Foekens J A, Rio M C, Seguin P, van Putten W L, Fauque J, Nap M, Klijn J G, Chambon P
Division of Endocrine Oncology, Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Cancer Res. 1990 Jul 1;50(13):3832-7.
Application of systemic adjuvant therapy for primary breast cancer patients requires a more accurate identification of patients at high risk for recurrence. We have quantitatively assessed the cytosolic levels of estrogen-regulated pS2 protein in tumors of 205 breast cancer patients (median follow-up, 47 mo). There were no significant associations between the level of pS2 protein and tumor size, lymph node status, and differentiation grade. Using length of relapse-free survival (RFS) and overall survival (OS) as end points, 11 ng of pS2 protein/mg of cytosol protein were found as the best cutoff level to discriminate between positive (pS2+) and negative (pS2-). Patients with pS2- tumors showed significantly shorter RFS and OS (P less than 0.0001) than patients with pS2+ tumors. Also after adjustment for tumor size, lymph node status, and estrogen receptor (ER) status, pS2 negativity was associated with earlier recurrence and death. Tumors positive for pS2 (55 of 205, 27%) were almost exclusively confined to the subclass of ER+ tumors (53 of 55, 96%). The death rate for patients with pS2+ tumors was one-tenth of the death rate for patients with pS2-/ER- tumors. In the patients with ER+ tumors, the prognostic power of the pS2 status was especially present in patients whose tumors were also positive for the progesterone receptor (5-yr RFS and OS, 85% and 97% for ER+/PgR+/pS2+ tumors compared with 50% and 54% for the patients with ER+/PgR+/pS2- tumors). In patients with axillary lymph node involvement (N+), pS2 status could discriminate strongly between a good and bad prognosis group (5-yr RFS and OS, 65% and 88% for N+/pS2+ compared with 32% and 34% for N+/pS2-). A similar phenomenon was observed in patients without axillary lymph node involvement (5-yr RFS and OS, 89% and 95% for N0/pS2+ compared with 58% and 82% for N0/pS2-). We conclude that the pS2 status of human primary breast tumors is an important variable for the identification of patients at high risk for recurrence and death. Knowledge of the cytosolic pS2 status appeared of particular importance to identify patients at high risk in the ER+/PgR+ subclass of tumors, and in both the N0 and N+ subclasses of patients.
对原发性乳腺癌患者应用全身辅助治疗需要更准确地识别复发高危患者。我们定量评估了205例乳腺癌患者肿瘤中雌激素调节的pS2蛋白的胞质水平（中位随访时间为47个月）。pS2蛋白水平与肿瘤大小、淋巴结状态及分化程度之间无显著相关性。以无复发生存期（RFS）和总生存期（OS）为终点，发现11 ng pS2蛋白/毫克胞质蛋白是区分阳性（pS2+）和阴性（pS2-）的最佳临界值。pS2-肿瘤患者的RFS和OS显著短于pS2+肿瘤患者（P<0.0001）。在对肿瘤大小、淋巴结状态和雌激素受体（ER）状态进行校正后，pS2阴性仍与早期复发和死亡相关。pS2阳性的肿瘤（205例中的55例，27%）几乎仅局限于ER+肿瘤亚类（55例中的53例，96%）。pS2+肿瘤患者的死亡率是pS2-/ER-肿瘤患者死亡率的十分之一。在ER+肿瘤患者中，pS2状态的预后价值在孕激素受体也为阳性的患者中尤为明显（ER+/PgR+/pS2+肿瘤患者的5年RFS和OS分别为85%和97%，而ER+/PgR+/pS2-肿瘤患者分别为50%和54%）。在有腋窝淋巴结转移（N+）的患者中，pS2状态能有力地区分预后良好和不良的组（N+/pS2+患者的5年RFS和OS分别为65%和88%，而N+/pS2-患者分别为32%和34%）。在无腋窝淋巴结转移的患者中也观察到类似现象（N0/pS2+患者的5年RFS和OS分别为89%和95%，而N0/pS2-患者分别为58%和82%）。我们得出结论，人类原发性乳腺肿瘤的pS2状态是识别复发和死亡高危患者的一个重要变量。了解胞质pS2状态对于识别肿瘤ER+/PgR+亚类以及N0和N+亚类患者中的高危患者尤为重要。
