Clinical Impact of Delaying Initiation of Radiotherapy after Definitive Surgery or Adjuvant Chemotherapy in Breast Cancer Patients

Abstract

For breast cancer (BC) patients with modern therapeutic strategy, whether the time to initiation of adjuvant radiotherapy (TTR) after definitive surgery or last dose of adjuvant chemotherapy (CT) impact on prognosis remains unclear. Current study aims to evaluate the impact of TTR on clinical outcomes. BC pts with stage 0 to III receiving adjuvant radiotherapy (RT) and no neoadjuvant therapy between 2009 and 2015 at our institution were retrospectively reviewed. Pts with no CT were categorized into TTR after definitive surgery ≤10 and >10 wks. Pts with CT were categorized into TTR after last dose of CT ≤12 and >12 wks, and into TTR after definitive surgery ≤180 and >180 days. Clinical outcomes were estimated and compared according to different TTR groups and by molecular subtypes. In total, 1302 pts were enrolled. The number of pts with stage 0, stage I, stage II, and stage III disease were 65, 445, 476, and 309, respectively. The median follow-up was 46 months. Among 981 pts receiving CT, the 5-year recurrence free survival (RFS), locoregional RFS (LRRFS), distant RFS (DRFS) and overall survival (OS) were 88.3%, 96.9%, 89.6% and 93.5%, respectively. In whole 981 pts, initiation of RT >12 wks after last dose of CT was associated with worse OS (5-year 94.4% vs 85.1%, p=0.006), >180 days after definitive surgery was associated with worse RFS (5-y 91.2% vs 85.4%, p=0.003) and DRFS (5-y 97.7% vs 95.1%, p=0.046). TTR >12 weeks after last dose of CT was significantly associated with worse OS in pts with HR+/HER2- tumors (5-y 95.4% vs 85.9%, p=0.01), and with adverse RFS (5-y 84.9% vs 77.1%, p=0.049), DRFS (5-y 87.2% vs 77.1%, p=0.017) and OS (5-y 92.8% vs 77.4%, p=0.001) in pts with stage II to III disease. Initiation of RT >180 days after definitive surgery was associated with decreased RFS (5-y 90.7% vs. 82.8%, p=0.003), DRFS (5-y 91.8% vs. 83.8%, p=0.004) and OS (5-y96.6% vs 91.8%, p=0.026) in pts with HR+/HER2- tumors, and with worse RFS (5-y 89% vs 83%, p=0.027) and DRFS (5-y 90.2% vs 85%, p=0.041) in those with stage II to III disease. In pts with stage I disease, HER2+ tumors or triple negative tumors, however, no correlation between TTR and clinical outcomes was found. In313 pts with no CT, the 5-year LRRFS, RFS, DRFS and OS were 94.8%, 93.5%, 98.3% and 96.1%, no significant difference was found between TTR ≤10 and >10 wks after definitive surgery. While in 26 pts with HER2+ tumors, including 13 ductal carcinoma in situ (DCIS), 12 stage I and one stage II diseases, initiation of RT >10 wks after definitive surgery was associated with decreased RFS (5-y 85.9% vs. 38.1%, p=0.007). In BC pts indicated for CT, prolonged interval between initiation of RT and definitive surgery or after last dose of CT both adversely impact on clinical outcomes, especially in pts with stage II to III disease and those with HR+/HER2- tumors. In pts with DCIS and early invasive BC not indicated for CT, delaying RT after definitive surgery does not significantly impact on prognosis, except for those with HER2+ tumors.