Prediction of late distant recurrence (DR) using the Prosigna (PAM50) test in a Danish Breast Cancer Cooperative Group (DBCG) cohort of postmenopausal women diagnosed with hormone receptor-positive (HR+) early breast cancer (EBC) allocated to 5yr of endocrine therapy (ET).

Authors

null

Anne-Vibeke Lænkholm

Department of Pathology, Region Zealand, Denmark

Anne-Vibeke Lænkholm , Maj-Britt Jensen , Jens Ole Eriksen , Torben Kibøll , Birgitte Bruun Rasmussen , Ann S. Knoop , Sean Ferree , Taryn Haffner , Carl Schaper , Bent Ejlertsen

Organizations

Department of Pathology, Region Zealand, Denmark, The Danish Breast Cancer Cooperative Group, DBCG Secretariat, Rigshospitalet, Copenhagen, Denmark, Department of Pathology, Herlev Hospital, Herlev, Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, NanoString Technologies, Inc., Seattle, WA

Research Funding

No funding sources reported

Background: Accurate assessment of the risk of late DR (5-10 yr after surgery) may be used to tailor the duration of ET for patients with HR+ EBC. The Prosigna (PAM50) risk of recurrence (ROR) score was shown to predict late DR for EBC patients treated with 5yr of ET in two randomized clinical trials. Here we assess the ability of PAM50 to predict late DR in a comprehensive nationwide cohort from Denmark consisting of postmenopausal women diagnosed with HR+ EBC allocated to 5yr of ET alone. Methods: Using the population based DBCG database FFPE primary tumor blocks and follow-up data were collected from all HR+ EBC patients diagnosed from 2000-2003 who by nationwide guidelines were allocated to 5yr of ET alone (N = 2749). The PAM50 test was run on the NanoString nCounter Analysis System. Multivariate analyses tested the ability of PAM50 to predict late DR. Patients were categorized as Low, Intermediate, or High risk based upon prespecified ROR cutoffs varied by number of positive nodes. Results: From 2722 included patients, 2164 were disease free at 5yr and analyzed for risk of late DR. Median follow-up was 4.58 years from completion of ET. High risk patients (N = 870) had a late DR risk of 10.2% [95%CI: 8.0-12.7], compared to 6.1% [4.2–8.6] for Intermediate (N = 650) and 2.4% [1.3–4.1] for Low risk patients (N = 644). When ROR was added to a multivariable model including standard clinical and pathological variables it improved the prediction of late DR (likelihood ratio: p < 0.0001; HR for a 20-point change = 1.5 [1.2–1.9]). Luminal B (N = 733, late DR risk = 10.3% [7.8–13.1]) and Her2-enriched patients (N = 132, late DR risk = 8.8% [4.4–15.0]) had a significantly worse outcome than Luminal A (N = 1281, late DR risk = 4.5% [3.3–5.9]), p < 0.0001 for LumB and = 0.034 for Her2e. Conclusions: We have confirmed the ability of Prosigna (PAM50) to predict late DR for HR+ EBC patients regardless of nodal status in a real world cohort devoid of physician selection bias. PAM50 can reliably be utilized to identify patients who need, or most importantly may be safely spared, extended ET beyond 5yr.

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Abstract Details

Meeting

2015 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer—HER2/ER

Track

Breast Cancer

Sub Track

ER+

Citation

J Clin Oncol 33, 2015 (suppl; abstr 544)

DOI

10.1200/jco.2015.33.15_suppl.544

Abstract #

544

Poster Bd #

32

Abstract Disclosures