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

• Published in: Clinical cancer research Vol. 28; no. 20; pp. 4435 - 4443
• Main Authors: Constantinidou, Anastasia, Marcou, Yiola, Toss, Michael S, Simmons, Timothy, Bernhisel, Ryan, Hughes, Elisha, Probst, Braden, Meek, Stephanie, Kakouri, Eleni, Georgiou, Georgios, Zouvani, Ioanna, Savvidou, Gabriella, Kuhl, Vanessa, Doedt, Jennifer, Wagner, Susanne, Gutin, Alexander, Slavin, Thomas P, Lanchbury, Jerry S, Kronenwett, Ralf, Ellis, Ian O, Rakha, Emad A
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 14.10.2022
• Subjects: Antineoplastic Agents, Hormonal - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Chemotherapy, Adjuvant; Female; Humans; Menopause; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Precision Medicine and Imaging; Prognosis; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - therapeutic use; Receptors, Estrogen - genetics
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-22-0619

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. 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. 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. 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.