RSClin: A new tool for ‘TAILOR-ing’ treatment in early breast cancer

RSClin results and external validation

Among all patients in the meta-analysis cohort, RSClin provided a significantly more accurate prediction of distant recurrence events, in comparison with RS alone or clinical-pathologic factors alone.

External validation was performed using data from real-world outcomes from the 1,098 evaluable node-negative patients in the Clalit Health Services registry, of whom 876 received endocrine therapy alone and 222 received endocrine therapy plus chemotherapy.

RSClin estimates of distant recurrence closely approximated the observed risk in the registry (standardized hazard ratio, 1.73; 95% confidence interval, 1.40-2.15; P < .001). Within each RSClin risk quintile, the average 10-year risk estimate approached the observed Kaplan-Meier estimates in the cohort (Lin concordance correlation = 0.962).
 

Shared decision-making

For many years, the dilemma of whether to recommend adjuvant chemotherapy to a patient with early breast cancer has prompted the generation of tools to quantify a patient’s risk of recurrence and the magnitude of benefit for endocrine therapy and/or chemotherapy.

When the original Adjuvant! Online program was developed, genomic risk profiling was in its infancy. Genomic tools such as the 21-gene RS have subsequently demonstrated that they can help optimize the adjuvant treatment we recommend.

The RSClin tool provides more precise, individualized information than does clinical-pathological or genomic data alone. It prognosticates the risk of distant recurrence of breast cancer, which patients and providers fervently wish to minimize.

RSClin estimates the incremental benefit of contemporary adjuvant chemotherapy over modern endocrine therapy alone, in absolute values, for individual patients. This transparent, discrete, easily explained information is vital for counseling patients.

However, as highlighted in an editorial published in the Journal of Clinical Oncology, RSClin is not without its potential drawbacks. These include:

• Tumor heterogeneity leading to misleading results.
• Variable patient adherence to endocrine therapy or chemotherapy.
• The influence of comorbid conditions on the risk/benefit ratio.
• The potential of ovarian function suppression in young women to approach the magnitude of benefit associated with chemotherapy.

Accordingly, RSClin may be the latest and best available tool, but it will not be the last.

For patients with RS above 26, for older women with intermediate RS, and for younger women with a low RS and low clinical-pathologic features, RSClin may not influence treatment recommendations.

However, for the common scenario of an intermediate-risk RS and a mix of pathologic features, the accurate prognostication for distant recurrence risk and estimate of absolute benefit from chemotherapy will be terrifically helpful to oncology caregivers.

Dr. Sparano disclosed funding from the National Cancer Institute and travel support from Rhenium.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.