Real World Evaluation of the Prosigna/PAM50 Test in a Node-Negative Postmenopausal Swedish Population: A Multicenter Study

Kjällquist U, et al. Cancers June 2022
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Introduction

Adjuvant chemotherapy (ACh) reduces the risk of recurrence and breast cancer (BC)-related death up to one third regardless of any clinical or pathologic factor, such as estrogen receptor (ER) expression 1. Importantly, for postmenopausal women with node-negative ER-positive and Human Epidermal Growth Factor Receptor 2 (HER2)-negative disease, the derived absolute benefit is less pronounced due to the lower absolute risk for disease recurrence. Thus, the selection of patients for ACh, especially in the intermediate risk group, should be balanced between known prognostic factors (for example, tumor size, grade and proliferation) and acute and late toxicities and, importantly, comorbidity.

With the significant advances in the understanding of the underlying complexity and heterogeneity of BC biology 2-4, gene expression profiles (GEP) to select patients with low risk of recurrence have been developed, validated and regulatory approved 5. Several retrospective studies using real-world data have demonstrated a marked decline in adjuvant chemotherapy use, especially in patients with node-negative disease 6-9. Clinical utility has been shown prospectively for two signatures (Recurrence Score and 70-gene assay), with a marked reduction up to 20–35% in chemotherapy usage and no negative effect in long-term survival for postmenopausal patients with ER-positive, HER2-negative BC and low to intermediate risk of gene-expression-based recurrence 10-12. Several of these signatures, including the 70-gene assay/MammaPrint (Agendia Inc., Amsterdam, The Netherlands), Oncotype Dx® recurrence score (RS) (Exact Sciences Corp., Madison, WI, USA), EndoPredict/EPclin (EP, Myriad Genetics Inc., Salt Lake City, UT, USA), and Prosigna®/risk of recurrence (ROR) (Veracyte Inc., South San Francisco, CA, USA) are recommended for clinical use by the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) 7,13-15.

Based on health technology assessment, OncotypeDx® and Prosigna® are both recommended for clinical use in Sweden 16. Prosigna® is an assay that determines the intrinsic subtype and risk of recurrence (ROR) score based on the 50-gene Predictor Analysis of Microarray 50 (PAM50) gene signature and tumor size 17. ROR assigns patients into three risk groups (low, intermediate and high) to predict the long-term risk of distant recurrence in both node-negative and node-positive patients, faring favorably in the limited direct comparisons with other prognostic tools 17-20. Risk signature-guided adjuvant therapy for specific age and anatomical-stage-based subgroups of ER-positive/HER2-negative BC has been recommended by the Swedish national breast cancer guidelines since 2019, but the clinical implementation has been relatively conservative due to concerns regarding risk for undertreatment 21. In addition, the cost-benefit of Prosigna® testing has been judged as uncertain due to lack of national data to estimate the rate of ACh administered in the intended population. As a result, the rate of treatment was assumed to increase due to implementation of Prosigna® testing in the health economic analysis by the The Dental and Pharmaceutical Benefits Agency (Tandvårds- och läkemedelsförmånsverket, TLV) 16. Furthermore, concerns were raised by the Swedish agency for medical technology testing (Medicintekniska produktrådet, MTP) about the added value of Prosigna® in comparison with risk assessment based on routine diagnostics, including Ki67, due to lack of such data 22. The objective of this study was to assess the real-life impact of implementing routine Prosigna® testing in a Swedish multicenter context. The study clarifies some of the concerns and presents a detailed analysis on the impact of treatment based on clinical and biological tumor characteristics.

Study Aim

The objective of this study was to assess the real-life impact of implementing routine Prosigna® testing in a Swedish multicenter context.

Conclusion

We conclude that Prosigna®, when combined with clinicopathological biomarkers (tumor size, Ki67, NHG), adds important clinical utility and improved risk stratification, reduces the use of chemotherapy, but also identifies high-risk ER positive/HER2 negative, N0, postmenopausal patients who would not receive treatment based on only routine clinicopathology.

Conference Materials Prosigna Breast

Real World Evaluation of the Prosigna/PAM50 Test in a Node-Negative Postmenopausal Swedish Population: A Multicenter Study

Kjällquist U, et al. Cancers (Basel). 2022.
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