Sparano J, et al. - Researchers investigated if circulating tumor cells (CTCs) present in a peripheral blood sample attained about 5 years after diagnosis had any link with late clinical recurrence of operable human epidermal growth factor receptor 2–negative breast cancer. They found that a single positive CTC assay result 5 years following diagnosis offered independent predictive information for late clinical recurrence. This study offers proof of concept that liquid-based biomarkers could be useful for stratifying risk for late recurrence and guiding therapy.

Methods

• In this per-protocol secondary analysis of the Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab or Placebo in Patients With Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer, patients who had no clinical evidence of recurrence between 4.5 and 7.5 years after primary surgical treatment of human epidermal growth factor receptor 2–negative stage II-III breast cancer followed by adjuvant systemic therapy were enrolled from 2007 to 2011.
• After receiving consent for the subprotocol, patients were enrolled in a subprotocol for secondary analysis from February 25, 2013 to July 29, 2016.
• In April 2018, the analysis was carried out.
• For identification and enumeration of CTCs, a blood sample was attained.
• The link between a positive CTC assay result (at least 1 CTC per 7.5 mL of blood) and clinical recurrence was determined.

Results

• This analysis included a total of 547 women; 18 of 353 with hormone receptor–positive disease (5.1% [95% CI, 3.0%-7.9%]) had positive results of the CTC assay; 23 of 353 patients (6.5% [95% CI, 4.2%-9.6%]) had a clinical recurrence.
• Data revealed that the recurrence rates per person-year of follow-up in the CTC-positive and CTC-negative groups were 21.4% (7 recurrences per 32.7 person-years) and 2.0% (16 recurrences per 796.3 person-years), respectively.
• A 13.1-fold higher risk of recurrence was reported in relation to a positive CTC assay result in multivariate models including clinical covariates (hazard ratio point estimate, 13.1; 95% CI, 4.7-36.3).
• Recurrence was reported in seven of 23 patients (30.4% [95% CI, 13.2%-52.9%]); these subjects had a positive CTC assay result at a median of 2.8 years (range, 0.1-2.8 years) before clinical recurrence.
• A total of 8 of 193 patients (4.1% [95% CI, 1.8%-8.0%]) with hormone receptor–negative disease also had positive CTC assay result, although only 1 patient (0.5% [95% CI, 0%-2.9%]) experienced disease recurrence (this patient was CTC negative).