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Clinical Trial
. 2025 May 1;117(5):889-897.
doi: 10.1093/jnci/djae314.

Race and clinical outcomes in hormone receptor-positive, HER2-negative, node-positive breast cancer in the randomized RxPONDER trial

Yara Abdou  1 , William E Barlow  2 , Julie R Gralow  3 , Funda Meric-Bernstam  4 , Kathy S Albain  5 , Daniel F Hayes  6 , Nancy U Lin  7 , Edith A Perez  8 , Lori J Goldstein  9 , Stephen K L Chia  10 , Sukhbinder Dhesy-Thind  11 , Priya Rastogi  12 , Emilio Alba  13 , Suzette Delaloge  14 , Anne F Schott  6 , Steven Shak  15 , Priyanka Sharma  16 , Danika L Lew  2   17 , Jieling Miao  2   17 , Joseph M Unger  2   17 , Debasish Tripathy  4 , Gabriel N Hortobagyi  4 , Lajos Pusztai  18 , Kevin Kalinsky  19
Affiliations
Clinical Trial

Race and clinical outcomes in hormone receptor-positive, HER2-negative, node-positive breast cancer in the randomized RxPONDER trial

Yara Abdou et al. J Natl Cancer Inst. .

Abstract

Background: The phase III RxPONDER trial has affected treatment for node-positive (1-3), hormone receptor-positive, HER2-negative breast cancer with a 21-gene recurrence score (RS) less than 26. We investigated how these findings apply to different racial and ethnic groups within the trial.

Methods: The trial randomly assigned women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS), with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathological characteristics, RS, and treatment.

Results: A total of 4048 women with self-reported race/ethnicity were included: Hispanic (15.1%), non-Hispanic Black (NHB) (6.1%), Native American/Pacific Islander (0.8%), Asian (8.0%), and non-Hispanic White (NHW) (70%). No differences in RS distribution, tumor size, or number of positive nodes were observed by race/ethnicity. Relative to NHWs, IDFS was worse for NHB participants (5-year IDFS 91.6% vs 87.1%, HR = 1.37; 95% CI = 1.03 to 1.81) and better for Asians (91.6% vs 93.9%, HR = 0.64; 95% CI = 0.46 to 0.91). Relative to NHW, DRFS was worse for NHB participants (5-year DRFS 95.8% vs 91.0%, HR = 1.65; 95% CI = 1.17 to 2.32) and better for Asians (95.8% vs 96.7%, HR = 0.59; 95% CI = 0.37 to 0.95). Adjusting for clinical characteristics, particularly body mass index, diminished the effect of race on outcomes. Chemotherapy treatment efficacy did not differ by race/ethnicity.

Conclusions: NHB women had worse clinical outcomes compared with NHWs in the RxPONDER trial despite similar RS and comparable treatment. Our study emphasizes the persistent racial disparities in breast cancer outcomes while highlighting complex interactions among contributing factors.

Trial registration: ClinicalTrials.gov: NCT01272037.

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Conflict of interest statement

