Mark Pegram, MD, Reviews Utility of Breast Cancer Index in Early-Stage HR+ Breast Cancer

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with Mark Pegram, MD, Suzy Yuan-Huey Hung Endowed Professor of Medical Oncology at Stanford University School of Medicine, about an analysis of results from the IDEAL trial comparing the predictive performance of the Breast Cancer Index (BCI) score, based on the HOXB13/IL17RB (H/I) ratio, and Clinical Treatment Score Post-5 years (CTS5). This trial aimed to determine if either measure could determine which patients would benefit from 5 years of extended treatment with endocrine therapy vs 2.5 years.

Transcript:

We know that, from a number of studies, that 10 years of endocrine therapy is superior to 5 [years], but not in everyone. To have a diagnostic biomarker to help make that decision, which is a very difficult decision, to select between long, extended adjuvant endocrine therapy vs standard 5-year adjuvant endocrine therapy would be most helpful. To that end, the breast cancer index is a 2-gene ratio of the HOXB13 gene expression divided by the IL17RB gene expression. In contrast to other biomarkers and clinical pathologic variables in early-stage breast cancer that are prognostic, this gene ratio is predictive of a favorable response to extended adjuvant endocrine therapy for up to 10 years, so it’s not merely a prognostic factor.

On the other hand, we have other clinical tools like the clinical treatment score post 5-years, which is a clinical algorithm incorporating clinical and pathologic variables, called CTS5, that [includes] lymph node status, age, tumor size, and tumor grade. That’s been shown to be prognostic for distant recurrence. At this ASCO, the IDEAL investigators applied both of those biomarkers to the IDEAL trial, an investigation on the duration of extended letrozole. The IDEAL trial was a randomized study in patients who had had either tamoxifen, aromatase inhibition, or tamoxifen followed by aromatase inhibition for the first 5 years of adjuvant endocrine therapy, whereupon they were then randomized to receive either 2.5 or 5 or more years of extended adjuvant letrozole therapy. The BCI was measured for patients enrolled in that study. We now have the CTS5 clinical prognostic information on this database as well. The IDEAL investigators reported Kaplan-Meier estimates and did Cox regression models to look for the interaction P-value between long-term outcomes for either short or extended adjuvant letrozole therapy, and either the clinical CTS5 score or the BCI H/I ratio. This analysis had 818 patients with hormone receptor–positive disease, so a sizable well controlled study. About two-thirds of the patients were over 50 years old at the time of their surgery. About half the patients had T2 tumors [48%], about half had grade 2 tumors [47%], and 73% were lymph node positive that were included in this analysis. The BCI result was high and about half the patients scored as low. Then we applied this algorithm for the CTS5.

Reference

Liefers G-J, Noordhoek I, Putter H, et al. Predictive performance of breast cancer index (BCI) and clinical treatment score post-5 years (CTS5) in the IDEAL study. J Clin Oncol. 2022;40(suppl 16):545. Doi: 10.1200/JCO.2022.40.16_suppl.545