在加拿大癌症试验组MA.27依西美坦与阿那曲唑对比试验中，对定量辅助性人表皮生长因子受体2（HER2）和超低HER2进行辅助性统计标准化。
Adjunctive statistical standardization of quantitated adjuvant HER2 and ultra-low HER2 in Canadian Cancer Trials Group MA.27 trial of exemestane versus anastrozole.
作者信息
Chapman Judith-Anne W, Bayani Jane, SenGupta Sandip, Bartlett John M S, Piper Tammy, Quintayo Mary Anne, Virk Shakeel, Goss Paul E, Ingle James N, Ellis Matthew J, Sledge George W, Budd G Thomas, Rabaglio Manuela, Ansari Rafat H, Tozer Richard, D'Souza David P, Chalchal Haji, Spadafora Silvana, Stearns Vered, Perez Edith A, Gelmon Karen A, Whelan Timothy J, Elliott Catherine, Shepherd Lois E, Chen Bingshu E, Taylor Karen J
机构信息
Canadian Cancer Trials Group Queen's University, 11 Dayman Court, Kitchener, ON, N2M 3A1, Canada.
Ontario Institute for Cancer Research, Toronto, Canada.
出版信息
Breast Cancer Res Treat. 2025 Jun 23. doi: 10.1007/s10549-025-07749-9.
PURPOSE
Statistically standardized estrogen receptor (ER) and progesterone receptor (PgR) differentiated prognosis. Here we examined statistically standardized human epidermal growth receptor 2 (HER2).
METHODS
CCTG MA.27 (NCT00066573) was an adjuvant phase III trial of exemestane versus anastrozole in postmenopausal women with ER + and/or PgR + tumors. We centrally quantitated machine-image immunohistochemical HER2, defined American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) dual-probe FISH HER2/CEP17 categories, determined ultra-low HER2 (IHC 0 with (0,10%] 1 + stain), and standardized HER2 to mean 0, standard deviation 1. Univariate distant disease-free survival (DDFS) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions 2-sided Wald tests had nominal significance p < 0.05.
RESULTS
Of 7576 women, 2900 had ER results; 2726, PgR; 2680, HER2; and 2325, ER/PgR/HER2 for multivariable investigations. ASCO/CAP categorization significantly differentiated univariate DDFS (p = 0.01), although not values of IHC 0 (N = 864) and ultra-low HER2 (N = 1143). Statistical standardization did not differentiate univariate DDFS (p = 0.08-0.27); however, (natural logarithm-) standardized values ≤ - 1.0 (ultra-low 1 + /2 + /3 + HSCORE, or % + , < 0.1) were similar to > 1.0 (HSCORE > 19; % + > 14). Neither ASCO/CAP, nor statistically standardized, ER (p = 0.65-0.94) or HER2 (p = 0.20-0.97) were associated with DDFS in models with PgR; higher PgR had better DDFS (p ≤ .003).
CONCLUSIONS
ASCO/CAP categories significantly differentiated DDFS, while statistical standardization did not. Patients with ultra-low HER2 and IHC 0 without stain had similar 5-year DDFS, while standardization indicated similar prognosis for very low 1 + /2 + /3 + and highest HER2 stain. We caution about assessment of ultra-low, or very low, HER2 due to HER2 assay dynamic range.
目的
经统计学标准化后的雌激素受体（ER）和孕激素受体（PgR）可区分预后。在此，我们对经统计学标准化后的人表皮生长因子受体2（HER2）进行了研究。
方法
CCTG MA.27（NCT00066573）是一项在绝经后ER +和/或PgR +肿瘤女性中比较依西美坦与阿那曲唑的辅助性III期试验。我们集中对机器图像免疫组化HER2进行定量，定义美国临床肿瘤学会（ASCO）/美国病理学家学会（CAP）双探针FISH HER2/CEP17分类，确定超低HER2（免疫组化0且（0,10%]为1 +染色），并将HER2标准化为均值0、标准差1。用Kaplan-Meier图描述单变量远处无病生存期（DDFS），并用Wilcoxon（Peto-Prentice）检验统计量进行检验。调整后的Cox多变量回归双侧Wald检验的名义显著性p < 0.05。
结果
7576名女性中，2900名有ER结果；2726名有PgR结果；2680名有HER2结果；2325名有ER/PgR/HER2结果用于多变量研究。ASCO/CAP分类显著区分单变量DDFS（p = 0.01），尽管免疫组化0（n = 864）和超低HER2（n = 1143）的值无差异。统计学标准化未区分单变量DDFS（p = 0.08 - 0.27）；然而，（自然对数）标准化值≤ -1.0（超低1 + /2 + /3 + HSCORE，或% +，< 0.1）与> 1.0（HSCORE > 19；% + > 14）相似。在有PgR的模型中，ASCO/CAP分类和统计学标准化后的ER（p = 0.65 - 0.94）或HER2（p = 0.20 - 0.97）均与DDFS无关；较高的PgR有更好的DDFS（p≤0.003）。
结论
ASCO/CAP分类显著区分DDFS，而统计学标准化则不然。超低HER2和免疫组化0且无染色的患者5年DDFS相似，而标准化表明极低1 + /2 + /3 +和最高HER2染色的预后相似。由于HER2检测的动态范围，我们对超低或极低HER2的评估持谨慎态度。
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