Rajan Radhika, Poniecka Anna, Smith Terry L, Yang Ying, Frye Deborah, Pusztai Lajos, Fiterman Derek J, Gal-Gombos Eva, Whitman Gary, Rouzier Roman, Green Marjorie, Kuerer Henry, Buzdar Aman U, Hortobagyi Gabriel N, Symmans W Fraser
Department of Pathology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Cancer. 2004 Apr 1;100(7):1365-73. doi: 10.1002/cncr.20134.
Complete pathologic response of breast carcinoma to neoadjuvant chemotherapy is a well defined outcome that correlates with prolonged survival. Categorization of incomplete response depends on accurate measurement of residual tumor size but is complicated by the variable histopathologic changes that occur within the tumor bed. In the current study, the authors investigated the contribution of assessing tumor cellularity in the pathologic evaluation of response to chemotherapy.
The slides from diagnostic core needle biopsy and the subsequent matched resection specimens were examined in 240 patients with breast carcinoma: 120 "treated" patients who received neoadjuvant chemotherapy and 120 "control" patients who received primary surgical management within a few weeks of diagnosis. Clinical response and residual tumor size were evaluated in 108 treated patients who completed a clinical trial with paclitaxel and then received combined 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Tumor cellularity was assessed from hematoxylin and eosin-stained tissue sections as the percentage of tumor area that contained invasive carcinoma.
After neoadjuvant chemotherapy, tumor cellularity decreased from a median of 40% in core needle biopsy to 10% in resection specimens (P<0.01; Wilcoxon signed rank test). The cellularity of core needle biopsy (median, 30%) tended to underestimate the cellularity of resection specimens (median, 40%) in the control group (P<0.01). Changes in cellularity varied within each clinical response category, particularly partial response and minor response. The greatest reduction was observed in the cellularity of residual primary tumors that measured < or =1 cm (pathologic T1a [pT1a] and pT1b tumors), but changes in cellularity varied in the pT1, pT2, and pT3 residual tumor categories. The shape of the distribution of tumor size, expressed as the greatest dimension in cm, was similar in the control group and the treatment group (excluding complete pathologic response); however, when residual tumor size and cellularity were combined, the distribution of pathologic response shifted left (toward complete response) with a steep decline, suggesting that many tumors had a large reduction in cellularity but little change in the tumor size.
Cellularity of the tumor mass was reduced significantly by neoadjuvant chemotherapy, and the change varied widely in different categories of clinical response. Although residual tumors measuring < or =1 cm in greatest dimension had the most reduction in tumor cellularity, there was broad variability for all residual tumor groups (pT1-pT3). The frequency distribution of residual tumor size was altered markedly by the inclusion of tumor cellularity, indicating that the product of pathologic size and tumor cellularity may provide more accurate pathologic response information than tumor size alone.
乳腺癌对新辅助化疗的完全病理缓解是一种明确的结果，与生存期延长相关。不完全缓解的分类取决于对残余肿瘤大小的准确测量，但肿瘤床内发生的组织病理学变化各异，这使其变得复杂。在本研究中，作者探讨了评估肿瘤细胞密度在化疗反应病理评估中的作用。
对240例乳腺癌患者的诊断性粗针穿刺活检切片及随后匹配的切除标本进行检查：120例“治疗”患者接受了新辅助化疗，120例“对照”患者在诊断后几周内接受了一期手术治疗。对108例完成紫杉醇临床试验并随后接受5-氟尿嘧啶、阿霉素和环磷酰胺联合化疗的治疗患者评估了临床反应和残余肿瘤大小。从苏木精和伊红染色的组织切片评估肿瘤细胞密度，即包含浸润性癌的肿瘤面积百分比。
新辅助化疗后，肿瘤细胞密度从粗针穿刺活检时的中位数40%降至切除标本中的10%（P<0.01；Wilcoxon符号秩检验）。对照组中，粗针穿刺活检的细胞密度（中位数，30%）往往低估切除标本的细胞密度（中位数，40%）（P<0.01）。每个临床反应类别中的细胞密度变化各不相同，尤其是部分缓解和微小缓解。在最大径≤1 cm的残余原发肿瘤（病理T1a[pT1a]和pT1b肿瘤）的细胞密度中观察到最大降幅，但pT1、pT2和pT3残余肿瘤类别中的细胞密度变化各不相同。以厘米为单位表示的最大径的肿瘤大小分布形状在对照组和治疗组中相似（不包括完全病理缓解）；然而，当将残余肿瘤大小和细胞密度结合起来时，病理反应的分布向左移动（趋向完全缓解），且急剧下降，这表明许多肿瘤的细胞密度大幅降低，但肿瘤大小变化不大。
新辅助化疗使肿瘤块的细胞密度显著降低，且不同临床反应类别中的变化差异很大。尽管最大径≤1 cm的残余肿瘤的肿瘤细胞密度降低最多，但所有残余肿瘤组（pT1-pT3）均存在广泛差异。残余肿瘤大小的频率分布因纳入肿瘤细胞密度而明显改变，这表明病理大小与肿瘤细胞密度的乘积可能比单独的肿瘤大小提供更准确的病理反应信息。
