Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features

Abstract

Purpose: Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features.

Patients and methods: A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory.

Results: Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18).

Conclusion: The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.

Trial registration: ClinicalTrials.gov NCT00003519.

Figures

Fig 1.

(A) Five-year recurrence rates by Recurrence Score (RS) as a categoric variable by nodal status. RS risk categories: low risk is RS less than 18; intermediate risk is RS 18 to 30; high risk is RS ≥ 31. Relationship between RS and recurrence as a continuous variable for (B) all patients with hormone receptor (HR) –positive disease and (C) HR-positive and human epidermal growth factor receptor 2 (HER-2) –negative disease where HER-2–positive disease was excluded. The rug plots above the x-axis show the individual patients with recurrence in black and the individual patients without recurrence in green. The large CIs at higher RS reflect the relatively small number of patients with RS greater than 50. Pts, patients.

Fig 2.

Five-year recurrence probabilities predicted by the integrator using local and central grade. For cases with the same result for local and central grade, the two values are equal (so the points are on the diagonal). Points above the diagonal have a higher risk grade category for central than for local and patients below the diagonal have a higher risk grade category for local than for central.

Fig 3.

Recurrence score risk percentiles compared with the integrator risk percentiles calculated using (A) local grade (correlation coefficient = 0.10) or (B) central grade (correlation coefficient = 0.19).

Fig 4.

Area under the receiver operating characteristic curves (AUC) for (A) Recurrence Score (RS), (B) the integrator using local grade, and (C) the integrator using central grade.

Fig 5.

(A) Relative risk of recurrence by Recurrence Score (RS) within subsets defined by the integrator predicted risk level. The area of the box is inversely proportional to the variance of the log hazard ratio, and the line indicates the CI. (B) Relative risk of recurrence by integrator risk group within subsets defined by RS risk groups. The area of the box is inversely proportional to the variance of the log hazard ratio, and the line indicates the CI. (C) Absolute 5-year risk of recurrence (and 95% CIs) by RS risk group within subsets defined by integrator-predicted risk level. Intermed, intermediate. Absolute 5-year risk of recurrence (and 95% CIs) by RS risk group within subsets defined by integrator predicted risk level.