Abstract
PurposeAddition of bevacizumab to trastuzumab-based neoadjuvant chemotherapy in HER2-positive inflammatory breast cancer (IBC) was associated with favorable outcome in the BEVERLY-2 phase II trial. Circulating levels of matrix metalloproteinases (MMP) 2 and 9 were correlated to high response rate and prolonged survival in high-grade glioma treated with bevacizumab. We examined the prognostic impact of MMP2 and MMP9 serum levels in BEVERLY-2 patients.Experimental designMMP2 and MMP9 serum levels were assessed using ELISA at baseline and before surgery in 45/52 available samples. Correlations were tested with pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS).ResultsBaseline (b) MMP2 and MMP9 serum levels were independent from patient characteristics and circulating tumor or endothelial cells, and were not correlated to pCR. High bMMP2 was correlated to better DFS (p=0.001) and OS (p=0.032), while low bMMP9 was correlated to better OS (p=0.022) and tended to be associated with longer DFS (p=0.071). In multivariate analyses, bMMP2 (p=0.003, Hazard Ratio [HR]: 0.115) and bMMP9 (p=0.041, HR: 3.511) remained correlated to DFS. As continuous variables, bMMP2 was associated with relapse (p=0.002) and death (p=0.049), while bMMP9 was associated with death (p=0.035). During treatment, significant increase in MMP2 and decrease in MMP9 levels (p<0.001 for both) were observed in 100% and 87% of patients respectively.ConclusionsHigh bMMP2 and low bMMP9 serum levels were associated with better survival in HER2-positive IBC patients treated with bevacizumab- and trastuzumab-based neoadjuvant chemotherapy. Their predictive value of bevacizumab benefit should be evaluated in a randomized trial.
Highlights
Inflammatory breast cancer (IBC) is an uncommon (5% of all cases) but highly aggressive form of breast cancer [1]
BMMP2 was associated with relapse (p=0.002) and death (p=0.049), while bMMP9 was associated with death (p=0.035)
High bMMP2 and low bMMP9 serum levels were associated with better survival in HER2-positive inflammatory breast cancer (IBC) patients treated with bevacizumab- and trastuzumab-based neoadjuvant chemotherapy
Summary
Inflammatory breast cancer (IBC) is an uncommon (5% of all cases) but highly aggressive form of breast cancer [1]. Even though significant improvements were achieved with multimodal treatment, the 5-year survival rate is only ~ 40%, and the prognosis of IBC remains worse than that of non-inflammatory locally advanced breast cancer [1]. IBC remains poorly understood but includes a high vascularity and an increased micro-vessel density consistent with a high expression of angiogenic factors, including the vascular endothelial growth factor (VEGFA) [2]. This led to the evaluation of anti-angiogenic therapies in this disease. Biomarkers able to predict bevacizumab benefit in breast cancer, including HER2-positive IBC, would be of a crucial interest.
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