Nonanatomic factors, such as histologic grade and biomarkers, can guide breast cancer management
but are not included in the current TNM staging system.
To use as an example the triple-negative phenotype (TNP) defined by the absence of estrogen
receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) to examine
whether such inclusion improves the prognostic accuracy of TNM staging for breast cancer.
Design, Setting, and Participants
Women diagnosed with primary invasive ductal breast cancer from January 1, 1991, through December
31, 2008, were identified from a prospective institutional database. Excluded were patients who
received neoadjuvant therapy, those whose staging information was incomplete, or those whose tumor
lacked ER, PR, and HER2 data. Breast cancers were categorized by TNM stage and by the presence or
absence of TNP.
Main Outcomes and Measures
Overall survival at 5 years.
Database review identified 1842 consecutive eligible patients with breast cancer. When patients
were stratified by TNM stage, overall survival curves for those with TNP breast cancer matched those
for patients whose non-TNP breast cancer was 1 TNM stage higher. Multivariable analysis showed that
TNP status was a powerful prognostic variable, and the likelihood ratio test revealed that the
prognostic accuracy of the TNM staging system that incorporated TNP was superior to the current TNM
staging system (P < .001). A TNM staging system that incorporated
TNP reduced early-stage compression by 15%.
Conclusions and Relevance
The internationally recognized and easily reproducible examination of ER, PR, and HER2 status
exemplifies how nonanatomic factors can improve the prognostic accuracy of breast cancer