Factors predicting late recurrence for estrogen receptor-positive breast cancer

Abstract

Background: Adjuvant endocrine therapy beyond 5 years reduces recurrence in patients with estrogen receptor-positive breast cancer. We have previously shown that immunohistochemical markers (IHC4) and two gene expression profile tests (recurrence score [RS] and PAM50 risk of recurrence [ROR]) are associated with time to distant recurrence, and we have now assessed the value of each of these scores and routine clinical variables for predicting outcome, specifically in years 5 to 10.

Methods: We used univariate and multivariable proportional hazards models to determine the prognostic value of all variables and scores (IHC4, RS, ROR) for distant recurrence, separately in years 0 to 5 and specifically for years 5 to 10 for all patients. All statistical tests were two-sided.

Results: Nodal status and tumor size were at least as strong in years 5 to 10 as in years 0 to 5 (nodal status, years 5-10: χ² = 21.72 vs years 0-5: χ² = 11.08, both P < .001; tumor size, years 5-10: χ² = 10.52 vs years 0-5: χ² = 10.82, both P = .001). Ki67 and the overall IHC4 score were the only statistically significant biomarkers related to distant recurrence univariablely in the 5 to 10 year period (χ² = 8.67, χ² = 13.22, respectively). The ROR score was the strongest molecular prognostic factor in the late follow-up period (χ² = 16.29; P < .001), whereas IHC4 (χ² = 7.41) and RS (χ² = 5.55) were only weakly prognostic in this period. Similar results were seen for all subgroups and for all recurrences.

Conclusions: None of the IHC4 markers provided statistically significant prognostic information in years 5 to 10, except for nodal status and tumor size. ROR gave the strongest prognostic information in years 5 to 10. These results may help select patients who could benefit most from hormonal therapy beyond 5 years of treatment.

Figure 1.

Consolidated Standards of Reporting Trials flow diagram for study numbers. ATAC = anastrozole, tamozifen, alone or in combination; ER = estrogen receptor; H&E = hematoxylin & eosin stain; IHC = immunohistochemical markers; PgR = progesterone receptor; QA = quality assurance; ROR = risk of recurrence; RS = recurrence score.

Figure 2.

Annual hazard rate curves (%) for distant recurrence according to risk group and scores (all split at the median). A) Nodal status/tumor size. B) Immunohistochemical markers (IHC4), recurrence score (RS), and risk of recurrence (ROR) score.

Figure 3.

Kaplan–Meier estimates for distant recurrence according to immunohistochemical markers (IHC4), recurrence score (RS), and risk of recurrence (ROR) score group split at the median value.