Effects of Radiation Therapy and Comorbidity on Health-Related Quality of Life and Mortality Among Older Women With Low-Risk Breast Cancer: Protocol for a Retrospective Cohort Study
Authors: Lee Eunkyung , Hines Robert B , Wright Jean L , Nam Eunji , Rovito Michael J , Liu Xinliang 
Published: October 2020

Background
The National Comprehensive Cancer Network Breast Cancer Guidelines Committee suggests that the omission of adjuvant radiation therapy (RT) after breast-conserving surgery can be a reasonable option among older women with low-risk breast cancer (early-stage, estrogen receptor-positive, and node-negative) if they are treated with endocrine therapy. However, RT usage in this group of women still exceeds 50%. Conversely, older women tend to forego RT (even when necessary) due to cost, inconvenience, and potential adverse responses associated with RT. Understanding health-related quality of life (HRQOL) change with receipt of RT among older women in the modern era is limited due to the under-representation of this population in clinical trials.

Objective
The proposed study aims to examine the associations of RT with HRQOL trajectories as well as survival outcomes among older women with 5-10 years of follow-up. We will also assess whether prediagnosis comorbidity burden influences receipt of RT and whether the associations between RT and HRQOL trajectory and survival outcomes are modified by the comorbidity burden.

Methods
We will use a retrospective cohort study design with the population-based Surveillance, Epidemiology, and End-Results database linked to the Medicare Health Outcomes Survey (SEER-MHOS). Older women (≥65 years) who were diagnosed with low-risk breast cancer in 1998-2014, received breast-conserving surgery, and participated in MHOS 1998-2016 are eligible for this analysis. The latent class analysis clustering method will be used to identify each patient’s prediagnosis comorbidity burden, and HRQOL will be evaluated using the Short Form 36/Veterans RAND 12-Item Health Survey scales. The inverse-weighted estimates of the probability of treatment will be included to control for treatment selection bias and confounding effects in subsequent analysis. The association of RT with HRQOL trajectory will be evaluated using inverse-weighted multilevel growth mixture models. The inverse-weighted Cox regression model will be used to obtain hazard ratios with 95% CIs for the association of RT with survival outcomes. Differential effects of RT on both outcomes according to comorbidity burden class will also be evaluated.

Results
As of October 2020, the study was approved by the institutional review board, and SEER-MHOS data were obtained from the National Cancer Institute. Women with low-risk breast cancer who met inclusion and exclusion criteria have been identified, and prediagnosis comorbidity burden class has been characterized using latent class analysis. Further data analysis will begin in November 2020, and the first manuscript will be submitted in a peer-reviewed journal in February 2021.

Conclusions
This research can potentially improve clinical outcomes of older women with low-risk breast cancer by providing them additional information on the HRQOL trajectories when they make RT treatment decisions. It will facilitate informed, shared treatment decision making and cancer care planning to ultimately improve the HRQOL of older women with breast cancer.

International Registered Report Identifier (IRRID)
DERR1-10.2196/18056