Pinder S E, Murray S, Ellis I O, Trihia H, Elston C W, Gelber R D, Goldhirsch A, Lindtner J, Cortés-Funes H, Simoncini E, Byrne M J, Golouh R, Rudenstam C M, Castiglione-Gertsch M, Gusterson B A
Histopathology Department, the City Hospital NHS Trust, Nottingham, United Kingdom.
Cancer. 1998 Oct 15;83(8):1529-39.
Histologic grade is well recognized for its prognostic significance in cases of primary operable invasive breast carcinoma; however, the majority of studies in which grade has been assessed have been based on single-center trials. In addition, the role of grade in predicting response to chemotherapy has not been examined in many previous studies.
The authors assessed the value of Nottingham histologic grade (NHG) in a group of 465 patients enrolled in a multicenter, randomized International Breast Cancer Study Group clinical trial of adjuvant chemotherapy for patients with lymph node (LN) positive and LN negative primary breast carcinoma (formerly named Ludwig Trial V).
NHG was a predictor of overall survival for both LN negative and LN positive patients (P=0.045 and P < 0.001, respectively). NHG was associated with a poorer prognosis for both LN positive and LN negative patients, with hazard ratios of 1.651 (P < 0.001) and 1.437 (P=0.045), respectively, for an increase of one grade. Among LN negative patients, this survival disadvantage was observed only for those who received perioperative chemotherapy. For LN positive patients, an increase of one grade resulted in a significant overall survival disadvantage regardless of whether prolonged or perioperative chemotherapy was given. For LN negative patients grouped by grade, there was no observed difference in overall or disease free survival according to whether perioperative chemotherapy or no adjuvant therapy was given. However, LN positive patients with Grade 3 tumors had a significantly greater overall and disease free survival benefit from prolonged chemotherapy than from perioperative chemotherapy (P=0.016 and P=0.013, respectively); LN positive patients with Grade 1 or 2 disease in both treatment arms had comparable overall and disease free survival. A strong correlation between the previously utilized Bloom-Richardson grading system (BRG) and NHG was observed (P < 0.001 and kappa=82%) and no apparent differences in overall and disease free survival were observed between the two systems. NHG did, however, identify a greater proportion of tumors as Grade 1, and BRG identified a greater proportion of breast carcinomas as Grade 3.
This multicenter clinical study confirms the value of histologic grade, and the authors propose that this technique be used to identify Grade 3, LN positive patients who will benefit from prolonged rather than perioperative chemotherapy.
组织学分级在原发性可手术浸润性乳腺癌病例中的预后意义已得到充分认可；然而，大多数评估分级的研究都是基于单中心试验。此外，分级在预测化疗反应中的作用在以往许多研究中尚未得到检验。
作者在一组465例患者中评估了诺丁汉组织学分级（NHG）的价值，这些患者参加了一项多中心、随机的国际乳腺癌研究组针对淋巴结（LN）阳性和LN阴性原发性乳腺癌患者的辅助化疗临床试验（原名为路德维希试验V）。
NHG是LN阴性和LN阳性患者总生存的预测指标（分别为P = 0.045和P < 0.001）。NHG与LN阳性和LN阴性患者的预后较差相关，分级每增加一级，风险比分别为1.651（P < 0.001）和1.437（P = 0.045）。在LN阴性患者中，仅在接受围手术期化疗的患者中观察到这种生存劣势。对于LN阳性患者，无论给予延长化疗还是围手术期化疗，分级增加一级都会导致显著的总生存劣势。对于按分级分组的LN阴性患者，根据是否给予围手术期化疗或不给予辅助治疗，在总生存或无病生存方面未观察到差异。然而，3级肿瘤的LN阳性患者从延长化疗中获得的总生存和无病生存益处明显大于围手术期化疗（分别为P = 0.016和P = 0.013）；在两个治疗组中，1级或2级疾病的LN阳性患者的总生存和无病生存相当。观察到先前使用的布鲁姆 - 理查森分级系统（BRG）与NHG之间存在强相关性（P < 0.001，kappa = 82%），并且在两个系统之间未观察到总生存和无病生存的明显差异。然而，NHG将更多比例的肿瘤鉴定为1级，而BRG将更多比例的乳腺癌鉴定为3级。
这项多中心临床研究证实了组织学分级的价值，作者建议使用该技术来识别将从延长化疗而非围手术期化疗中获益的3级LN阳性患者。
