Circulating Tumor Cells Predict Response in Inflammatory Breast Cancer

The presence of circulating tumor cells (CTCs) at baseline was associated with decreased overall and disease-free survival in patients with inflammatory breast cancer undergoing treatment with neoadjuvant chemotherapy combined with bevacizumab, according to a pooled analysis of two trials.

“Inflammatory breast cancer is a highly aggressive form of locally advanced breast cancer representing up to 5% of breast cancers,” wrote study authors led by Jean-Yves Pierga, MD, PhD, of Institut Curie in Paris. CTC count has been shown to have prognostic value in early breast cancer; the value of circulating endothelial cells (CECs) remains controversial.

The new analysis included 152 patients with inflammatory breast cancer treated with bevacizumab and neoadjuvant chemotherapy; those in the BEVERLY-1 trial had HER2-negative tumors and were treated with docetaxel, and those in the BEVERLY-2 trial had HER2-positive breast cancer and were treated with docetaxel plus trastuzumab. CECs and CTCs were measured at baseline; the results were published online ahead of print in Annals of Oncology.

At baseline, 55 patients (39% of 141 evaluable) had detectable CTCs; there was no correlation between CTC detection and any patient characteristics, or between CTC and CEC counts. After 4 cycles of chemotherapy the rate of CTC detection dropped to 9% (P < .001). This remained low before surgery (9%) and after surgery (6%). The median CEC count at baseline increased during docetaxel/bevacizumab therapy (P < .001), then progressively decreased following surgery.

Forty percent of patients achieved a pathologic complete response (pCR) after therapy; there was no correlation between pCR and baseline CTC (P = .31) or between pCR and CTC decrease (P = .37).

There was, however, a significant correlation between CTC detection at baseline and survival outcomes. The 3-year disease-free survival rate was 70% in those with no CTC detection at baseline, compared with 39% for those with CTC detection, for a hazard ratio of 2.80 (95% CI, 1.65–4.76; P < .01). The 3-year overall survival rates were 92% and 56% (P < .01), respectively. No such correlation was seen with CECs. On a multivariate analysis, only triple-negative status, lack of pCR, and baseline CTC status were significant predictors for shorter disease-free and overall survival.

Combining pCR and baseline CTC status could thus offer a subset of patients with excellent prognosis, the authors wrote. Patients in that category had a 3-year disease-free survival rate of 88% and a 3-year overall survival rate of 94%; those with baseline CTCs and no pCR had a 3-year disease-free survival rate of 34% and a 3-year overall survival rate of 48%.

“This observation suggests that the therapeutic response cannot totally revert the poor prognosis associated to the presence of CTC,” the authors wrote. “We suggest that CTC count at baseline could be part of inflammatory breast cancer stratification in future prospective trials.”