Schmidt M, Bremer E, Hasenclever D, Victor A, Gehrmann M, Steiner E, Schiffer I B, Gebhardt S, Lehr H-A, Mahlke M, Hermes M, Mustea A, Tanner B, Koelbl H, Pilch H, Hengstler J G
Department of Obstetrics & Gynecology, Medical School, University of Mainz, Mainz, Germany.
Br J Cancer. 2007 Jan 29;96(2):241-7. doi: 10.1038/sj.bjc.6603538. Epub 2007 Jan 9.
Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT-PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P=0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols.
紫杉醇在原发性乳腺癌的治疗中发挥着重要作用。然而，接受紫杉醇治疗的患者中有很大一部分似乎并未从该治疗中获益。我们使用从50例原发性乳腺癌中分离出的肿瘤细胞进行了一项前瞻性研究。使用ATP检测法在临床相关浓度范围（0.85 - 27.2微克/毫升紫杉醇）内测定原发性肿瘤细胞对紫杉醇的敏感性。化疗敏感性数据用于研究与免疫组织化学测定的雌激素和孕激素受体（ER和PR）状态以及组织病理学参数之间的可能关联。还通过定量RT-PCR测定孕激素受体（PR）mRNA表达。我们观察到PR状态与对紫杉醇的化疗敏感性之间存在明显关联。免疫组织化学检测到的PR表达水平较高与化疗敏感性降低相关（P = 0.008）。同样，PR mRNA表达水平高与紫杉醇化疗敏感性降低相关（P = 0.007）。与1期和2期相比，3期和4期癌的细胞敏感性较低（P = 0.013）。多元回归分析确定PR受体状态和T分期是紫杉醇化疗敏感性的独立预测因素，而ER、N分期、分级和年龄则无影响。总之，与PR阳性乳腺癌细胞相比，PR阴性乳腺癌细胞对紫杉醇的体外敏感性更高。因此，在设计新的试验和化疗方案时，应将PR状态视为一个可能的影响因素。
