An AI Model Identifies Chemotherapy Benefit in Node-Negative HR+/HER2- Breast Cancer Patients from TAILORx, a Phase 3 Randomized Clinical Trial
- 1NYU Langone Laura and Isaac Perlmutter Cancer Center New York, NY United States
Abstract
BACKGROUNDThe prescribing of adjuvant chemotherapy for patients with breast cancer must balance the survival benefit against treatment-related toxicities. TAILORx, a phase 3 randomized clinical trial, demonstrated that endocrine therapy alone was, on average, noninferior to chemoendocrine therapy for patients classified as intermediate risk by a 21-gene Recurrence Score (RS) assay. Uncertainty remains about the optimal strategy to identify which intermediate-RS individuals derive benefit from chemotherapy.
METHODSWe analyzed 6735 patients from the TAILORx trial using Ataraxis Breast CTX with pathology images (H&E slides) and RS available. CTX is an AI model which integrates morphologic features extracted from H&E-stained slides with clinical variables to generate individualized predictions of prognosis (CTX-prognostic) and chemotherapy benefit (CTX-benefit). No data from TAILORx were used to train CTX and CTX was not retrained or recalibrated for this study. Analyses were prespecified in a protocol approved by ECOG-ACRIN.
RESULTSAmong patients treated with endocrine therapy alone, CTX-prognostic predicted disease-free interval (DFI), with a hazard ratio per 1 SD increase of 1.651 (95% CI, 1.511-1.803, p < 0.001) and C-index of 0.736 (95% CI, 0.697-0.770). Performance was similar in patients treated with chemoendocrine therapy (hazard ratio = 1.642 [95% CI, 1.495-1.804, p < 0.001], C-index = 0.720 [95% CI, 0.681-0.756]). After adjusting for the RS, CTX-prognostic remained significantly associated with DFI in both treatment groups. In the intermediate-RS subgroup, the treatment-by-biomarker interaction for CTX-benefit was significant (p = 0.016), with patients identified as high-benefit deriving a 5.6% increase in observed 5-year DFI rates from the addition of chemotherapy, compared with no detectable benefit in low-benefit patients. Stratifying the same subgroup by RS at a threshold selecting a similar proportion of patients yielded no significant interaction (p = 0.20).
CONCLUSIONSIn an analysis of TAILORx, CTX-prognostic stratified patients according to their risk of recurrence. Among intermediate-RS patients, CTX-benefit identified who derived clinically meaningful benefit from adjuvant chemotherapy, a population currently not identifiable by the RS alone.
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BibTeX
@misc{chan2026model,
title = {{An AI Model Identifies Chemotherapy Benefit in Node-Negative HR+/HER2- Breast Cancer Patients from TAILORx, a Phase 3 Randomized Clinical Trial}},
author = {N. Chan and C. Tang and D. Biswas and J. Park and K. Zeng and J. Cappadona and C. Liu and A. McMclean and J. Berrevoets and L. Bao and B. Machura and R. J. Gray and V. Wang and J. Witowski and K. J. Geras and J. A. Sparano and TAILORx Investigators},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.12.26362500},
url = {https://www.medrxiv.org/content/10.64898/2026.09.12.26362500v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - An AI Model Identifies Chemotherapy Benefit in Node-Negative HR+/HER2- Breast Cancer Patients from TAILORx, a Phase 3 Randomized Clinical Trial
AU - N. Chan
AU - C. Tang
AU - D. Biswas
AU - J. Park
AU - K. Zeng
AU - J. Cappadona
AU - C. Liu
AU - A. McMclean
AU - J. Berrevoets
AU - L. Bao
AU - B. Machura
AU - R. J. Gray
AU - V. Wang
AU - J. Witowski
AU - K. J. Geras
AU - J. A. Sparano
AU - TAILORx Investigators
PY - 2026
DA - 2026/09/12
PB - medRxiv
DO - 10.64898/2026.09.12.26362500
UR - https://www.medrxiv.org/content/10.64898/2026.09.12.26362500v1
AB - BACKGROUNDThe prescribing of adjuvant chemotherapy for patients with breast cancer must balance the survival benefit against treatment-related toxicities. TAILORx, a phase 3 randomized clinical trial, demonstrated that endocrine therapy alone was, on average, noninferior to chemoendocrine therapy for patients classified as intermediate risk by a 21-gene Recurrence Score (RS) assay. Uncertainty remains about the optimal strategy to identify which intermediate-RS individuals derive benefit from chemotherapy. METHODSWe analyzed 6735 patients from the TAILORx trial using Ataraxis Breast CTX with pathology images (H&E slides) and RS available. CTX is an AI model which integrates morphologic features extracted from H&E-stained slides with clinical variables to generate individualized predictions of prognosis (CTX-prognostic) and chemotherapy benefit (CTX-benefit). No data from TAILORx were used to train CTX and CTX was not retrained or recalibrated for this study. Analyses were prespecified in a protocol approved by ECOG-ACRIN. RESULTSAmong patients treated with endocrine therapy alone, CTX-prognostic predicted disease-free interval (DFI), with a hazard ratio per 1 SD increase of 1.651 (95% CI, 1.511-1.803, p < 0.001) and C-index of 0.736 (95% CI, 0.697-0.770). Performance was similar in patients treated with chemoendocrine therapy (hazard ratio = 1.642 [95% CI, 1.495-1.804, p < 0.001], C-index = 0.720 [95% CI, 0.681-0.756]). After adjusting for the RS, CTX-prognostic remained significantly associated with DFI in both treatment groups. In the intermediate-RS subgroup, the treatment-by-biomarker interaction for CTX-benefit was significant (p = 0.016), with patients identified as high-benefit deriving a 5.6% increase in observed 5-year DFI rates from the addition of chemotherapy, compared with no detectable benefit in low-benefit patients. Stratifying the same subgroup by RS at a threshold selecting a similar proportion of patients yielded no significant interaction (p = 0.20). CONCLUSIONSIn an analysis of TAILORx, CTX-prognostic stratified patients according to their risk of recurrence. Among intermediate-RS patients, CTX-benefit identified who derived clinically meaningful benefit from adjuvant chemotherapy, a population currently not identifiable by the RS alone.
ER -