Delayed initiation of radiation therapy is associated with inferior outcomes for breast cancer patients with hormone receptor-negative tumors after breast-conserving surgery

Xiaoyan Ma; Jie Chen; Ding Ma; Yizhou Jiang; Zhebin Liu; Sheng Chen; Ying Zhang; Yizhou Shen; Xiaoli Yu; Zhaozhi Yang; Shuang Li; Miao Mo; Yongxiang Qian; Guangyu Liu; Jiong Wu; Zhiming Shao; Keda Yu; Genhong Di

doi:10.21037/gs-20-717

Delayed initiation of radiation therapy is associated with inferior outcomes for breast cancer patients with hormone receptor-negative tumors after breast-conserving surgery

Gland Surg. 2021 Sep;10(9):2631-2643. doi: 10.21037/gs-20-717.

Authors

Xiaoyan Ma^{1

2}, Jie Chen³, Ding Ma^{1

2}, Yizhou Jiang^{1

2}, Zhebin Liu^{1

2}, Sheng Chen^{1

2}, Ying Zhang^{1

2}, Yizhou Shen^{1

2}, Xiaoli Yu^{2

4}, Zhaozhi Yang^{2

4}, Shuang Li⁵, Miao Mo^{2

6}, Yongxiang Qian³, Guangyu Liu^{1

2}, Jiong Wu^{1

2}, Zhiming Shao^{1

2}, Keda Yu^{1

2}, Genhong Di^{1

2}

Affiliations

¹ Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Thyroid and Breast Surgery, First People's Hospital of Taicang, Taicang, China.
⁴ Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁵ Department of Breast Surgery, Liaoning Province Cancer Hospital, Shenyang, China.
⁶ Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract

Background: To investigate whether the interval between adjuvant chemotherapy (CT) completion and postoperative radiation therapy initiation (ICR) after breast-conserving surgery (BCS) affects ipsilateral breast tumor recurrence (IBTR) or survival.

Methods: All women who were diagnosed with invasive breast cancer and underwent BCS between 2005 and 2014 were included. In total, 1,472 patients underwent adjuvant CT followed by postoperative radiation therapy (RT) (CT+), whereas 402 patients received postoperative RT alone (CT-). Analyses were stratified by ICR and the interval between surgery and the initiation of postoperative RT (ISR) in these two cohorts. The cutoff points for treatment delay were 47 days in the CT+ cohort and 69 days in the CT- cohort. IBTR, local-regional failure (LRF), disease-free survival (DFS), and overall survival (OS) were assessed through Kaplan-Meier (K-M) analysis. Univariate and multivariate regression analyses were performed to determine the prognostic factors of survival outcomes.

Results: The median follow-up duration was 56 months. There was an association between a delay in ICR and an increase in IBTR in the CT+ group (P=0.014 for intervals ≤47 vs. >47 days). This association was confirmed by multivariate analyses [hazard ratio (HR) of 2.766; P=0.046] in the hormone receptor-negative subgroup. The 5-year cumulative incidence rates of IBTR were 1.3% and 3.3% (≤47 vs. >47 days, respectively) in the CT+ cohort. For patients in the CT- cohort, a longer delay of initiation of postoperative RT (≤69 vs. >69 days) significantly decreased DFS (HR of 6.430; P=0.002). The 5-year cumulative incidence rates of disease recurrence were 3.0% for RT starting ≤69 days after surgery and 12.6% for RT starting >69 days after surgery.

Conclusions: A high IBTR rate was related to an ICR beyond 47 days. Delay of RT after CT or surgery among patients who undergo BCS should be avoided, especially among patients in the hormone receptor-negative subgroup.

Keywords: Breast-conserving surgery (BCS); delay; local recurrence; radiation therapy (RT); surgery-radiotherapy interval.