The online RSClin tool incorporating clinical-pathological data and the results of a 21-gene recurrence score (RS) was able to estimate the risk of distant recurrence (DR) and the benefit from adjuvant chemotherapy in specific patients with early breast cancer. The development and validation of this tool were outlined in an article appearing on 11 December 2020 in the Journal of Clinical Oncology.

In this article, lead author Joseph A. Sparano of the Montefiore Medical Centre and the Albert Einstein College of Medicine and New York, USA and colleagues emphasised that the 21-gene RS is prognostic for DR and predictive for chemotherapy benefit in early breast cancer, while clinical-pathological factors are only prognostic. However, the RSClin tool integrates genomic and clinical features, thereby offering the potential to guide the use of adjuvant chemotherapy with greater precision.

Professor Sparano and co-investigators developed the new RSClin tool that integrates the RS with the patient’s age as well as tumour grade and size using a patient-specific meta-analysis that included data from 10,004 women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and node-negative breast cancer. Of these women, endocrine therapy was administered to 577 patients in the randomised B-14 and 4,854 in the TAILORx trials; an additional 4,573 women also received endocrine therapy plus chemotherapy in TAILORx.

The investigators used Cox models to compare results for the RSClin with the RS and clinical pathological features separately using likelihood ratio tests. In addition, RSClin estimates of DR used a baseline risk employing TAILORx event rates to reflect current medical practice and a patient-specific estimator of absolute chemotherapy benefit was computed using individualised relative chemotherapy effect from the TAILORx and B-20 trials.

In order to perform an external validation of risk estimation, RSClin estimated risk was compared with the observed risk from data of 1,098 women contained in the Clalit registry.

The RSClin tool provides information for DR risk and chemotherapy benefit that may be useful in guiding the use of adjuvant chemotherapy

This analysis found that the RSClin provide prognostic information for DR that was additional to that provided by either the RS or clinical-pathological factors alone (both p = 0.001, likelihood ratio test).

External validation demonstrated that the RSClin risk estimate was prognostic for DR risk in the real world data contained in the Clalit registry, hazard ratio (HR) 1.73 (95% confidence interval [CI] 1.40-2.15; p = 0.001). Furthermore, the estimated risk provided a close approximation of the observed 10-year risk (Lin concordance 0.962).

An example of potential clinical use was provided using the new prediction tool in a 55-year-old woman with a clinical low-risk 1.5-cm intermediate-grade tumour. With the RSClin, the absolute chemotherapy benefit estimate ranged from 0% to 15% as the RS ranged from 11 to 50.


The RSClin tool integrates genomic and clinical features to determine risk that may guide the decision for adjuvant chemotherapy in node-negative breast cancer and provides more individualised information than clinical-pathological or the RS alone.

According to the authors, they have developed the RSClin, a new prognostic tool, that reflects current medical practice for HR-positive, HER2-negative, and node-negative breast cancer that was externally validated regarding the precision of the tool in providing prognostic estimates for 10-year DR rate in an independent real-world cohort.

They further wrote that the RSClin tool has been enhanced and now provides individualised estimates of absolute chemotherapy benefit. The investigators demonstrated that the effect prediction provided by the RS result, based on contemporary treatments, contributes substantially to the estimate of absolute chemotherapy benefit.

They advise that, as demonstrated by this report, PSMA methods may be used in conjunction with randomised clinical trials to develop tools to facilitate more effective application of precision medicine in cancer therapy.

This study was supported by the US National Cancer Institute. Additional support was provided by the Breast Cancer Research Foundation, the Komen Foundation, and the Breast Cancer Research Stamp (BCRS) issued by the United States Postal Service.


Sparano JA, Crager MR, Tang G, et al. Development and Validation of a Tool Integrating the 21-Gene Recurrence Score and Clinical-Pathological Features to Individualize Prognosis and Prediction of Chemotherapy Benefit in Early Breast Cancer. Journal of Clinical Oncology; 11 December 2020. DOI: https://doi. org/10.1200/JCO.20.03007.