Oncotype-DX, an assay used by women with hormone positive (HP+), HER2-negative, lymph node negative (LNN) early breast cancer (EBC) to predict risk of BC recurrence, is recommended by the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and for staging by the American Joint Commission on Cancer.
The TAILORx trial, a prospective clinical study conducted in over 10,000 women with HR+, HER2-, LNN EBC who met established guidelines for the use of adjuvant chemotherapy, showed that Oncotype-DX was able to identify women at very low risk of recurrence (recurrence scores of 0-10) following 5 years of endocrine monotherapy. Initial results of the TAILORx trial were published in 2015 in the New England Journal of Medicine, but they were not able to provide recommendations on the use of adjuvant chemotherapy for women with intermediate-risk (recurrence scores of 11-25) Oncotype-Dx scores.
It was not until June 2018 that the results of patients with intermediate-risk Oncotype-DX recurrence scores were published and showed that women with recurrence scores of 11 to 25 can safely forego adjuvant chemotherapy, although some benefit was found for women <50 years with a recurrence score of 16 to 25. Another important outcome of this latter publication was the consolidation of grouping of scores into low-risk (0-25) and high-risk (26-100) of recurrence, thereby eliminating the intermediate-risk category, as this group became part of the low-risk recurrence group.
Despite the availability of Oncotype-DX, two-thirds of eligible women do not undergo the prognosticative testing. One factor for this underutilization may be related to the cost of the test (approximately $4,000), which may put it out of reach for many low-income or economically disadvantaged women. To help address this concern, a user-friendly nomogram utilizing clinicopathologic characteristics of Oncotype-DX tested patients was developed to serve as a surrogate prediction model for Oncotype-DX scores. However, the first version of this nomogram was released prior to the publication of the final TAILORx results in 2018.
The original investigators updated the nomogram to reflect the latest clinical findings and to test the predictive value of clinicopathologic variables in forecasting BC recurrence risk using the new TAILORx binary (low-risk, high-risk) stratification. Clinicopathologic variables that were incorporated into the nomogram for their prognostic and/or predictive value included age, tumor size, tumor grade, progesterone receptor status, and the histologic type of BC. The updated nomogram included data from 84,339 Oncotype-DX tested HR+, HER2-, LNN women with tumors measuring 6 mm to 50 mm.
The revised nomogram’s overall accuracy was 86.8% with a sensitivity of 99.2%, specificity of 18.6%, positive predictive value of 87%, and negative predictive value of 80.2% for low-risk Oncotype-DX scores and a sensitivity of 18.6%, specificity of 99.2%, positive predictive value of 80.2%, and negative predictive value of 87% for high-risk recurrence scores. This revised and validated nomogram is freely accessible through the University of Tennessee Medical Center’s website.
In the updated nomogram, tumor grade and progesterone receptor status were the highest significant predictors for both low-risk and high-risk patients, followed by histologic tumor type, tumor size, and age. Furthermore, results of high-risk recurrence scores were applicable to women of all ages, but the low-risk scores were most predictive in women older than age 50 years.
Pharmacists can utilized this online nomogram to determine the best course of therapy for their HP+, HER2-negative, LNN EBC patients.
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