Impact of Delayed Neoadjuvant Systemic Chemotherapy on Overall Survival Among Patients with Breast Cancer

Background: Delays in the initiation of therapy among patients with early stage breast cancer (BC) can negatively affect outcomes. Patients treated with neoadjuvant systemic chemotherapy (NSC) usually display tumors with high-risk features. Considering these high-risk characteristics and the evidence supporting adverse outcomes associated with delays in adjuvant chemotherapy initiation, we sought to determine whether a delay in NSC initiation is associated with overall survival (OS). Methods: We identified patients diagnosed between January 1995 and December 2015 with invasive primary BC (stage I–III) who received NSC at MD Anderson Cancer Center. Patients were categorized according to their time from BC diagnosis to NSC (in days) into three subgroups: 0-30, 31–60, and ≥61 days. Primary endpoint was OS. Descriptive statistics and Cox's proportional hazard models were used. Results: A total of 5,137 patients were included. Median follow-up was 6.5 years. The 5-year OS estimates according to time to NSC were 87%, 85%, and 83% in patients who received NSC within 0–30, 31–60, and ≥61 days after diagnosis, respectively (p =.006). In multivariable analysis, compared with time to NSC of 0–30 days, delayed NSC ≥61 days was associated with an increased risk of death (31–60 days: hazard ratio [HR] = 1.05 [95% confidence interval (CI) 0.92–1.19]; ≥61 days, HR = 1.28 [95% CI 1.06–1.54]). In stratified analyses, the association between delay in NSC initiation and increased risk of death was statistically significant for patients with stage I and II BC (31–60 days: HR = 1.22 [95% CI 1.02–1.47]; ≥61 days, HR = 1.41 [95% CI 1.07–1.86]) and among patients with HER2-positive tumors (≥61 days, HR = 1.86 [95% CI 1.21–2.86]). Conclusion: A delay in NSC initiation of more than 61 days after BC diagnosis was associated with an increased risk of death. Early initiation of NSC should be a priority; multidisciplinary teams must focus on coordination of care and patient-centered, timely treatment planning and delivery. Implications for Practice: The results of this study showed that a delay in neoadjuvant systemic chemotherapy initiation of more than 61 days after breast cancer diagnosis is associated with an increased risk of death; therefore, efforts must focus on early initiation of therapy, which should be a priority. Multidisciplinary teams must enhance coordination of care and patient-centered, timely treatment planning and delivery.