根據(jù)一項于2012年7月18日在線發(fā)表在Clinical Cancer Research期刊上的回顧性研究,，來自美國托馬斯杰斐遜大學(xué)醫(yī)院和基梅爾癌癥中心的研究人員報道,，缺乏一種被稱作視網(wǎng)膜母細(xì)胞瘤基因(retinoblastoma, RB)的腫瘤抑制基因的乳腺癌患者對新輔助化療(neoadjuvant chemotherapy)作出更好的反應(yīng)。
在這項研究中,，研究人員對1000多名接受過新輔助療法(neoadjuvant therapy)的乳腺癌患者開展基因表達譜分析來鑒定那些缺乏基因RB的病人,，同時還進行直接組織學(xué)分析。這些病人代表著不同的乳腺癌亞型,，并接受不同用藥方案的治療。
研究人員發(fā)現(xiàn)基因RB缺失與大多數(shù)乳腺癌亞型對所有已研究的新輔助療法的反應(yīng)發(fā)生改善相關(guān)聯(lián),。
總之,，這些數(shù)據(jù)表明基因RB缺失可能是一種有用的生物分子標(biāo)記物來確定對新輔助化療作出更好反應(yīng)的乳腺癌患者?；蜻@些發(fā)現(xiàn),，研究人員已啟動一項前瞻性的臨床試驗以便評估RB和另一種分子標(biāo)記物PTEN與乳腺癌對新輔助化療作出的反應(yīng)之間存在的關(guān)聯(lián)性。(生物谷：Bioon.com)
本文編譯自Breast cancer patients who lack RB gene respond better to neoadjuvant chemotherapy
doi: 10.1158/1078-0432.CCR-12-0903
PMC:
PMID:
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.
