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. 2025 Apr 1;131(7):e35817.
doi: 10.1002/cncr.35817.

Correlation analysis of invasive disease-free survival and overall survival in a real-world population of patients with HR+/HER2- early breast cancer

Stephanie L Graff  1 , Sara M Tolaney  2 , Lowell L Hart  3   4 , Pedram Razavi  5 , Wolfgang Janni  6 , Lee S Schwartzberg  7 , Andriy Danyliv  8 , Murat Akdere  8 , Ilia Ferrusi  9 , Rishi Rajat Adhikary  10 , Joyce A O'Shaughnessy  11
Affiliations

Correlation analysis of invasive disease-free survival and overall survival in a real-world population of patients with HR+/HER2- early breast cancer

Stephanie L Graff et al. Cancer. .

Abstract

Background: Overall survival (OS) is the gold standard for assessing clinical benefit in oncology but requires extended follow-up to detect sufficient events. Invasive disease-free survival (iDFS) requires shorter follow-up times and is considered an objective and clinically meaningful end point in early breast cancer (EBC) trials. The authors assessed iDFS as a surrogate end point for OS in adjuvant HR+/HER2- EBC using real-world patient-level data.

Methods: A retrospective analysis was conducted on patient data from the ConcertAI Patient360 database (January 1995-April 2021). Key inclusion criteria: age ≥18 years, stage II or III (AJCC 8th Edition) HR+/HER2- EBC, prior surgery, adjuvant endocrine therapy (ET). Spearman ρ, iterative multiple imputation ρ (IMI; 0.8-1 considered "very strong"), and R2 (clinical relevance R2 ≥ 0.70) were used to assess iDFS-OS relationship. Subgroup analyses included ET (nonsteroidal aromatase inhibitor or tamoxifen), stage, menopausal status, nodal status, prior (neo)adjuvant chemotherapy, and prior radiotherapy.

Results: A total of 3133 patients were included (1103 [35.2%] iDFS events; 554 [17.7%] OS events); mean age was 58.4 years, 98.8% were female, 29.9% were premenopausal, and 80.9% had stage II disease. Median follow-up time was 55.1 months. iDFS and OS exhibited a positive, very strong, clinically relevant correlation (Spearman ρ: 0.88 [0.87-0.89]; IMI ρ: 0.83 [0.79-0.86]; both p < .0001). iDFS accounted for 82% of variation in OS (R2 = 0.82). Results of all subgroup analyses were consistent with overall population.

Conclusions: This patient-level real-world analysis demonstrated very strong, positive correlations between iDFS and OS, supporting the use of iDFS as a reliable primary end point in adjuvant HR+/HER2- EBC.

Keywords: HR+/HER2– early breast cancer; correlation analysis; invasive disease‐free survival; overall survival; real world.

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Conflict of interest statement

Stephanie L. Graff reports personal fees from Novartis, Pfizer, AstraZeneca, Genentech, Lilly, Daiichi Sankyo, Gilead Sciences, The Academy for Healthcare Learning, DAVA Oncology, MJH Life Sciences, WebMD/Medscape, IntegrityCE, MedPage Today, MedIQ, Medical Educator Consortium, and Research to Practice; stock ownership from HCA Healthcare; and research grants to institution from Daiichi Sankyo, Novartis, and AstraZeneca. Sara M. Tolaney reports grant funding to institution and personal fees from Eli Lilly, Novartis, AstraZeneca, Merck, Pfizer, Genentech/Roche, Bristol Myers Squibb, Eisai, Sanofi, Daiichi Sankyo, Gilead, Jazz Pharmaceuticals, and Menarini/Stemline; grant funding to institution from Exelixis, NanoString, and OncoPep; and personal fees from Seagen, Arvinas, Cullinan Oncology, eFFECTOR, CytomX, Sumitovant Biopharma, Natera, Tango Therapeutics, SystImmune, Hengrui USA, Blueprint Medicines, Reveal Genomics, Umoja Biopharma, Zentalis, Zymeworks, Circle Pharma, Bayer, Incyte Corp, and Aadi Bioscience. Lowell L. Hart reports grants to institution and personal fees from Novartis. Pedram Razavi reports institutional grants from Grail/Illumina, Novartis, AstraZeneca, Epic Sciences, Invitae/ArcherDX, Tempus, Inivata, and Biotheranostics; and personal fees from Novartis, AstraZeneca, Epic Sciences, Tempus, Inivata, Foundation Medicine, Pfizer, Daiichi Sankyo, Natera, Odyssey Biosciences, Paige.AI, and SAGA Diagnostics. Wolfgang Janni reports personal fees from Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, and Gilead; employment from Universitätsklinikum Ulm; speaker fees to institution from Novartis, GSK, Sanofi, Amgen, Roche, and Lilly; and serves as chair of AGO Breast Council. Lee S. Schwartzberg reports personal fees from AstraZeneca, Daiichi Sankyo, Genentech, Novartis, Pfizer, Seagen, Merck, Spectrum, Napo, and Amgen. Andriy Danyliv reports employment and stock ownership from Novartis. Murat Akdere reports employment and stock ownership from Novartis. Ilia Ferrusi reports employment and stock ownership from Novartis. Rishi Rajat Adhikary reports employment from Novartis. Joyce A. O’Shaughnessy reports personal fees from AbbVie, Agendia, Amgen, Aptitude, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunome, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Odonate Therapeutics, Pfizer, Puma, Prime, Roche, Seagen, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre, Samsung, and Sanofi.

Figures

FIGURE 1
FIGURE 1
Patient attrition flow diagram. BC indicates breast cancer; EBC, early breast cancer; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2.
FIGURE 2
FIGURE 2
iDFS‐OS correlation: overall cohort. iDFS indicates invasive disease‐free survival; IMI, iterative multiple imputation; OS, overall survival.
See this image and copyright information in PMC

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