Molecular Alterations in Lobular/Ductal Breast Cancer

小叶型乳腺癌在形态和临床上都不同于更常见的导管型。它们在类固醇激素受体表达和增殖率方面也不同。表现出小叶形态的乳腺癌细胞也可能在等位基因丢失模式和确定途径的组分方面不同，例如e-钙粘蛋白/连环蛋白和BRCA 1/BRCA 2介导的DNA修复。评估小叶癌的独特特征一直很困难，大多数研究只能评估少数这种相对罕见的肿瘤类型。将收集超过350份浸润性小叶和导管乳腺癌的组织样本，并检测乳腺癌相关蛋白的表达，作为NCI资助的病例对照研究的一部分，以评估55-79岁女性中使用联合激素替代疗法（CHRT）与浸润性小叶和导管乳腺癌发病率之间的相关性。使用研究中收集的组织样品，我们建议1）评估350例浸润性小叶癌和导管癌中p53等位基因丢失、突变和蛋白质过表达率的差异，和2）使用新开发的微阵列技术（HuSNP）评估100例小叶癌和导管癌中等位基因丢失率的全基因组差异。作为母研究的一部分，正在仔细收集的大量数据也将使我们能够探索BRCA相关DNA修复组分和e-钙粘蛋白异常的改变对其他肿瘤表型（如ER和PR阳性或阴性亚组）的贡献。对大量小叶癌和导管癌的全基因组洛缺失扫描将提供迄今为止小叶癌等位基因缺失的最全面的描述。从研究大量小叶癌中获得的形态学特异性特征的信息可能会增加对乳腺癌不同子集生物学的理解，为将患者分层为预后和治疗组的研究提供基础，并/或为特定肿瘤类型的靶向治疗提供信息。

Lobular breast cancers differ both morphologically and clinically from the more common ductal type. They also differ in steroid hormone receptor expression and proliferation rates. Breast cancer cells demonstrating a lobular morphology may also be distinct with respect to allelic loss patterns and components of defined pathway, such as e- cadherin/catenin and BRCA1/BRCA2-mediated DNA repair. It has been difficult to assess the unique characteristics of lobular cancer most studies can only evaluate a small number of this relative uncommon tumor type. Over 350 tissue samples each of invasive lobular and ductal breast cancer will be collected and tested for expression of breast cancer- related proteins as part of an NCI-funded case-control study to assess associations between the use of combined hormone replacement therapy (CHRT) and the incidence of both invasive lobular and ductal breast cancer in women aged 55-79. Using the tissue samples collected in the study, we propose to 1) evaluate the difference in the rates of p53 allelic loss, mutation and protein over-expression in 350 each of invasive lobular and ductal cancers and 2) evaluate the difference in the genome- wide rate of allelic loss in 100 each of lobular and ductal cancers using newly developed microarray techniques (HuSNP). The large amount of data that is being carefully collected as part of the parent study will also allow us explore the contribution of alterations in BRCA-related DNA repair components and e-cadherin abnormalities to other tumor phenotypes such as ER and PR positive or negative subgroups. The genome-wide scan for LOH in a large set of lobular and ductal cancers will provide the most comprehensive description of allelic loss on lobular cancer to date. Information about morphology-specific traits gained from studying a large number of lobular cancers could lead to an increased understanding of the biology of distinct subsets of breast cancer, provide a basis for studies that would define patient stratification into prognostic and treatment groups and/or inform the development of targeted therapies for specific tumor types.