Prolonged Time to Adjuvant Chemotherapy Initiation Was Associated with Worse Disease Outcome in Triple Negative Breast Cancer Patients

Abstract

The optimal time to adjuvant chemotherapy (TTC) for breast cancer (BC) patients remains uncertain. Herein, we aim to evaluate the association between TTC and prognosis among different subtypes in modern era of adjuvant chemotherapy. BC patients receiving operation and adjuvant chemotherapy between January 2009 and December 2015 were included. Enrolled patients were categorized into TTC ≤4 weeks and >4 weeks groups. Relapse-free survival (RFS) and overall survival (OS) were compared according to TTC and analyzed among different BC molecular subtypes. A total of 2611 patients were included. Elder age (P = 0.005), more comorbidities (P <0.001), breast-conserving surgery (P = 0.001), non-invasive ductal carcinoma (P = 0.012), and HER2-positivity (P <0.001) were associated with prolonged TTC. Among whole BC population, no significant difference was observed between two TTC groups in terms of RFS (P = 0.225) or OS (P = 0.355). However, for triple negative (TNBC) patients, TTC >4 weeks was independently related with worse RFS (5-year RFS 81.9% vs 89.3%; HR, 1.89; 95% CI, 1.09 to 3.27; P = 0.024) and OS (5-year OS 84.0% vs 94.0%; HR, 2.49; 95% CI, 1.30 to 4.76; P = 0.006) compared with those TTC ≤4 weeks. Prolonged TTC >4 weeks after BC surgery was not associated with worse survival outcomes in the whole BC patients. However, TTC >4 weeks may increase risk of relapse or death in TNBC patients, which deserves further clinical evaluation.

Figure 1

Distribution of TTC in the study population. The histogram bars refer to number of patients, as indicated by left y-axis. The orange dashed line indicates cumulative percentage of patients who received chemotherapy, as indicated by right y-axis. Abbreviations: TTC, time to adjuvant chemotherapy.

Figure 2

RFS and OS according to TTC in the whole population and in TNBC patients. Kaplan-Meier curves of RFS and OS according to TTC groups in the whole population (A, B) and in TNBC patients (C, D). Abbreviations: RFS, relapse-free survival; OS, overall survival; TTC, time to adjuvant chemotherapy; TNBC, triple negative breast cancer; HER2, human epidermal growth factor receptor 2; No., number.

Figure 3

Interaction between TTC and patient clinicopathological characteristics on RFS. Abbreviations: TTC, time to adjuvant chemotherapy; HR, hazard ratio; RFS, relapse-free survival; CI, confidence interval; N/A, not available; BCS, breast-conserving surgery; IDC, invasive ductal carcinoma; LVI, lymphovascular invasion; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer; OS, overall survival.

Figure 4

Interaction between TTC and patient clinicopathological characteristics on OS. Abbreviations: TTC, time to adjuvant chemotherapy; HR, hazard ratio; RFS, relapse-free survival; CI, confidence interval; N/A, not available; BCS, breast-conserving surgery; IDC, invasive ductal carcinoma; LVI, lymphovascular invasion; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer; OS, overall survival.