Abstract P4-12-19: Impact of delaying initiation of RT following definitive surgery or following adjuvant chemotherapy on survival outcomes in breast cancer patients

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Abstract Purpose: For breast cancer (BC) patients treated with adjuvant chemotherapy (CT), the optimal time to initiation of adjuvant radiotherapy (TTR) from definitive surgery is still controversial especially with modern systemic therapy, while the impact of TTR from completion of CT has not been reported to date. The current study aims to evaluate the impact of TTR from surgery and from completion of CT on survival outcomes in non-metastatic BC patients according to BC subtype. Methods and Materials: BC patients who were treated with definitive surgery followed by adjuvant CT and received adjuvant radiotherapy (RT) from January 2009 through December 2015 in a single institution were included in this study. Patients receiving neoadjuvant therapy were not enrolled. According to our clinical practice, if adjuvant treatments were well organized, RT could be initiated within 180 days following surgery and with completion of most up-to-date CT regimens. As a result, patients were categorized into two groups according to TTR from surgery as ≤180 and >180 days and according to TTR from CT as ≤12 and >12 weeks. The survival curves were estimated by the Kaplan-Meier method and compared by log-rank test. The independent effect of TTR from surgery and TTR from CT were separately tested using a Cox proportional hazards model for multivariate analysis after adjusting for these variables that were statistically significant on univariate analysis. Results: In total, 989 patients were enrolled. The number of patients with HR-positive, triple-negative (TN) and HER2-positive BC was 590, 196, and 203, respectively. The median follow-up was 43 (range: 4 to 117) months. The median TTR from surgery was 180 (range: 24 to 117) days and from completion of CT was 29 (range: 7 to 247) days. The 5-year recurrence-free survival (RFS), locoregional RFS (LRRFS), distant RFS (DRFS) and overall survival (OS) were 88.0%, 96.9%, 89.3% and 93.5%, respectively. The 5-year OS was 94.7%, 88.3% and 95.2% in patients with HR-positive, TN and HER-2 positive BC, respectively (P<0.01). Initiation of RT >12 weeks after completion of CT was associated with worse OS (5-year 94.0% vs 85.1%, p=0.006), >180 days after surgery was associated with worse DRFS (5-y 91.7% vs 86.9%, p=0.004) and worse RFS (5-y 90.7% vs 85.4%, p=0.003). In the multivariable analysis, TTR after completion of CT remained independent prognostic factor for OS (hazard ratio [HR], 2.81; 95% CI, 1.17 to 6.74; P=0.02) and TTR >180 days after surgery was also significantly associated with worse DRFS (HR, 1.79; 95% CI, 1.09 to 2.93; P=0.02) and RFS (HR, 1.71; 95% CI, 1.09 to 2.69; P=0.02). In patients with HR-positive BC, TTR >12 weeks after completion of CT was significantly associated with worse OS, while >180 days after surgery was with adverse DRFS (5-y 91.0% vs. 83.8%, p=0.004), RFS (5-y 89.8% vs. 82.8%, p=0.003), and OS (5-y96.6% vs 91.8%, p=0.026). However, these associations between TTRs and survival outcomes were not found in patients with HER2-positive BC or TNBC. Conclusion: In BC patients indicated for CT, delaying initiation of RT after definitive surgery or after completion of CT both adversely impact on survival outcomes. Efforts should be made to minimize delays in the initiation of RT in the above two TTR settings. Citation Format: Lu Cao, Jia-Yi Chen. Impact of delaying initiation of RT following definitive surgery or following adjuvant chemotherapy on survival outcomes in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-19.