An Eighteen-Gene Classifier Predicts Locoregional Recurrence in Post-Mastectomy Breast Cancer Patients

• No molecular markers are available to determine post-mastectomy radiotherapy for breast cancer patients.
• Statistically about 2-8% N0 and 20% of N1 mastectomy patients would develop local/regional recurrence (LRR).
• An 18-gene classifier is capable of identifying patients at risk for LRR after mastectomy.There is no consensus whether to give post-mastectomy radiotherapy to all N1 patients according to the St. Gallen consensus meeting in 2015. Currently about one half of N1 mastectomy patients have been given adjuvant radiotherapy in the United States. From a separate patient population, we now have developed an 18-gene classifier included in our previously published 34-gene panel. This diminished multigene set of classifier is capable of differentiating post-mastectomy breast cancer patients into the low- and high-risk groups. This new classifier has the potential to spare low-risk N1 patients from radiotherapy and at the same time help identify high-risk N0 patients for radiotherapy.

We previously identified 34 genes of interest (GOI) in 2006 to aid the oncologists to determine whether post-mastectomy radiotherapy (PMRT) is indicated for certain patients with breast cancer. At this time, an independent cohort of 135 patients having DNA microarray study available from the primary tumor tissue samples was chosen. Inclusion criteria were 1) mastectomy as the first treatment, 2) pathology stages I-III, 3) any locoregional recurrence (LRR) and 4) no PMRT. After inter-platform data integration of Affymetrix U95 and U133 Plus 2.0 arrays and quantile normalization, in this paper we used 18 of 34 GOI to divide the mastectomy patients into high and low risk groups. The 5-year rate of freedom from LRR in the high-risk group was 30%. In contrast, in the low-risk group it was 99% (p < 0.0001). Multivariate analysis revealed that the 18-gene classifier independently predicts rates of LRR regardless of nodal status or cancer subtype.