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. 2025 Aug 23.
doi: 10.1245/s10434-025-17933-2. Online ahead of print.

Impact of Time to Surgery Post Neoadjuvant Chemotherapy on Breast Cancer Outcomes: A Retrospective Study of Patients Enrolled in the I-SPY 2 Clinical Trial

Julie Van Hassel  1 , Katrina Dimitroff  2 , Christina Yau  2 , Rita Mukhtar  2 , Judy C Boughey  3 , Velle Ladores  2 , Marissa M Howard-McNatt  4 , Nora Jaskowiak  5 , Jane Perlmutter  6 , Angela DeMichele  7 , Douglas Yee  8 , Nola Hylton  2 , W Fraser Symmans  9 , Laura Van't Veer  2 , Hope Rugo  2 , Laura J Esserman  2 , Rebecca Shatsky  10 , Claudine Isaacs  11 , Henry Kuerer  9 , Anne M Wallace  10 , Nicolas Prionas  2 , Jennifer Tseng  12 , Chantal R Reyna  13 , Neil Taunk  7 , Susan Kesmodel  14 , Marie C Lee  15 , Jana Fox  16 , Mara A Piltin  3 , Julia Tchou  7 , Cletus A Arciero  17 , Lauren M Postlewait  17 , Candice Sauder  18 , Roshni Rao  19
Affiliations

Impact of Time to Surgery Post Neoadjuvant Chemotherapy on Breast Cancer Outcomes: A Retrospective Study of Patients Enrolled in the I-SPY 2 Clinical Trial

Julie Van Hassel et al. Ann Surg Oncol. .

Abstract

Background: Neoadjuvant chemotherapy (NAC) is widely used to treat high-risk breast cancer. However, the optimal time to surgery (TTS) following NAC remains undefined. This study investigates the impact of TTS on oncologic outcomes using the I-SPY 2 Trial cohort.

Methods: A retrospective analysis of 1877 patients with breast cancer enrolled in the I-SPY 2 Trial was performed. Patients were grouped by TTS post-NAC: 1-4 weeks, 5 weeks, 6-8 weeks, and 9 + weeks. Baseline demographic, clinical, imaging, and treatment response data were collected. Event-free survival (EFS) and local recurrence-free interval (LRFI) were evaluated using Kaplan-Meier analyses and Cox models. Subgroup analyses were performed by tumor receptor subtypes (hormone receptor [HR]+ human epidermal growth factor receptor 2 [HER2]-, HER2 +, and triple-negative breast cancer [TNBC]) and residual cancer burden (RCB) class.

Results: Among 1877 patients, 526 (28.0%) underwent surgery between 1-4 weeks, 425 (22.6%) at 5 weeks, 490 (26.1%) between 6-8 weeks, and 436 (23.2%) at 9+ weeks post-NAC. Prolonged TTS was associated with worse 5-year EFS and LRFI on Kaplan-Meier analysis (p < 0.001 for both). Delays particularly affected outcomes in patients with HR+/HER2- and TNBC tumors. In patients with RCB class II/III, a TTS of 9+ weeks was independently associated with worse EFS (hazard ratio [HR] 2.04, p = 0.001) and LRFI (HR 2.77, p = 0.005). Conversely, in patients with a pathologic complete response/RCB class I, delayed surgery did not significantly impact outcomes.

Conclusions: TTS of 9+ weeks following NAC is independently associated with worse oncologic outcomes, especially in patients with TNBC and HR+/HER2- tumors and high residual disease.

Keywords: Breast cancer; Neoadjuvant chemotherapy; Oncologic outcomes; Residual cancer burden; Time to surgery.

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Conflict of interest statement

Disclosure: Judy C. Boughey receives institutional research funding from Eli Lilly, SimBioSys, and Quantum Leap Healthcare, and serves on the Data Safety Monitoring Board for Cairn Surgical. Angela DeMichele reports institutional research funding from Novartis, Pfizer, Genentech, and Neogenomics, and serves as Program Chair for the Scientific Advisory Committee at the American Society for Clinical Oncology. Douglas Yee reports research funding fromNIH/NCI P30 CA077598, P01 CA234228-01, and R01CA251600; consulting fees from Martell Diagnostics; and honoraria and travel for speaking at the International Breast Cancer Conference. Nola Hylton reports institutional research funding from the NIH. W. Fraser Symmans reports shares from IONIS Pharmaceuticals and Eiger Biopharmaceuticals; has received consulting fees from AstraZeneca; is a co-founder of and has equity in Delphi Diagnostics; and has issued patents for (1) a method to calculate residual cancer burden, and (2) genomic signature to measure sensitivity to endocrine therapy. Laura van’t Veer is a founding advisor and shareholder of Exai Bio, and is a part-time employee of and owns stock in Agendia. Hope Rugo reports institutional research support from AstraZeneca, Daiichi Sankyo, Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Gilead Sciences, Inc., Lilly, Merck & Co., Novartis Pharmaceuticals Corporation, Pfizer, Stemline Therapeutics, OBI Pharma, Ambrx, and Greenwich Pharma, and advisory and consulting roles with Chugai, Puma, Sanofi, Napo, and Mylan. MD reports research grants from the NIH/NCI and NIH/NIA, and contracts from the Patient-Centered Outcomes Research Institute. Laura J. Esserman reports participation on the Blue Cross Medical Advisory Panel, and is an uncompensated board member of Quantum Leap Healthcare Collaborative. Rebecca Shatsky reports institutional research funding from OBI Pharmaceuticals, Quantum Leap Healthcare Collaborative, AstraZeneca, and Gilead; serves on the AstraZeneca and Stemline Advisory Boards and the Gilead Speaker’s Bureau; and reports a consultancy role with Quantum Leap Healthcare Collaborative. Claudine Isaacs reports institutional research funding from Tesaro/GSK, Seattle Genetics, Pfizer, AstraZeneca, BMS, Genentech, Novartis, and Regeneron; consultancy roles with AstraZeneca, Genentech, Gilead, ION, Merck, Medscape, MJH Holdings, Novartis, Pfizer, PUMA, and Seagen; and royalties from Wolters Kluwer (UptoDate) and McGraw Hill (Goodman and Gillman). Julie Van Hassel, Katrina Dimitroff, Christina Yau, Rita Mukhtar, Velle Ladores, Marissa M. Howard-McNatt, Nora Jaskowiak, Jane Perlmutter, Henry Kuerer, Anne M. Wallace, Nicolas Prionas, Jennifer Tseng, Chantal R. Reyna, Neil Taunk, Susan Kesmodel, Marie C. Lee, Jana Fox, Mara A. Piltin, Julia Tchou, Cletus A. Arciero, Lauren M. Postlewait, Candice Sauder, and Roshni Rao declare no competing interests that may be relevant to the contents of this study.

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