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Prognostic Impact of Recurrence Score and Estrogen Receptor Expression in Breast Cancer After 5 Years of Tamoxifen

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Key Points

  • RS risk was significantly predictive of late distant recurrence in patients with higher ESR1 expression.
  • Risk of late distant recurrence was relatively low among all patients with a low-risk RS score.

As reported in the Journal of Clinical Oncology by Wolmark et al, higher 21-gene recurrence score (RS) was strongly predictive of late disease recurrence among patients with high quantitative estrogen-receptor expression (ESR1) receiving tamoxifen for 5 years in two NRG Oncology/NSABP (National Surgical Adjuvant Breast and Bowel Project) studies.

Study Details

The study involved data from patients with stage I or II breast cancer who were chemotherapy/tamoxifen-treated, estrogen receptor–positive, and node-positive (NSABP B-28) and tamoxifen-treated, estrogen receptor–positive, and node-negative (NSABP B-14). The ability of RS to predict late (> 5 years) distant recurrence within high- and low–ESR1-expressing groups was examined.

Late Disease Recurrence

Median follow-up was 11.2 years in the B-28 study and 13.9 years in the B-14 study. RS was low (< 18) in 36%, intermediate (18–30) in 34%, and high (≥ 31) in 30% of 1,065 B-28 patients and low in 51%, intermediate in 22%, and high in 27% of 668 B-14 patients.

Median ESR1 expression was 9.7 normalized expression cycle threshold units (CT) in B-28 patients and 10.7 CT in B-14 patients. Among the B-28 patients, RS risk group was associated with a distant recurrence risk over 0 to 5 years (P < .001) and over 5 to 10 years (P = .02) irrespective of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in the B-28 cohort.

With use of this cut point in the B-14 cohort, RS was a significant predictor of late distant recurrence among patients with higher ESR1 expression, with rates over 5 to 15 years of 6.8% in the low-risk, 11.2% in the intermediate-risk, and 16.4% in the high-risk RS groups (P = .01).  Use of the cut point in the B-28 cohort showed that RS risk was associated with distant recurrence risk up to 5 years in lower and higher ESR1–expression groups and only in the higher ESR1–expression group after 5 years (P = .001).

The investigators concluded: “For [late distant recurrence], RS is strongly prognostic in patients with higher quantitative ESR1. Risk of [late distant recurrence] is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis.”

The study was supported by the National Cancer Institute, the National Cancer Institute Community Oncology Research Program, Susan G. Komen for the Cure, Bristol-Myers Squibb Pharmaceutical Research Institute, AstraZeneca, and Genomic Health.

Eleftherios P. Mamounas, MD, of UF Cancer Center at Orlando Health, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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