Researchers have identified a gene pattern that may help predict which patients with breast cancer will have early or late disease recurrence following radiation therapy. The ability to predict the timing of recurrence could change—and improve—treatment strategies and determine the length of follow-up needed. These findings were presented by Speers et al at ASCO Breakthrough: A Global Summit for Oncology Innovators (Abstract 112).
Previously, researchers had identified a gene signature linked with response to radiation therapy among patients with breast cancer. They expanded on these results using data from two cohorts of patients who had undergone radiation therapy and breast-conserving surgery. One set of patients (n = 119) was studied to develop a model correlating timing of recurrence with gene expression, and another group (n = 112) was assessed to validate the model. The resulting signature included 41 genes.
“Historically, women who have breast cancer that comes back within the first 3 years have significantly worse outcomes, including much higher rates of death from breast cancer. If we can identify these patients before they develop early, aggressive recurrences, we may be able to more effectively treat these patients.”— Corey Speers, MD, PhD
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Results
In training, the correlation of score to recurrence time was 0.85 (P < 1.3 × 10–31; area under the curve [AUC] = 0.91). External validation in an independent breast cancer validation set accurately identified patients with early vs late recurrences (correlation = 0.75, P = .001, AUC = 0.92) with a sensitivity of 75% and specificity of 100%.
Unique associations of breast cancer intrinsic subtype to timing of local recurrence were found. In univariate and multivariate analyses, the signature remained the most significant factor associated with recurrence. Gene set enrichment analysis of the 41 genes retained within the signature identified proliferation and EGFR concepts associated with early recurrences and luminal and estrogen receptor–signaling pathways associated with late recurrences. Knockdown of genes associated with the early and late recurrences demonstrated novel effects on proliferation and clonogenic survival, respectively.
Corey Speers, MD, PhD
“Historically, women who have breast cancer that comes back within the first 3 years have significantly worse outcomes, including much higher rates of death from breast cancer. If we can identify these patients before they develop early, aggressive recurrences, we may be able to more effectively treat these patients,” said lead author Corey Speers, MD, PhD, Assistant Professor of Radiation Oncology at the University of Michigan. “This work, while exciting and novel, is still premature and not yet ready for clinical adoption. Validation studies in prospective clinical trials are still needed.” ■
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
