Surgical Delay-Associated Mortality Risk Varies by Subtype in Loco-Regional Breast Cancer Patients in SEER-Medicare

Abstract

Substantial evidence supports that delay of surgery after breast cancer diagnosis is associated with increased mortality risk, leading to the introduction of a new Commission on Cancer quality measure for receipt of surgery within 60 days of diagnosis for non-neoadjuvant patients. Breast cancer subtype is a critical prognostic factor and determines treatment options; however, it remains unknown whether surgical delay-associated breast cancer-specific mortality (BCSM) risk differs by subtype. This retrospective cohort study aimed to assess whether the impact of delayed surgery on survival varies by subtype (hormone [HR]+/HER2-, HR-/HER2-, and HER2+) in patients with loco-regional breast cancer who received surgery as their first treatment between 2010-2017 using the SEER-Medicare. Continuous time to surgery from diagnostic biopsy (TTS; days) in reference to TTS = 30 days. BCSM were evaluated as flexibly dependent on continuous time (days) to surgery from diagnosis (TTS) using Cox proportional hazards and Fine and Gray competing-risk regression models, respectively, by HR status. Inverse propensity score-weighting was used to adjust for demographic, clinical, and treatment variables impacting TTS. Adjusted BCSM risk grew with increasing TTS across all subtypes, however, the pattern and extent of the association varied. HR+/HER2- patients exhibited the most pronounced increase in BCSM risk associated with TTS, with approximately exponential growth after 42 days, with adjusted subdistribution hazard ratios (sHR) of 1.21 (95% CI: 1.06-1.37) at TTS = 60 days, 1.79 (95% CI: 1.40-2.29) at TTS = 90 days, and 2.83 (95% CI: 1.76-4.55) at TTS = 120 days. In contrast, both HER2 + and HR-/HER2- patients showed slower, approximately linear growth in sHR, although non-significant in HR-HER2-.

Keywords: Breast cancer-specific mortality; HER2; Hormone-receptor; SEER-Medicare; Surgical delay; Tumor subtype.

Figure 1

SEER-Medicare Exclusion Scheme

Figure 2

Adjusted risk (subdistribution hazard ratio [sHR]) of breast cancer-specific mortality (BCSM) associated with continuous TTS in HR+/HER2−, HER2+, and HR−/HER2− locoregional breast cancer patients in a SEER-Medicare cohort.

Figure 3

Adjusted cumulative incidence function (CIF) of breast cancer-specific mortality (BCSM) in HR+/HER2−, HER2+, and HR−/HER2− locoregional breast cancer patients at specified TTS points (30, 60, 90, and 120 days) in a SEER-Medicare cohort.