The most recent version of the National Comprehensive Cancer Network (NCCN) guidelines for the management of invasive breast cancer (version 1.2017) incorporates the use of genomic expression profiling to assist in adjuvant treatment decision-making in women with hormone receptor–positive/HER2-negative breast cancer.
The state of biomarkers and multigene assays was reviewed by Lee S. Schwartzberg, MD, Executive Director of the West Clinic, Memphis, at the NCCN 22nd Annual Conference held in Orlando, FL.
Among the available multigene assays are the 21-gene recurrence score (Oncotype DX), the 70-gene prognostic index (MammaPrint), and the Breast Cancer Index. The 21-gene recurrence score is the most widely used; it incorporates 16 informative cancer genes and 5 reference genes into its assay to produce a risk score. In the NSABP-14 trial, recurrence rates were 6.8% for patients with a low recurrence score (<18), 14.3% for those with an intermediate score (18-30), and 30.6% for those with a score considered to be high (≥31).
“The assays are all prognostic, and in general they are also all predictive of endocrine therapy benefit,” said Dr Schwartzberg. For example, genomic profiling was found to successfully predict the benefit of endocrine therapy in the TAILORx study, he said. In this clinical trial, which enrolled >10,000 patients, those with a low-risk recurrence score (0-10) and who received endocrine therapy alone had a <1% rate of distant recurrence at 5 years, a rate of freedom from recurrence of 98.7%, an invasive disease-free survival rate of 93.8%, and an overall survival of 98.0%.
Genomic profiling can also be used to select for chemotherapy. “Many clinicians feel that genomic profiling for the prediction of chemotherapy benefit may be the most impactful way we can use these tests,” said Dr Schwartzberg.
In the MINDACT study of patients with node-negative breast cancer, those with high clinical risk and low genomic risk per the 70-gene signature who did not receive adjuvant chemotherapy had a rate of distant metastasis-free survival of 94.7% at 5 years, which met the study’s primary end point. Distant metastasis-free survival was 98% among patients with a low clinical risk and low genomic risk, whereas it was 90.6% for those at high risk by both assessments and who received chemotherapy.
Outcomes for the intermediate-risk group of patients in TAILORx who were randomized to chemotherapy or placebo are not yet available; these results should further determine the extent of benefit with chemotherapy.
The 21-gene recurrence score has also been found to be prognostic in women with node-positive cancer, although its predictive value in this group remains uncertain, Dr Schwartzberg noted.
Genomic Profiling for Predicting Late Relapse
The evidence also indicates that genomic classifiers are prognostic for late recurrence, which is common in estrogen receptor–positive patients, he said. The Early Breast Cancer Trialists’ Group found that distant recurrence rates continue to increase after 5 years of tamoxifen exposure. Genomic classifiers may also predict benefit from extended adjuvant therapy.
NCCN Guidance for Incorporating Recurrence Score
Dr Schwartzberg concluded with a summary of how the 21-gene recurrence assay is incorporated into the latest version of the NCCN guideline. The 21-gene recurrence score assay should be considered for use in patients with hormone receptor–positive, HER2-negative, node-negative breast cancer whose tumors are >0.5 cm. For patients with a low recurrence score (<18), adjuvant endocrine therapy alone is recommended. For those with an intermediate recurrence score (18-30), adjuvant endocrine therapy or adjuvant chemotherapy followed by endocrine therapy is acceptable. A high recurrence score (≥31) merits both adjuvant endocrine therapy and chemotherapy.
As footnotes, the NCCN states that the 21-gene recurrence assay can be considered in selected patients with 1 to 3 positive nodes, and that other genomic expression profiling assays are also prognostic but are supported by less evidence to predict response to chemotherapy.
Pan H, Gray RG, Davies C, et al. Predictors of recurrence during years 5-14 in 46,138 women with ER+ breast cancer allocated 5 years only of endocrine therapy (ET). J Clin Oncol. 2016;34(suppl):Abstract 505.