预测乳腺癌复发的四种多基因检测比较
目前，21基因复发评分、50基因复发风险、8基因内分泌预测、7基因乳腺癌指数等多基因检测已被临床用于推算激素受体阳性HER2阴性早期乳腺癌绝经患者内分泌治疗的远处复发风险，以判断是否需要化疗。不过，各种多基因检测的远处复发风险推算值并不一致。
2020年10月27日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表英国伦敦大学癌症研究院、皇家马斯登医院、伦敦大学玛丽王后学院、格拉斯哥南部综合医院、美国旧金山加利福尼亚大学的ATAC研究转化分析报告，对21基因复发评分、50基因复发风险、8基因内分泌预测、7基因乳腺癌指数预测乳腺癌复发的一致性和分子特征进行了比较。
ATAC (Anastrozole, Tamoxifen Alone or in Combination): A Randomised, Double Blind Trial Comparing Anastrozole Alone With Tamoxifen Alone With Anastrozole and Tamoxifen in Combination, as Adjuvant Treatment in Post-Menopausal Women With Breast Cancer (NCT00849030)
ATAC为多中心随机双盲安慰剂对照研究，于1996年7月12日～2000年3月24日从全球21个国家地区381家医院入组雌激素受体阳性HER2阴性早期乳腺癌术后尚未化疗的绝经女性9366例，按1∶1∶1的比例随机分为3组：阿那曲唑组3125例、他莫昔芬组3116例、阿那曲唑＋他莫昔芬组3125例。本转化分析对ATAC研究他莫昔芬组和阿那曲唑组785例患者的21基因复发评分、50基因复发风险、8基因内分泌预测、7基因乳腺癌指数进行比较，并排除某些检测包含的临床病理特征。21基因复发评分的雌激素、增殖、浸润、HER2指标被用于分析相应分子特征。通过斯皮尔曼等级相关系数和方差分析，对4种多基因检测及其分子特征的一致性和相关性进行比较。
结果，4种多基因分子评分之间的相关性：
21基因复发评分与50基因复发风险的相关性较弱（ρ=0.32）
21基因复发评分与7基因乳腺癌指数的相关性较弱（ρ=0.35）
其余分子评分之间的相关性较强（ρ=0.63～0.74）
21基因复发评分与其雌激素指标成反比（ρ=-0.79），与其增殖指标成正比（ρ=0.36）。
增殖指标占21基因复发评分与50基因复发风险不一致的72.5%，而雌激素指标仅占0.6%。
8基因内分泌预测和7基因乳腺癌指数与21基因复发评分的不一致大部分由增殖指标带来（分别占50.0%和54.3%），而由雌激素指标带来的不一致较小（分别占20.2%和2.7%）。
因此，该研究结果表明，与普遍认知相反，21基因复发评分的雌激素相关特征决定因素较强，而由增殖指标决定因素较弱。不过，8基因内分泌预测、7基因乳腺癌指数、尤其50基因复发风险，大部分取决于增殖特征。这些关系有助于解释4种多基因检测预后作用的不一致。
J Clin Oncol. 2020 Oct 27. Online ahead of print.
Molecular Drivers of Oncotype DX, Prosigna, EndoPredict, and the Breast Cancer Index: A TransATAC Study.
Buus R, Sestak I, Kronenwett R, Ferree S, Schnabel CA, Baehner FL, Mallon EA, Cuzick J, Dowsett M.
The Institute of Cancer Research, London, United Kingdom; Royal Marsden Hospital, London, United Kingdom; Queen Mary University of London, London, United Kingdom; Southern General Hospital, Glasgow, United Kingdom; Myriad International GmbH, Cologne, Germany; NanoString Technologies, Seattle, WA; Biotheranostics, San Diego, CA; Genomic Health, Redwood City, CA; University of California, San Francisco, San Francisco, CA.
PURPOSE: The Oncotype DX Recurrence Score (RS), Prosigna Prediction Analysis of Microarray 50 (PAM50) Risk of Recurrence (ROR), EndoPredict (EP), and Breast Cancer Index (BCI) are used clinically for estimating risk of distant recurrence for patients receiving endocrine therapy. Discordances in estimates occur between them. We aimed to identify the molecular features that drive the tests and lead to these differences.
PATIENTS AND METHODS: Analyses for RS, ROR, EP, and BCI were conducted by the manufacturers in the TransATAC sample collection that consisted of the tamoxifen or anastrozole arms of the ATAC trial. Estrogen receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative cases without chemotherapy treatment were included in which all four tests were available (n = 785). Clinicopathologic features included in some tests were excluded from the comparisons. Estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of variance tests were applied.
RESULTS: There were moderate to strong correlations among the four molecular scores (ρ = 0.63-0.74) except for RS versus ROR (ρ = 0.32) and RS versus BCI (ρ = 0.35). RS had strong negative correlation with its estrogen module (ρ = -0.79) and moderate positive correlation with its proliferation module (ρ = 0.36). RS's proliferation module explained 72.5% of ROR's variance, while the estrogen module explained only 0.6%. Most of EP's and BCI's variation was accounted for by the proliferation module (50.0% and 54.3%, respectively) and much less by the estrogen module (20.2% and 2.7%, respectively).
CONCLUSION: In contrast to common understanding, RSs are determined more strongly by estrogen-related features and only weakly by proliferation markers. However, the EP, BCI, and particularly ROR scores are determined largely by proliferative features. These relationships help to explain the differences in the prognostic performance of the tests.
PMID: 33108242
DOI: 10.1200/JCO.20.00853