SAN ANTONIO (FRONTLINE MEDICAL NEWS) – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.