Breast Cancer Upstaging Risk and In Vivo Tumor Growth Rates Associated with Preoperative Delays

Preoperative delay when treating breast cancer confers poorer outcomes, but growth rates and the upstaging likelihoods per delay interval remain unknown. This study evaluated upstaging risk, nodal spread, and tumor growth rates in vivo while awaiting treatment.

Registry-based data from the national cancer database was reviewed for patients treated between 2010 and 2020 at commission on cancer-accredited facilities, with nonmetastatic, noninflammatory breast cancer, undergoing surgery first.

Among 1,018,219 patients, 11.5% had primary tumoral upstaging and 14.1% had nodal upstaging. For every 30 d between diagnosis and surgery, the adjusted odds ratios (ORs) for tumor upstaging was 1.11 for ductal carcinoma in situ (DCIS) (95% CI 1.09-1.13, P < 0.0001), 1.13 for cT1 (95% CI 1.11-1.15, P < 0.0001), and 1.18 for cT2 tumors (95% CI 1.15-1.21, P < 0.0001). For invasive tumors, the adjusted 30-d ORs for upstaging in triple negative (TN) primaries were higher (P < 0.0001) at 1.21 (95% CI 1.17-1.25) than hormone receptor-positive (HR+, 1.13; 95% CI 1.12-1.15) and human epidermal growth factor 2-positive (HER2+, 1.09; 95% CI 1.04-1.13). cN0 patients had an adjusted OR for upstaging to node-positive of 1.07 (95% CI 1.06-1.08, P < 0.0001). The number of 30-d intervals for cT1a, cT1b, cT1c, and cT2 tumors to grow 1 mm was 3.95, 2.63, 2.27, and 1.92, respectively, with tumor growth faster in TN tumors (1.29) than HER2+ (4.95) or HR+ (2.35) (P < 0.0001).

Longer delays risk greater upstaging and nodal spread, explaining the association with higher disease-specific and overall mortality in prior studies. Larger and TN tumors have larger delay-associated upstaging likelihoods and in vivo growth rates, making preoperative delays more impactful in these groups.