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
{"title":"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。","authors":"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","doi":"10.1007/s10549-025-07749-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Statistically standardized estrogen receptor (ER) and progesterone receptor (PgR) differentiated prognosis. Here we examined statistically standardized human epidermal growth receptor 2 (HER2).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Adjunctive statistical standardization of quantitated adjuvant HER2 and ultra-low HER2 in Canadian Cancer Trials Group MA.27 trial of exemestane versus anastrozole.\",\"authors\":\"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\",\"doi\":\"10.1007/s10549-025-07749-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Statistically standardized estrogen receptor (ER) and progesterone receptor (PgR) differentiated prognosis. Here we examined statistically standardized human epidermal growth receptor 2 (HER2).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":9133,\"journal\":{\"name\":\"Breast Cancer Research and Treatment\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-06-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Breast Cancer Research and Treatment\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10549-025-07749-9\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research and Treatment","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10549-025-07749-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Adjunctive statistical standardization of quantitated adjuvant HER2 and ultra-low HER2 in Canadian Cancer Trials Group MA.27 trial of exemestane versus anastrozole.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
