Abstract PS18-01: Stage Advancement and The Rate of Growth Associated with Preoperative Delay in Patients Having Breast Cancer
Authors: Bleicher Richard , Ruth Karen , Williams Austin , Ross Eric , Porpiglia Andrea , Aggon Allison , Pronovost Mary , Holmes Dennis 
Published: May 2024

Abstract
Introduction:
For every delay interval between breast cancer diagnosis and surgery we have previously found a relative decline in disease-specific survival of 26% (60 d) and overall survival of 9-10% (30 d). There is, however, little explanation for this. In our experience, patients focus on the likelihood of cancer growth between diagnosis and surgery, and whether preoperative delay might lead to upstaging, with nodal status of particular concern when they are clinically node-negative. With little published data about delay-associated upstaging and no large-scale national data determining how fast tumors grow, this study was performed to determine these rates.
Methods:
Patients ≥18 years old having stage 0-III breast cancer who received surgery as first treatment between 2010 and 2020 were reviewed in the National Cancer Database (NCDB), the largest national dataset to contain the needed clinical and pathologic staging. Patients were reviewed for correlation between preoperative delay and cancer upstaging, defined as an increase from cT to pT or cN to pN stages, after assessing baseline clinical stage inaccuracy. Accuracy of clinical staging was determined by comparing clinical stages at presentation to pathologic stages at surgeries ≤15 days of diagnosis, assuming negligible tumor growth in that period. cN3 and cT3 tumors were excluded as there is no higher size-dependent pathologic stage. Upstaging probabilities and odds ratios (ORs) were estimated with logistic regression, adjusted for age, race, Hispanic ethnicity, gender, histology, grade, phenotype, and clinical T or N stage. For patients with delays &gt;15 days, adjusted linear regression coefficients of tumor size on preoperative delay were used to estimate primary invasive tumor growth rates.
Results:
Among 1,040,197 patients, the median time between diagnosis and surgery was 34 days (IQR 23-49), with 11.6% having primary tumoral and 14.6% having nodal upstaging. In the 10.2% of patients where surgery was performed ≤15 days of diagnosis, 13.9% of DCIS, 11.5% of cT1, and 4.5% of cT2 tumors were upstaged (p &lt; 0.0001). For every 30 days of delay between diagnosis and surgery, the ORs for tumor upstaging, adjusted for covariates, were 1.09 for DCIS (95%CI 1.07-1.10, p&lt; 0.0001), 1.12 for cT1 (95%CI 1.10-1.14, p&lt; 0.0001), and 1.16 for cT2 tumors (95%CI 1.14-1.19, p&lt; 0.0001). For invasive tumors, the adjusted 30-d ORs for upstaging in HR+, HER2+, and TN primaries were 1.12 (95%CI 1.11-1.14), 1.11 (95%CI 1.07-1.15), and 1.19 (95%CI 1.15-1.23), respectively (individual p’s &lt; 0.0001). In the 9.8% of clinically N0 (cN0) patients with a diagnosis-to-surgery interval of ≤15 days, 14.2% were upstaged to node-positive. cN0 patients had an adjusted OR for upstaging to node-positive of 1.06 (95%CI 1.05-1.07, p&lt; 0.0001) for every 30 days of delay. The number of 30-d intervals for cT1mi, cT1a, cT1b, cT1c and cT2 invasive primary tumors to grow 1 mm was 7.8, 7.1, 3.9, 2.8, and 2.0, respectively.
Conclusions:
Even when accounting for clinical stage inaccuracy, longer delays are associated with a quantifiable increase in upstaging and likelihood of becoming node-positive at surgery. This may explain the higher disease-specific and overall mortality associated with preoperative delay found in prior studies. With larger tumors having a higher delay-associated likelihood of upstaging and faster growth rates, delays become more problematic as tumor size increases. This information reinforces the need to minimize preoperative delays by demonstrating their consequences. It also provides data to address some of breast cancer patients’ most pressing preoperative concerns about how fast breast tumors grow and their upstaging potentials while they await treatment.
Citation Format: Richard Bleicher, Karen Ruth, Austin Williams, Eric Ross, Andrea Porpiglia, Allison Aggon, Mary Pronovost, Dennis Holmes. Stage Advancement and The Rate of Growth Associated with Preoperative Delay in Patients Having Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS18-01.