Wang Jianzhou, Buchholz Thomas A, Middleton Lavinia P, Allred D Craig, Tucker Susan L, Kuerer Henry M, Esteva Francisco J, Hortobagyi Gabriel N, Sahin Aysegul A
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2002 Jun 15;94(12):3107-14. doi: 10.1002/cncr.10585.
There is significant variability in the response of tumors to neoadjuvant chemotherapy, and the underlying mechanism for this variability is unknown. In this study, the authors investigated the roles of tumor nuclear grade, mitotic activity, and biomarker expression profiles in predicting the pathologic response of breast tumors to preoperative chemotherapy.
Eighty-two patients with breast carcinoma participated in two clinical trials and were treated with neoadjuvant chemotherapy, which consisted of either a conventional dose of fluorouracil, doxorubicin, and cyclophosphamide (FAC) or dose-escalated FAC. The mean age of the patients was 46 years (range, 24-69 years). Nuclear grade, mitotic activity, and biomarker profile (Her2-neu and mitosin expression patterns) in pretreatment tumors were correlated with the postchemotherapy pathologic response.
Twelve patients (15%) had a complete pathologic response (CPR), 23 patients (28%) had a near complete response (NCR), and 47 patients (57%) had significant residual disease present either at the primary site or in the axillary lymph nodes. The authors found that the nuclear grade and mitotic activity of pretreatment tumors were correlated significantly with CPR and NCR (P = 0.002 and P = 0.004). Mitosin also was correlated significantly with CPR and NCR (P = 0.028). A higher percentage of patients with Her2-neu-positive tumors had a CPR or an NCR (P = 0.152). CPR and NCR were not correlated significantly with disease stage (P = 0.186) or lymph node positivity (P = 0.498).
The current results indicate that tumor nuclear grade and tumor proliferative activity (mitotic activity and mitosin immunostaining) of pretreatment tumors in patients with breast carcinoma may serve as important indicators for the pathologic responsiveness of tumors to neoadjuvant, anthracycline-based chemotherapy.
肿瘤对新辅助化疗的反应存在显著差异，而这种差异的潜在机制尚不清楚。在本研究中，作者调查了肿瘤核分级、有丝分裂活性和生物标志物表达谱在预测乳腺肿瘤对术前化疗的病理反应中的作用。
82例乳腺癌患者参与了两项临床试验，并接受了新辅助化疗，化疗方案为常规剂量的氟尿嘧啶、多柔比星和环磷酰胺（FAC）或剂量递增的FAC。患者的平均年龄为46岁（范围24 - 69岁）。治疗前肿瘤的核分级、有丝分裂活性和生物标志物谱（Her2-neu和丝裂素表达模式）与化疗后病理反应相关。
12例患者（15%）有完全病理缓解（CPR），23例患者（28%）有近完全缓解（NCR），47例患者（57%）在原发部位或腋窝淋巴结有显著残留病灶。作者发现治疗前肿瘤的核分级和有丝分裂活性与CPR和NCR显著相关（P = 0.002和P = 0.004）。丝裂素也与CPR和NCR显著相关（P = 0.028）。Her2-neu阳性肿瘤患者中CPR或NCR的比例更高（P = 0.152）。CPR和NCR与疾病分期（P = 0.186）或淋巴结阳性情况（P = 0.498）无显著相关性。
目前的结果表明，乳腺癌患者治疗前肿瘤的核分级和肿瘤增殖活性（有丝分裂活性和丝裂素免疫染色）可能是肿瘤对基于蒽环类药物的新辅助化疗病理反应性的重要指标。
