A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer

TLDR

The likelihood of distant recurrence in node‑negative, estrogen‑receptor‑positive breast cancer patients is poorly defined by conventional clinical and histopathological measures. The study tested whether a reverse‑transcriptase PCR assay of 21 selected genes could predict the likelihood of distant recurrence in tamoxifen‑treated, node‑negative breast cancer patients enrolled in NCTB‑14. Gene‑expression levels of 16 cancer‑related and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and assign patients to low, intermediate, or high risk groups, with adequate RT‑PCR profiles obtained for 668 of 675 tumors. The assay classified 51 % low, 22 % intermediate, and 27 % high risk, with 10‑year distant recurrence rates of 6.8 %, 14.3 %, and 30.5 % respectively, and the recurrence score independently predicted recurrence and overall survival (P < 0.001).

Abstract

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures.We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient.Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients.The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer.