Risk Assessment Using Gene Expression Profiling Correlates with Clinical Prognosis Estimation in Hormone Receptor-Positive/HER2-Negative Early Breast Cancer

Alexa Binder; Kristina Tendl-Schulz; Maximilian Marhold; Kerstin Wimmer; Margaretha Rudas; Rupert Bartsch; Zsuzsanna Bago-Horvath; Elisabeth S Gruber; Ruth Exner

doi:10.1159/000545785

Risk Assessment Using Gene Expression Profiling Correlates with Clinical Prognosis Estimation in Hormone Receptor-Positive/HER2-Negative Early Breast Cancer

Breast Care (Basel). 2025 Apr 14:1-8. doi: 10.1159/000545785. Online ahead of print.

Authors

Alexa Binder¹, Kristina Tendl-Schulz², Maximilian Marhold³, Kerstin Wimmer¹, Margaretha Rudas², Rupert Bartsch³, Zsuzsanna Bago-Horvath², Elisabeth S Gruber¹, Ruth Exner¹

Affiliations

¹ Department of General Surgery, Medical University Vienna and Comprehensive Cancer Center Vienna, Vienna, Austria.
² Clinical Institute of Pathology, Medical University Vienna and Comprehensive Cancer Center Vienna, Vienna, Austria.
³ Division of Oncology, Department of Medicine I, Medical University Vienna and Comprehensive Cancer Center Vienna, Vienna, Austria.

Abstract

Background: Gene expression profiles (GEPs) are recommended for tailoring adjuvant treatment in patients with hormone receptor (HR)-positive/HER2-negative breast cancer (BC) with intermediate clinical and pathological risk. This single-center retrospective study aimed at evaluating the clinical relevance of the additive information provided by GEPs in clinical routine at a tertiary care center.

Methods: From 03/2010 to 07/2019, GEPs by either MammaPrint (MP) or PAM50 of HR-positive/HER2-negative early-stage BC were retrospectively included in the study. Pseudonymized data were processed for statistical analysis. Correlations between clinical and molecular risk markers were calculated. Survival was estimated using the Kaplan-Meier method.

Results: Clinical and molecular risk data were available for 213 patients; complete follow-up data were available for 189 patients. According to GEPs by either MP (n = 69) or PAM50 (n = 144), 67 patients (31.5%) had low, 58 (27.2%) intermediate only in PAM50, and 88 (41.3%) high-risk BC. The MP group showed a higher rate of molecular low-risk tumors, while tumors analyzed by PAM50 were more frequent in a molecular high-risk situation. A significant correlation of proliferation rate and grading with the molecular risk score was observed (p < 0.001 each). Adjuvant chemotherapy was recommended in 87.5% of molecular high-risk tumors but administered in 64.8% only. Interestingly, a worse DFS was detected in the molecular low-risk group compared to the high-risk group (p = 0.55). It may be assumed that this is associated with an advanced tumor stage in these patients.

Conclusion: In HR-positive/HER2-negative BC, proliferation rate as well as tumor grade correlated significantly with risk assessment by GEPs. Despite a high-risk result, chemotherapy is often omitted due to patient-specific factors such as age, comorbidities, or patients' preference. On the other hand, survival with genomic low-risk tumors is likely to be compromised to more advanced stage, questioning the clinical validity of GEPs in these cases.

Keywords: Gene expression profiles; Luminal breast cancer; MammaPrint; Prediction Analysis of Microarray 50.