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Clinical Trial
. 2024 Aug 20;42(24):2887-2898.
doi: 10.1200/JCO.24.00835. Epub 2024 Jun 2.

Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole

Judith-Anne W Chapman  1 , Jane Bayani  2   3 , Sandip SenGupta  4 , John M S Bartlett  5 , Tammy Piper  5 , Mary Anne Quintayo  2 , Shakeel Virk  6 , Paul E Goss  7 , James N Ingle  7 , Matthew J Ellis  8 , George W Sledge  9 , G Thomas Budd  10 , Manuela Rabaglio  11 , Rafat H Ansari  12 , Richard Tozer  13 , David P D'Souza  14 , Haji Chalchal  15 , Silvana Spadafora  16 , Vered Stearns  17 , Edith A Perez  7   18 , Karen A Gelmon  19 , Timothy J Whelan  13 , Catherine Elliott  6 , Lois E Shepherd  6 , Bingshu E Chen  6 , Karen J Taylor  5
Affiliations
Clinical Trial

Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole

Judith-Anne W Chapman et al. J Clin Oncol. .

Abstract

Purpose: ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated positivity could indicate differential associations of positivity with breast cancer outcomes.

Methods: MA.27 (ClinicalTrials.gov identifier: NCT00066573) was a phase III adjuvant trial of exemestane versus anastrozole in postmenopausal women with early-stage breast cancer. Immunochemistry ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation and statistically standardized to mean 0 and standard deviation (SD) 1 after Box-Cox variance stabilization transformations of square for ER; for PgR, (1) natural logarithm (0.1 added to 0 HSCOREs and 0%+) and (2) square root. Our primary end point was MA.27 distant disease-free survival (DDFS) at a median 4.1-year follow-up, and secondary end point was event-free survival (EFS). Univariate survival with cut points at SDs about a mean of 0 (≤-1; (-1, 0]; (0, 1]; >1) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions had two-sided Wald tests and nominal significance P < .05.

Results: Of 7,576 women accrued, 3,048 women's tumors had machine-quantitated image analysis results: 2,900 (95%) for ER, 2,726 (89%) for PgR, and 2,582 (85% of 3,048) with both ER and PgR. Higher statistically standardized ER and PgR HSCORE and %+ were associated with better univariate DDFS and EFS (P < .001). In multivariable assessments, ER HSCORE and %+ were not significantly associated (P = .52-.88) with DDFS in models with PgR, whereas higher PgR HSCORE and %+ were significantly associated with better DDFS (P = .001) in models with ER.

Conclusion: Adjunctive statistical standardization differentiated quantitated levels of ER and PgR. Patients with higher ER- and PgR-standardized units had superior DDFS compared with those with HSCOREs and %+ ≤-1.

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