Krüger Kristi, Silwal-Pandit Laxmi, Wik Elisabeth, Straume Oddbjørn, Stefansson Ingunn M, Borgen Elin, Garred Øystein, Naume Bjørn, Engebraaten Olav, Akslen Lars A
Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, Haukeland University Hospital, University of Bergen, Bergen, Norway.
Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
Sci Rep. 2021 Feb 9;11(1):3388. doi: 10.1038/s41598-021-81914-0.
A subset of breast cancer patients benefits from preoperative bevacizumab and chemotherapy, but validated predictive biomarkers are lacking. Here, we aimed to evaluate tissue-based angiogenesis markers for potential predictive value regarding response to neoadjuvant bevacizumab treatment in breast cancer. In this randomized 1:1 phase II clinical trial, 132 patients with large or locally advanced HER2-negative tumors received chemotherapy ± bevacizumab. Dual Factor VIII/Ki-67 immunohistochemical staining was performed on core needle biopsies at baseline and week 12. Microvessel density (MVD), proliferative microvessel density (pMVD; Factor VIII/Ki-67 co-expression), glomeruloid microvascular proliferation (GMP), and a gene expression angiogenesis signature score, were studied in relation to pathologic complete response (pCR), clinico-pathologic features and intrinsic molecular subtype. We found that high baseline MVD (by median) significantly predicted pCR in the bevacizumab-arm (odds ratio 4.9, P = 0.012). High pMVD, presence of GMP, and the angiogenesis signature score did not predict pCR, but were associated with basal-like (P ≤ 0.009) and triple negative phenotypes (P ≤ 0.041). pMVD and GMP did also associate with high-grade tumors (P ≤ 0.048). To conclude, high baseline MVD significantly predicted response to bevacizumab treatment. In contrast, pMVD, GMP, and the angiogenesis signature score, did not predict response, but associated with aggressive tumor features, including basal-like and triple-negative phenotypes.
一部分乳腺癌患者可从术前使用贝伐单抗和化疗中获益，但目前缺乏经过验证的预测性生物标志物。在此，我们旨在评估基于组织的血管生成标志物对于乳腺癌新辅助贝伐单抗治疗反应的潜在预测价值。在这项1:1随机II期临床试验中，132例患有大肿瘤或局部晚期HER2阴性肿瘤的患者接受了化疗±贝伐单抗治疗。在基线和第12周时对粗针活检组织进行双因子VIII/Ki-67免疫组化染色。研究了微血管密度（MVD）、增殖性微血管密度（pMVD；因子VIII/Ki-67共表达）、肾小球样微血管增殖（GMP）以及基因表达血管生成特征评分与病理完全缓解（pCR）、临床病理特征和内在分子亚型之间的关系。我们发现，高基线MVD（中位数）显著预测了贝伐单抗治疗组的pCR（优势比4.9，P = 0.012）。高pMVD、GMP的存在以及血管生成特征评分并未预测pCR，但与基底样（P≤0.009）和三阴性表型（P≤0.041）相关。pMVD和GMP也与高级别肿瘤相关（P≤0.048）。总之，高基线MVD显著预测了对贝伐单抗治疗的反应。相比之下，pMVD、GMP和血管生成特征评分并未预测反应，但与侵袭性肿瘤特征相关，包括基底样和三阴性表型。
