br This study is a large population based study
This study is a large, population-based study to evaluate RS use, categorize RS distribution and evaluate factors associated with high-risk scores and survival in the older women with breast cancer. However, there are inherent limitations which must be considered. As a retrospective study, it is subject to selection bias as providers are utilizing clinical factors to determine which patients are most likely to benefit from RS testing. This may be especially true in the older Angeli’s Salt as the benefits of chemotherapy (even among high-risk patients) must be weighed against the risks, especially for certain subtypes such as invasive lobular carcinoma . If a pa-tient is too frail to undergo chemotherapy, RS testing is unnecessary
as it would not alter clinical management. This bias may contribute to our finding of why the year of diagnosis correlates with lower likelihood of a high-risk RS, as, over time, preferential selection of RS testing is likely to increase. Secondly, while the SEER database provides a large repository of clinical information, comorbid illness and functional status is not recorded. Patient frailty and comorbidi-ties likely influence the decision to obtain a RS test and would cer-tainly contribute to adjuvant treatment decisions and overall survival. Additionally, HER2 status was not available throughout the entire study period, and HER2 status is an important clinical in-dicator for RS testing. Finally, we were unable to determine use of endocrine therapy and completion of adjuvant chemotherapy from the SEER database, and this information would allow a deeper un-derstanding of why chemotherapy may not portend a survival ad-vantage in older patients.
Despite these limitations, this study utilized a large population-based dataset to determine RS distribution and factors associated with RS testing. We also determined factors associated with an increased likelihood of high-risk RS categorization, and survival in older women with ER-positive breast cancer. This study provides further understand-ing of prognostic and treatment trends in this distinct subgroup of pa-tients with breast cancer. Future work on the utility of RS testing in the older population with breast cancer and the use of adjuvant chemo-therapy is necessary to provide more evidence-based management strategies for these patients.
Conflict of Interest
TMT declares that he holds a position on the advisor board of Genomic Health Inc. The authors declare no other conflicts of interest.
SK: Assisted in study conception, study design, data interpretation, and manuscript preparation.
AMA: Assisted in study conception, study design, data interpretation, and manuscript preparation.
SM: Assisted in study conception, data collection, data analysis and in-terpretation, and critical revision of manuscript.
JWD: Assisted in data analysis and critical revision of the manuscript.
EHJ: Assisted in data analysis and critical revision of the manuscript.
TMT: Assisted in study conception, study design, data interpretation, manuscript preparation, and final approval of the manuscript. JYCH: Assisted in study conception, study design, data interpretation, manuscript preparation, and final approval of the manuscript.
 Fisher B, Dignam J, Wolmark N, et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst 1997;89: 1673–82.
 Houterman S, Janssen-Heijnen MLG, Verheij CDGW, et al. Comorbidity has negligible impact on treatment and complications but influences survival in breast cancer pa-tients [Internet]. Br J Cancer 2004;90:2332–7 Available from http://www.ncbi.nlm. nih.gov/pmc/articles/PMC2409529/.  Chen H, Zhou M, Tian W, et al. Effect of age on breast cancer patient prognoses: a population-based study using the SEER 18 database [Internet]. PLoS One 2016;11: e0165409 Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087840/.