Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Breast Cancer Res Treat. 2012 Nov;136(1):35-43. doi: 10.1007/s10549-012-2233-z. Epub 2012 Sep 8.
Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.
浸润性小叶癌（ILC）的新辅助化疗（NAC）反应率低于浸润性导管癌（IDC）已有报道。我们旨在通过分析肿瘤特征，如蛋白表达、基因表达和影像学特征，并在调整这些因素后，比较 IDC 的 NAC 反应率，来确定 ILC 组织学是否确实预示着对 NAC 的不良反应。我们合并了两项大型前瞻性 NAC 试验的数据，共纳入 676 例患者，其中 75 例为小叶癌。合格患者的肿瘤直径≥3cm 或有病理证实的阳性淋巴结，并接受了连续活检、表达微阵列分析和 MRI 成像。我们比较了 ILC 和 IDC 的病理完全缓解（pCR）率和保乳手术（BCS）率，并对临床病理因素进行了调整。单因素分析显示，NAC 后 ILC 的 pCR 率明显低于 IDC（11%比 25%，p=0.01）。然而，两种组织学类型之间的肿瘤特征差异，包括激素受体（HR）状态、HER2 状态、组织学分级和 p53 表达，解释了这种差异，两种类型中 HR+/HER2-肿瘤的 pCR 率最低（分别为 7%和 5%）。HR-和/或 HER2+的 ILC 的 pCR 率为 25%。表达亚型，特别是 NKI 70 基因标志物，与 pCR 相关，尽管每组 ILC 的数量较少，无法得出显著关联。在调整分子特征后，IDC 和 ILC 的 BCS 率无差异。我们得出结论，ILC 代表一组异质性肿瘤，对 NAC 的反应性低于 IDC。然而，这种差异是由分子特征的差异解释的，特别是 HR 和 HER2，而与小叶癌组织学无关。
