BackgroundThe National Comprehensive Cancer Network suggested that older women with low‐risk breast cancer (LRBC; i.e., early‐stage, node‐negative, and estrogen receptor‐positive) could omit adjuvant radiation treatment (RT) after breast‐conserving surgery (BCS) if they were treated with hormone therapy. However, the association between RT omission and breast cancer‐specific mortality among older women with comorbidity is not fully known.Methods1105 older women (≥65 years) with LRBC in 1998–2012 were queried from the Surveillance, Epidemiology, and End Results–Medicare Health Outcomes Survey data resource and were followed up through July 2018. Latent class analysis was performed to identify comorbidity burden classes. A propensity score‐based inverse probability of treatment weighting (IPTW) was applied to Cox regression models to obtain subdistribution hazard ratios (HRs) and 95% CI for cancer‐specific mortality considering other causes of death as competing risks, overall and separately by comorbidity burden class.ResultsThree comorbidity burden (low, moderate, and high) groups were identified. A total of 318 deaths (47 cancer‐related) occurred. The IPTW‐adjusted Cox regression analysis showed that RT omission was not associated with short‐term, 5‐ and 10‐year cancer‐specific death (p = 0.202 and p = 0.536, respectively), regardless of comorbidity burden. However, RT omission could increase the risk of long‐term cancer‐specific death in women with low comorbidity burden (HR = 1.98, 95% CI = 1.17, 3.33), which warrants further study.ConclusionsOmission of RT after BCS is not associated with an increased risk of cancer‐specific death and is deemed a reasonable treatment option for older women with moderate to high comorbidity burden.