Institute of Pathology, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
Arch Gynecol Obstet. 2013 Feb;287(2):337-44. doi: 10.1007/s00404-012-2534-9. Epub 2012 Sep 6.
Identifying biomarkers that can predict the prognosis and treatment response is helpful for individualizing breast cancer (BC) therapy. A neoadjuvant treatment setting is ideal for testing biomarkers capable of predicting the treatment response. This study analyzed the value of immunohistochemical biomarkers for predicting pathological complete response (pCR) and prognosis in a group of BC patients receiving standardized treatment.
A total of 100 BC patients were treated with neoadjuvant chemotherapy (four cycles of epirubicin and cyclophosphamide) between 2000 and 2005. Formalin-fixed and paraffin-embedded core biopsies were taken before chemotherapy for immunohistochemical staining of ER, PgR, HER2, Bcl-2, p53, cyclin D1, CK5/6, CK8, CK18, and TOP2A. Patient and tumor characteristics and biomarker scores were used to predict pCR and prognosis, using logistic regression and Cox proportional hazard models.
pCR was achieved in 11 patients and was predicted by the established marker Ki-67. In addition, CK5/6 and CK18 improved the prediction model and were associated with lower pCR rates. For the prognosis, only the established markers nodal status, Ki-67, and PgR predicted overall survival and nodal status; Ki-67 and PgR predicted distant disease-free survival.
In this small retrospective study, CK5/6 and CK18 appeared to improve prediction of pCR in addition to the established markers. CK5/6 may indicate a tumor type resembling a basal phenotype that is more resistant to anthracycline-based therapy, and CK18 may indicate a luminal subtype that is more resistant to chemotherapy. However, these results need to be replicated in larger studies.
识别能够预测预后和治疗反应的生物标志物有助于乳腺癌（BC）个体化治疗。新辅助治疗环境是测试能够预测治疗反应的生物标志物的理想环境。本研究分析了一组接受标准化治疗的 BC 患者中免疫组织化学生物标志物预测病理完全缓解（pCR）和预后的价值。
2000 年至 2005 年间，共有 100 例 BC 患者接受新辅助化疗（环磷酰胺和表柔比星 4 个周期）。在化疗前进行福尔马林固定和石蜡包埋核心活检，进行 ER、PgR、HER2、Bcl-2、p53、cyclin D1、CK5/6、CK8、CK18 和 TOP2A 的免疫组化染色。使用逻辑回归和 Cox 比例风险模型，根据患者和肿瘤特征以及生物标志物评分预测 pCR 和预后。
11 例患者达到 pCR，由既定标志物 Ki-67 预测。此外，CK5/6 和 CK18 改善了预测模型，与较低的 pCR 率相关。对于预后，只有既定标志物淋巴结状态、Ki-67 和 PgR 预测总生存期和淋巴结状态；Ki-67 和 PgR 预测远处无病生存期。
在这项小型回顾性研究中，CK5/6 和 CK18 似乎除了既定标志物外，还改善了 pCR 的预测。CK5/6 可能表明肿瘤类型类似于基底表型，对蒽环类药物为基础的治疗更具耐药性，而 CK18 可能表明对化疗更具耐药性的管腔亚型。然而，这些结果需要在更大的研究中复制。
