Circulating Tumor Cell Clearance Kinetics in Patients Undergoing Adjuvant Radiotherapy for Node-Positive Breast Cancer: A Prospective Observational Cohort Study

• Published in: International journal of radiation oncology, biology, physics Vol. 120; no. 2; pp. S199 - S200
• Main Authors: Goodman, C.R., Strauss, J.B., Shaitelman, S.F., Smith, B.D., Zia, A., Comeaux, N.I., Nead, K.T., Mitchell, M.P., Hoffman, K.E., Strom, E.A., Stauder, M.C., Perkins, G.H., Reed, V.K., Bloom, E., Joyner, M.M., Schlembach, P.J., Barcenas, C.H., Lucci, A., Woodward, W.A.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-10-2024
• ISSN: 0360-3016
• DOI: 10.1016/j.ijrobp.2024.07.2261

This is a prospective observational cohort study to evaluate dynamics of circulating tumor cells (CTCs) with adjuvant breast radiotherapy (RT). We present a per-protocol planned interim analysis triggered at 12 months following study activation.
Eligible patients with clinical or pathologic T3-4 or node-positive non-metastatic Her2-negative breast cancer dispositioned to receive RT were prospectively enrolled. All patients received RT to the breast/chest wall and regional (axillary, infraclavicular, supraclavicular, and internal mammary) lymph nodes with a boost to unresected involved nodes. CTCs were enumerated using the CellSearch® assay at up to 3 timepoints: immediately prior to RT (Pre-RT), within 1 week of completing RT (End of RT), and at follow-up 3-6 months after RT (Post-RT). Rates of CTC detection and clearance with RT were calculated. Associations between clinicopathologic variables and Pre-RT CTC status were determined using the Chi-square or Fisher exact test.
As of March 2024, 100 patients had a Pre-RT assessment. Seventy-three (73%) of patients had estrogen receptor-positive disease, 61 (61%) received neoadjuvant chemotherapy (NAC), 68 (68%) underwent mastectomy, and 63 (63%) had axillary lymph node dissection. Prior to RT, 22 (22%) patients had ≥1 detectable CTC (median=1 cell [1-2]), of which 16 (72%) had received NAC. Of the 19 CTC-positive patients with completed subsequent blood draws, 17 (89%) and 19 (100%) were CTC-negative at the “End of RT” and “Post-RT” timepoints, respectively. CTC-positive status was significantly associated with more advanced clinical tumor stage (p=0.05) and nodal stage (p=0.05) but not with pathologic complete response (pCR). Patients with detectable CTCs Pre-RT were significantly more likely to have disease in the supraclavicular or infraclavicular nodal basins or internal mammary chain (cN3) (36% vs 12%, p=0.02) or a diagnosis of inflammatory breast cancer (IBC) (22% vs 4%, p=0.02). Of the 4 CTC-positive patients with pCR, 3 had cN3 disease and 1 had IBC.
IBC and cN3 disease were significantly associated with detection of CTCs immediately prior to RT, including patients with pCR. Following comprehensive RT, 100% of CTC-positive patients experienced CTC clearance. While delayed clearance of CTCs without RT cannot be assessed on this single arm study, particularly in the setting of additional systemic therapy (endocrine therapy; CDK4/6 inhibitors), these results support the hypothesis that CTC status may represent a real-time biomarker for residual locoregional disease prior to RT, even among patients with pCR, as well as a potential surrogate for radiotherapeutic efficacy. Future studies will assess banked circulating tumor DNA and association of circulating tumor material with clinical outcomes.