefit of Radiotherapy and Survival in Early-Stage Breast Cancer

Author Affiliations
  • 1Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Prentice Women’s Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 3Department of Obstetrics and Gynecology, University Hospital Ulm, Ulm, Germany
  • 4Division of Medicine-Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
JAMA Oncol. 2018;4(8):e180163. doi:10.1001/jamaoncol.2018.0163
Key Points

Question  Does circulating tumor cell status predict local recurrence or survival benefit of adjuvant radiotherapy in early-stage breast cancer?

Findings  In these cohort studies of 1697 patients from a large national database and 1516 patients from a randomized clinical trial with early-stage breast cancer who were evaluated for circulating tumor cell status, patients with at least 1 circulating tumor cell and who received radiotherapy after breast-conserving surgery had significantly longer local recurrence-free survival, disease-free survival, and overall survival compared with those who did not receive radiotherapy. Patients without circulating tumor cells did not experience longer survival outcomes after radiotherapy.

Meaning  Circulating tumor cell status may be an important predictive clinical marker for the benefit of radiotherapy in patients with early-stage breast cancer.


Importance  Circulating tumor cells (CTCs) represent the liquid component of solid tumors and are a surrogate marker for residual cancer burden. Although CTC status is prognostic of recurrence and death in breast cancer, its role in guiding clinical management remains unknown.

Objective  To determine whether CTC status is predictive of radiotherapeutic benefit in early-stage breast cancer.

Design, Setting, and Participants  The cohort studies in the present analysis included patients with stages pT1 to pT2 and pN0 to pN1 breast cancer and known CTC status from the National Cancer Database (NCDB) and the multicenter phase 3 SUCCESS clinical trial. Multivariable parametric accelerated failure time models were used to evaluate the association of CTC status and radiotherapy (RT) with survival outcomes. Data were collected from January 1, 2004, through December 31, 2014, from the NCDB cohort. The SUCCESS trial collected data from September 1, 2005, through September 30, 2013. The analyses were completed from November 1, 2016, through December 17, 2017.

Exposure  Adjuvant RT.

Main Outcomes and Measures  Overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS).

Results  A total of 1697 patients from the NCDB (16 men [0.9%] and 1681 women [99.1%]; median age, 63 years; interquartile range, 53-71 years) and 1516 patients from the SUCCESS clinical trial (median age, 52 years; interquartile range, 45-60 years) were identified. Circulating tumor cells were detected in 399 patients (23.5%) in the NCDB cohort and 294 (19.4%) in the SUCCESS cohort. The association of RT with survival was dependent on CTC status within the NCDB cohort (4-year OS, 94.9% for CTC-positive RT vs 88.0% for CTC-positive non-RT vs 93.9% for CTC-negative RT vs 93.4% for CTC-negative non-RT groups; P < .001) and 5-year DFS within the SUCCESS cohort (88.0% for CTC-positive RT vs 75.2% for CTC-positive non-RT vs 92.3% for CTC-negative RT vs 88.3% for CTC-negative non-RT; P = .04). In the NCDB cohort, RT was associated with longer OS in patients with CTCs (time ratio [TR], 2.04; 95% CI, 1.55-2.67; P < .001), but not in patients without CTCs (TR, 0.80; 95% CI, 0.52-1.25; P = .33). In the SUCCESS cohort, CTC-positive patients treated with RT exhibited longer LRFS (TR, 2.73; 95% CI, 1.62-4.80; P < .001), DFS (TR, 3.03; 95% CI, 2.22-4.13; P < .001), and OS (TR, 1.83; 95% CI, 1.23-2.72; P = .003). Among patients from both cohorts who underwent breast-conserving surgery, RT was associated with longer OS in patients with CTCs (TR, 4.37; 95% CI, 2.71-7.05; P < .001) but not in patients without CTCs (TR, 0.87; 95% CI, 0.47-1.62; P = .77). Radiotherapy was not associated with OS after mastectomy in CTC-positive or CTC-negative patients.

Conclusions and Relevance  Treatment with RT was associated with longer LRFS, DFS, and OS in patients with early-stage breast cancer and detectable CTCs. These results are hypothesis generating; a prospective trial evaluating CTC-based management for RT after breast-conserving surgery in women with early-stage breast cancer is warranted.