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 and 2017 using the SEER-Medicare database. Exposure of this study was 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 Fine and Gray competing-risk regression models, respectively, by HR status. Inverse propensity score-weighting was adjusted 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.

Fig. 1

Cohort exclusion scheme

Fig. 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

Fig. 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