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; 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:10.1200/JCO.24.00835

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, 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 PerezKaren A Gelmon, Timothy J Whelan, Catherine Elliott, Lois E Shepherd, Bingshu E Chen, Karen J Taylor

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	JCO2400835
Journal	Journal of Clinical Oncology
DOIs	https://doi.org/10.1200/JCO.24.00835 https://doi.org/10.1200/jco.24.00835
Publication status	Published - 2 Jun 2024

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JCO.24.00835_R1
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Chapman, J.-A. W., Bayani, J., SenGupta, S., Bartlett, J. M. S., Piper, T., Quintayo, M. A., Virk, S., Goss, P. E., Ingle, J. N., Ellis, M. J., Sledge, G. W., Budd, G. T., Rabaglio, M., Ansari, R. H., Tozer, R., D'Souza, D. P., Chalchal, H., Spadafora, S., Stearns, V., ... Taylor, K. J. (2024). 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. Journal of Clinical Oncology, JCO2400835. https://doi.org/10.1200/JCO.24.00835, https://doi.org/10.1200/jco.24.00835

@article{1403d17603c64ab0ad50d22c00fe57b8,

title = "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",

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.",

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

year = "2024",

month = jun,

day = "2",

doi = "10.1200/JCO.24.00835",

language = "English",

pages = "JCO2400835",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

}

Chapman, J-AW, Bayani, J, SenGupta, S, Bartlett, JMS, Piper, T, Quintayo, MA, Virk, S, Goss, PE, Ingle, JN, Ellis, MJ, Sledge, GW, Budd, GT, Rabaglio, M, Ansari, RH, Tozer, R, D'Souza, DP, Chalchal, H, Spadafora, S, Stearns, V, Perez, EA, Gelmon, KA, Whelan, TJ, Elliott, C, Shepherd, LE, Chen, BE & Taylor, KJ 2024, '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', Journal of Clinical Oncology, pp. JCO2400835. https://doi.org/10.1200/JCO.24.00835, https://doi.org/10.1200/jco.24.00835

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. / Chapman, Judith-Anne W; Bayani, Jane; SenGupta, Sandip et al.
In: Journal of Clinical Oncology, 02.06.2024, p. JCO2400835.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Chapman, Judith-Anne W

AU - Bayani, Jane

AU - SenGupta, Sandip

AU - Bartlett, John M S

AU - Piper, Tammy

AU - Quintayo, Mary Anne

AU - Virk, Shakeel

AU - Goss, Paul E

AU - Ingle, James N

AU - Ellis, Matthew J

AU - Sledge, George W

AU - Budd, G Thomas

AU - Rabaglio, Manuela

AU - Ansari, Rafat H

AU - Tozer, Richard

AU - D'Souza, David P

AU - Chalchal, Haji

AU - Spadafora, Silvana

AU - Stearns, Vered

AU - Perez, Edith A

AU - Gelmon, Karen A

AU - Whelan, Timothy J

AU - Elliott, Catherine

AU - Shepherd, Lois E

AU - Chen, Bingshu E

AU - Taylor, Karen J

PY - 2024/6/2

Y1 - 2024/6/2

N2 - 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.

AB - 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.

U2 - 10.1200/JCO.24.00835

DO - 10.1200/JCO.24.00835

M3 - Article

C2 - 38824432

SN - 0732-183X

SP - JCO2400835

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

ER -

Chapman JAW, Bayani J, SenGupta S, Bartlett JMS, Piper T, Quintayo MA et al. 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. Journal of Clinical Oncology. 2024 Jun 2;JCO2400835. doi: 10.1200/JCO.24.00835, 10.1200/jco.24.00835

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

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