We developed a functional ex vivo anthracycline-based sensitivity test. Surgical resection material of primary breast cancer (BC) was used to determine criteria for the ex vivo sensitivity assay based on morphology, proliferation and apoptosis. Subsequently, a proof-of-concept study was performed correlating results of this assay on primary BC biopsies with in vivo response after treatment with anthracycline-containing neoadjuvant chemotherapy (NAC). Cut off values for the ex vivo anthracycline-based sensitivity test were established based on analysis of 21 primary breast tumor samples obtained after surgery. In the proof-of-concept study based on a new set of tumor biopsies, 41 patients were included. Eight biopsies did not contain tumor cells and three patients could not be biopsied for various reasons. In the remaining 30 biopsies, the success rate of the ex vivo test was 77% (23/30); six out of seven failed tests were due to excessive apoptosis, our pre-specified test criteria. Of the 23 patients with a successful ex vivo test result, three patients did not undergo NAC after the biopsy. Here we report the ex vivo anthracycline-based sensitivity assay is feasible on biopsy material and shows 75% concordance between ex vivo outcomes and in vivo MRI response. Unfortunately, the percentage of unsuccessful tests is rather high. This study provides the foundation for further development of ex vivo sensitivity assays.

我们开发了一种基于蒽环类药物的功能性离体敏感性测试。原发性乳腺癌 (BC) 的手术切除材料用于根据形态、增殖和凋亡确定离体敏感性测定的标准。随后，进行了一项概念验证研究，将原发性 BC 活检的检测结果与含蒽环类新辅助化疗 (NAC) 治疗后的体内反应相关联。基于对手术后获得的 21 个原发性乳腺肿瘤样本的分析，建立了基于蒽环类药物的离体敏感性测试的截止值。在基于一组新的肿瘤活检的概念验证研究中，纳入了 41 名患者。8 例活检未发现肿瘤细胞，3 名患者因各种原因无法进行活检。其余30个活检中，离体测试的成功率为77%（23/30）；七分之六的失败测试是由于过度细胞凋亡，这是我们预先指定的测试标准。在 23 名离体测试结果成功的患者中，有 3 名患者在活检后没有接受 NAC。在这里，我们报告基于体外蒽环类药物的敏感性测定在活检材料上是可行的，并且显示体外结果和体内 MRI 反应之间有 75% 的一致性。不幸的是，不成功测试的百分比相当高。该研究为进一步开发离体敏感性测定奠定了基础。