Pathological Response and Circulating Tumor Cell Count Identifies Treated HER2+ Inflammatory Breast Cancer Patients with Excellent Prognosis: BEVERLY-2 Survival Data

Abstract

Purpose: The BEVERLY-2 single-arm phase II trial assessed the efficacy and safety of combining neoadjuvant chemotherapy with bevacizumab and trastuzumab for the treatment of HER2-positive inflammatory breast cancer (IBC). Here, we report the results of a preplanned survival analysis at 3 years of follow-up, along with the association between outcome and circulating biomarkers and pathologic complete response (pCR).Experimental Design: Patients received fluorouracil, epirubicin, cyclophosphamide, and bevacizumab (cycles 1-4) and docetaxel, trastuzumab, and bevacizumab (cycles 5-8) before surgery, followed by trastuzumab and bevacizumab for 30 weeks after surgery. Circulating tumor cell (CTC) and endothelial cell (CEC) counts were assessed at baseline, cycle 5, preoperative, postoperative, and at 1 year.Results: Fifty-two patients were included. The 3-year diseasefree survival (DFS) rate was 68% and overall survival (OS) rate was 90%. pCR (centrally reviewed) was strongly associated with 3-year DFS [80% and 53% in patients with/without pCR, respectively (P ¼ 0.03)]. CTC detection also independently predicted 3-year DFS [81% vs. 43% for patients with <1 vs. !1 CTC/7.5 mL at baseline (P ¼ 0.01)]. Patients with no CTCs detected at baseline and with pCR had a high 3-year DFS (95%). CEC changes during treatment had no prognostic value.Conclusions: Our study suggests that the prognosis of IBC relies on more than the achievement of pCR and highlights the role of early hematogenous tumor dissemination as assessed by CTCs. Combining these two prognostic factors isolates a subgroup of IBC with excellent survival when treated with bevacizumab-and trastuzumabcontaining regimens.

Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis

“…Finally, 50 studies were eligible for meta-analysis (Fig. 1)4591112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657.…”

Developmental therapeutics for inflammatory breast cancer: Biology and translational directions

“…In addition, clinical trial design should also take into account the positive correlation between pathologic complete response rate (pCR) with disease-free survival benefit for a subset of patients with IBC (i.e. : HER2+ IBC) as trials assessing the efficacy of neoadjuvant treatments are inherently shorter [29]. This manuscript aims to review the discoveries in the biology of IBC while highlighting the rationale for developmental therapeutics approaches.…”

Prospective study of the relevance of circulating tumor cell status and neoadjuvant chemotherapy effectiveness in early breast cancer

“…Furthermore, although we failed to find a significant association between DFS and CTC dynamic changes, all eight patients achieved both pCR and CTC‐negative conversion after NCT and were recurrence‐free within the follow‐up period. The BEVERLY‐2 trial was a prospective study that included 52 inflammatory BC patients, which is a very aggressive subtype of BC, and found that CTC‐positivity (>1 CTC/7.5 mL) dropped from 35% to 7% with NCT. Patients with at least one positive CTC had a DFS of 54%, compared with a DFS of 83% in patients where no CTCs were detected during neoadjuvant stages ( P = .018).…”