Adjunctive statistical standardization of quantitated adjuvant HER2 and ultra-low HER2 in Canadian Cancer Trials Group MA.27 trial of exemestane versus anastrozole.

IF 3 3区医学 Q2 ONCOLOGY

Breast Cancer Research and Treatment Pub Date : 2025-06-23 DOI:10.1007/s10549-025-07749-9

Judith-Anne W Chapman, Jane Bayani, Sandip SenGupta, John M S Bartlett, Tammy Piper, Mary Anne Quintayo, Shakeel Virk, Paul E Goss, James N Ingle, Matthew J Ellis, George W Sledge, G Thomas Budd, Manuela Rabaglio, Rafat H Ansari, Richard Tozer, David P D'Souza, Haji Chalchal, Silvana Spadafora, Vered Stearns, Edith A Perez, Karen A Gelmon, Timothy J Whelan, Catherine Elliott, Lois E Shepherd, Bingshu E Chen, Karen J Taylor

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引用次数: 0

Abstract

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.

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加拿大癌症试验组MA.27依西美坦与阿那曲唑试验中定量佐剂HER2和超低HER2的辅助统计学标准化。

目的：统计标准化雌激素受体（ER）和孕激素受体（PgR）的鉴别预后。在这里，我们检查了统计学标准化的人表皮生长受体2 （HER2）。方法：CCTG MA.27 （NCT00066573）是一项依西美坦与阿那曲唑在绝经后ER +和/或PgR +肿瘤妇女中的辅助III期试验。我们集中定量了机器图像免疫组化HER2，定义了美国临床肿瘤学会(ASCO)/美国病理学家学会（CAP）双探针FISH HER2/CEP17分类，确定了超低HER2 （IHC为0，（0,10%）1 +染色），并将HER2标准化为平均值0，标准差1。采用Kaplan-Meier图描述单变量远端无病生存（DDFS），并采用Wilcoxon （Peto-Prentice）检验统计量进行检验。校正Cox多变量回归双侧Wald检验具有名义显著性p结果：在7576名女性中，2900名有ER结果；2726年,PgR;2680年,HER2;2325， ER/PgR/HER2用于多变量调查。ASCO/CAP分类对单变量DDFS有显著差异（p = 0.01），但对IHC 0 （N = 864）和超低HER2 （N = 1143）没有显著差异。统计标准化对单变量DDFS无差异（p = 0.08-0.27）；然而,(自然对数)标准化值≤1.0(超低1 + / 2 + 3 + HSCORE或% + 1.0 (HSCORE > 19;% + > 14)。在PgR模型中，ASCO/CAP、统计学标准化、ER （p = 0.65-0.94）或HER2 （p = 0.20-0.97）与DDFS均无相关性；PgR越高，DDFS越好（p≤0.003）。结论：ASCO/CAP分类对DDFS有显著差异，而统计学标准化无显著差异。超低HER2和IHC 0无染色患者5年DDFS相似，而标准化显示极低1 + /2 + /3 +和最高HER2染色患者预后相似。由于HER2检测的动态范围，我们在评估超低或极低HER2时要谨慎。

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来源期刊

Breast Cancer Research and Treatment 医学-肿瘤学

CiteScore

6.80

自引率

2.60%

发文量

342

审稿时长

1 months

期刊介绍： Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.