Clin Cancer Res：RB基因缺乏的乳腺癌患者更适合接受新辅助化疗

根据一项于2012年7月18日在线发表在Clinical Cancer Research期刊上的回顾性研究，来自美国托马斯杰斐逊大学医院和基梅尔癌症中心的研究人员报道，缺乏一种被称作视网膜母细胞瘤基因(retinoblastoma, RB)的肿瘤抑制基因的乳腺癌患者对新辅助化疗(neoadjuvant chemotherapy)作出更好的反应。

在这项研究中，研究人员对1000多名接受过新辅助疗法(neoadjuvant therapy)的乳腺癌患者开展基因表达谱分析来鉴定那些缺乏基因RB的病人，同时还进行直接组织学分析。这些病人代表着不同的乳腺癌亚型，并接受不同用药方案的治疗。

研究人员发现基因RB缺失与大多数乳腺癌亚型对所有已研究的新辅助疗法的反应发生改善相关联。

总之，这些数据表明基因RB缺失可能是一种有用的生物分子标记物来确定对新辅助化疗作出更好反应的乳腺癌患者。基因这些发现，研究人员已启动一项前瞻性的临床试验以便评估RB和另一种分子标记物PTEN与乳腺癌对新辅助化疗作出的反应之间存在的关联性。

本文编译自Breast cancer patients who lack RB gene respond better to neoadjuvant chemotherapy

doi: 10.1158/1078-0432.CCR-12-0903
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RB-pathway Disruption is Associated with Improved Response to Neoadjuvant Chemotherapy in Breast Cancer

Agnieszka K. Witkiewicz1,*, Adam Ertel2, Jeanne M. McFalls3, Matias E Valsecchi4, Gordon Schwartz5, and Erik S. Knudsen

Purpose: We sought to determine whether dysregulation of the RB tumor suppressor pathway was associated with improved response to neoadjuvant chemotherapy in breast cancer. Experimental Design: An RB-loss signature was used to analyze the association between pathway status and pathological complete response in gene expression datasets encompassing three different neoadjuvant regimens. Parallel immunohistochemical analysis of the RB-pathway was performed on pretreatment biopsies to determine the association with pathological response to neoadjuvant chemotherapy. Results: An RB loss gene expression signature was asssociated with increased pathological complete response in datasets from breast cancer patients treated neoadjuvant therapy encompasssing approximately 1,000 patients. The association with improved response to neoadjuvant chemotherapy was true in both ER-positive and ER-negative breast cancer. Elevated expression of p16ink4a is associated with the RB-loss of signature (R=0.493-0.5982), and p16ink4a mRNA levels were strongly associated with pathological complete response. In an independent cohort, immunohistochemical analyses of RB and p16ink4a revealed an association of RB loss (p=0.0018) or elevated p16ink4a (p=0.0253) with pathological complete response. Additionally, by Miller-Payne and Clinical-Pathologic Scoring (CPS) analyses, RB-deficient tumors experienced an overall improved response to neoadjuvant chemotherapy. Conclusion: Disruption of the RB-pathway as measured by several independent methods was associated with improved response to neoadjuvant chemotherapy. The RB-pathway status was relevant for pathological response in both ER-positive and ER-negative breast cancer with similar results observed with multiple chemotherapy regimens. Combined, these data indicate that RB-status is associated with the response to neoadjuvant chemotherapy in breast cancer and could be employed to inform treatment.