Research and Development, Agendia BV, Amsterdam, The Netherlands.
Breast Cancer Res Treat. 2012 May;133(1):37-47. doi: 10.1007/s10549-011-1683-z. Epub 2011 Aug 4.
Classification of breast cancer into molecular subtypes maybe important for the proper selection of therapy, as tumors with seemingly similar histopathological features can have strikingly different clinical outcomes. Herein, we report the development of a molecular subtyping profile (BluePrint), that enables rationalization in patient selection for either chemotherapy or endocrine therapy prescription. An 80-Gene Molecular Subtyping Profile (BluePrint) was developed using 200 breast cancer patient specimens and confirmed on four independent validation cohorts (n = 784). Additionally, the profile was tested as a predictor of chemotherapy response in 133 breast cancer patients, treated with T/FAC neoadjuvant chemotherapy. BluePrint classification of a patient cohort that was treated with neoadjuvant chemotherapy (n = 133) shows improved distribution of pathological Complete Response (pCR), among molecular subgroups compared with local pathology: 56% of the patients had a pCR in the Basal-type subgroup, 3% in the MammaPrint Low-risk, Luminal-type subgroup, 11% in the MammaPrint High-risk, Luminal-type subgroup, and 50% in the HER2-type subgroup. The group of genes identifying Luminal-type breast cancer is highly enriched for genes having an Estrogen Receptor binding site proximal to the promoter-region, suggesting that these genes are direct targets of the Estrogen Receptor. Implementation of this profile may improve the clinical management of breast cancer patients, by enabling the selection of patients who are most likely to benefit from either chemotherapy or from endocrine therapy.
乳腺癌的分子亚型分类对于选择合适的治疗方法可能很重要，因为具有相似组织病理学特征的肿瘤可能具有截然不同的临床结局。在此，我们报告了一种分子亚型分类方案（Blueprint）的开发，该方案可实现患者选择化疗或内分泌治疗方案的合理化。使用 200 例乳腺癌患者标本开发了 80 基因分子亚型分类方案（Blueprint），并在四个独立的验证队列（n=784）中得到了验证。此外，该方案还在 133 例接受 T/FAC 新辅助化疗的乳腺癌患者中作为化疗反应的预测因子进行了测试。在接受新辅助化疗的患者队列（n=133）中，BluePrint 分类显示与局部病理学相比，病理完全缓解（pCR）在分子亚组中的分布得到了改善：基底型亚组中有 56%的患者达到 pCR，MammaPrint 低危型、Luminal 型亚组中有 3%，MammaPrint 高危型、Luminal 型亚组中有 11%，HER2 型亚组中有 50%。确定 Luminal 型乳腺癌的基因组高度富含具有接近启动子区域的雌激素受体结合位点的基因，这表明这些基因是雌激素受体的直接靶标。该方案的实施可能通过选择最有可能从化疗或内分泌治疗中获益的患者来改善乳腺癌患者的临床管理。