Dr Abdou reported consulting fees from Exact Sciences and AstraZeneca outside the submitted work. Dr Meric-Bernstam reported consulting fees from AbbVie, AstraZeneca Pharmaceuticals, Becton Dickinson, Calibr (a division of Scripps Research), Daiichi Sankyo, EcoR1 Capital, eFFECTOR Therapeutics, Exelixis, GT Aperion, t Incyte, Infinity Pharmaceuticals, Jazz Pharmaceuticals, LegoChem Biosciences, Lengo Therapeutics, Menarini Group, Molecular Templates, Protai Bio, Roche, Tallac Therapeutics, Zymeworks, advisory committee for Black Diamond Therapeutics, Biovica, Eisai Medical Research, FogPharma, Harbinger Health, Karyopharm Therapeutics, LOXO-Oncology Mersana Therapeutics, OnCusp Therapeutics, Sanofi Pharmaceuticals, Seagen, Theratechnologies, Zentalis Pharmaceuticals, sponsored research to the institution from Jazz Pharmaceuticals, Zymeworks, Aileron Therapeutics, Inc, AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc, Curis Inc, CytomX Therapeutics Inc, Daiichi Sankyo Co. Ltd, Debiopharm International, eFFECTOR Therapeutics, Genentech Inc, Guardant Health Inc, Klus Pharma, Takeda Pharmaceutical, Novartis, Puma Biotechnology Inc, Taiho Pharmaceutical Co, honoraria from Dava Oncology, and travel support from European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO), Cholangiocarcinoma Foundation, Dava Oncology, all outside the submitted work. Dr Albain reports advisory/consulting fees from Exact Sciences (previously Genomic Health, Inc), SeaGen, Agendia, and research funding from QuantumLeap Healthcare, all outside the submitted work. Dr Hayes reported consulting fees from Artera.ai, Arvenis, BioVeca, BioTheranostics an Hologic Company, Cellworks, Centrix, Cepheid, Delphi Diagnostics, EPIC Sciences, EXACT Sciences, Freenome, Guardant, Macrogenics, Oncocyte, Stratipath, Tempus, Turnstone Biologics, and Xilis, research support to the institution from Astra Zeneca, Menarini Silicon Biosystems, Pfizer, Cepheid, and Angle, stock options from InBiomotion, Xilis, and CellWorks, honoraria from UpToDate and CancerExpertNow, and the University of Michigan holds a patent for which Dr Hayes is the named investigator and which was licensed to Menarini Silicon Biosystems from whom Dr Hayes received annual royalties ending January 1, 2022, all outside the submitted work. Dr Lin reported research Institutional funding from Genentech, Pfizer, Merck, Seattle Genetics, Zion Pharmaceuticals, Olema Pharmaceuticals, and AstraZeneca, consulting fees from Seattle Genetics, Daichii-Sankyo, AstraZeneca, Olema Pharmaceuticals, Janssen, Blueprint Medicines, Stemline/Menarini, Artera Inc, and Eisai, and travel support (outside consulting fees) from Olema Pharmaceuticals, all outside the submitted work. Dr Chia reported advisory fees from Novartis, Hoffmann LaRoche, Pfizer, Eli Lilly, AstraZeneca, Gilead, Merck, and Daiichi Sankyo, all outside the submitted work. Dr Dhesy-Thind reported consulting fees from Novartis Canada Pharmaceuticals Inc; Seagen and honoraria from Pfizer Canada; Novartis Canada Pharmaceuticals Inc, outside the submitted work. Dr Delaloge reported institutional grants from Pfizer, Novartis, AstraZeneca, Roche, Lilly, Orion, Amgen, Sanofi, BMS, Pierre Fabre, Taiho, European Commission, and French Government, travel support from Novartis, Roche, and Seagen, and advisory fees to the institution from BIG international group, Pfizer, Gilead, Sanofi, Elsan, Besins, Decibio, AstraZeneca, all outside the submitted work. Dr Shak reported consulting fees from Exact Sciences, N-Power Medicine, and Genomic Life, all outside submitted work. Dr Sharma reported research funding from Merck, Novartis, Gilead, and Bristol Myers Squibb, royalties from UpToDate, and consulting fees from Merck, Gilead, Genzyme Corporation (Sanofi), Novartis, AstraZeneca, GSK, Pfizer, and Exact Sciences, all outside the submitted work. Dr Unger reported consulting fees from AstraZeneca, outside the submitted work. Dr Tripathy reported consulting fees from Novartis, Pfizer, GlaxoSmithKline, Genomic Heath, AstraZeneca, Oncopep, Sermonix, Personalis, Ambrx, Gilead, Roche, Menarini, and Jazz Pharmaceuticals, institutional research support from Novartis, Polyphor, Pfizer, and Ambrx, and travel support from Novartis and AstraZeneca, all outside the submitted work. Dr Pusztai reported consulting fees and honoraria for advisory board participation from Pfizer, Astra Zeneca, Merck, Novartis, Bristol-Myers Squibb, Stemline-Menarini, GlaxoSmithKline, Genentech/Roche, Personalis, Daiichi, Natera, Agendia, and Exact Sciences and institutional research funding from Menarini, AstraZeneca, Merck, Pfizer, and Bristol Myers Squibb, all outside the submitted work. Dr Kalinsky reported the following: Spouse, Stock: EQRX (Prior Employee), ADC Therapeutics, consulting fees from Lilly, Novartis, Genentech/Roche, Gilead, Seattle Genetics, Astra Zeneca, Daiichi Sankyo, Puma Biotechnology, Mersana, Menarini Silicon Biosystems, Myovant Sciences, Takeda, Prelude Therapeutics, eFFECTOR Therapeutis, Regor, RayzeBio, Relay Therapuetics, Merck, and Institutional funding from Novartis, Genentech/Roche, Lilly, Seattle Genetics, Astra Zeneca, Daichi Sankyo, Ascentage, all outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.
Distribution of recurrence scores by race and ethnicity. Box plots show the median (center line) and the 75th and 25th percentiles (top and bottom of the box, respectively). The hash marks at the top and bottom show the normalized range for recurrence score based on its distribution. Outliers are indicated by dots outside this range. NAPI = Native American/Pacific Islander.
Figure 2.
Figure 2.
Invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) among participants according to race and ethnicity. Figure 2, A shows IDFS, whereas Figure 2, B shows DRFS. The Kaplan-Meier estimate at 5 years is also reported in the legend. All Kaplan-Meier figures are unadjusted for other factors.
Figure 3.
Figure 3.
Invasive disease-free survival (IDFS) among participants according to non-Hispanic White or Black race and by randomized treatment arm. Figure 3, A shows IDFS for postmenopausal participants, whereas Figure 3, B shows IDFS for premenopausal participants. Randomized treatment is either CET (chemotherapy followed by endocrine therapy) or ET (endocrine therapy only). The Kaplan-Meier estimate at 5 years is also reported in the legend. All Kaplan-Meier figures are unadjusted for other factors.
See this image and copyright information in PMC

References

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    1. Office of the Commissioner. Collection of Race and Ethnicity Data in Clinical Trials. Updated Thu, 08/10/2023—16:04.

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