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. 2022 Oct 14;28(20):4435-4443.
doi: 10.1158/1078-0432.CCR-22-0619.

Clinical Validation of EndoPredict in Pre-Menopausal Women with ER-Positive, HER2-Negative Primary Breast Cancer

Anastasia Constantinidou  1   2   3 , Yiola Marcou  2 , Michael S Toss  4 , Timothy Simmons  5 , Ryan Bernhisel  5 , Elisha Hughes  5 , Braden Probst  5 , Stephanie Meek  5 , Eleni Kakouri  2 , Georgios Georgiou  6 , Ioanna Zouvani  6 , Gabriella Savvidou  1 , Vanessa Kuhl  7 , Jennifer Doedt  7 , Susanne Wagner  5 , Alexander Gutin  5 , Thomas P Slavin  5 , Jerry S Lanchbury  5 , Ralf Kronenwett  7 , Ian O Ellis  4 , Emad A Rakha  4
Affiliations

Clinical Validation of EndoPredict in Pre-Menopausal Women with ER-Positive, HER2-Negative Primary Breast Cancer

Anastasia Constantinidou et al. Clin Cancer Res. .

Abstract

Purpose: The EndoPredict prognostic assay is validated to predict distant recurrence and response to chemotherapy primarily in post-menopausal women with estrogen receptor-positive (ER+), HER2- breast cancer. This study evaluated the performance of EndoPredict in pre-menopausal women.

Experimental design: Tumor samples from 385 pre-menopausal women with ER+, HER2- primary breast cancer (pT1-3, pN0-1) who did not receive chemotherapy in addition to endocrine therapy were tested with EndoPredict to produce a 12-gene EP molecular score and an integrated EPclin score that includes pathologic tumor size and nodal status. Associations of molecular and EPclin scores with 10-year distant recurrence-free survival (DRFS) were evaluated by Cox proportional hazards models and Kaplan-Meier analysis.

Results: After a median follow-up of 9.7 years, both the EP molecular score and the molecular-clinicopathologic EPclin score were associated with increased risk of distant recurrence [HR, 1.33; 95% confidence interval (CI), 1.18-1.50; P = 7.2 × 10-6; HR, 3.58; 95% CI, 2.26-5.66; P = 9.8 × 10-8, respectively]. Both scores remained significant after adjusting for clinical factors in multivariate analysis. Patients with low-risk EPclin scores (64.7%) had significantly improved DRFS compared with high-risk patients (HR, 4.61; 95% CI, 1.40-15.17; P = 4.2 × 10-3). At 10 years, patients with low-risk and high-risk EPclin scores had a DRFS of 97% (95% CI, 93%-99%) and 76% (95% CI, 67%-82%), respectively.

Conclusions: The EPclin score is strongly associated with DRFS in pre-menopausal women who received adjuvant endocrine therapy alone. On the basis of these data, pre-menopausal women with EPclin low-risk breast cancer may be treated with endocrine therapy only and safely forgo adjuvant chemotherapy.

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Figures

Figure 1. Distant recurrent-free survival over 10 years by EPclin Score for (A) the full cohort (B) node-negative patients and (C) node-positive patients.
Figure 1.
Distant recurrence–free survival over 10 years by EPclin Score for (A) the full cohort, (B) node-negative patients, and (C) node-positive patients.
Figure 2. Distant recurrent-free survival over 10 years by EP molecular score for (A) the full cohort (B) node-negative patients and (C) node-positive patients.
Figure 2.
Distant recurrence–free survival over 10 years by EP molecular score for (A) the full cohort, (B) node-negative patients, and (C) node-positive patients.
Figure 3. Distant recurrent-free survival over 10 years by EPclin Score for (A) patients who were not treated with ovarian function suppression (OFS) and (B) patients who were treated with OFS.
Figure 3.
Distant recurrence–free survival over 10 years by EPclin Score for (A) patients who were not treated with ovarian function suppression (OFS) and (B) patients who were treated with OFS.
See this image and copyright information in PMC

References

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