Is Prosigna better than Breast Cancer Index (BCI) for determining chemotherapy benefit in postmenopausal women?

Comparison of Prosigna vs. Breast Cancer Index for Determining Chemotherapy Benefit in Postmenopausal Women

Prosigna is not superior to Breast Cancer Index for determining chemotherapy benefit in postmenopausal women with hormone receptor-positive breast cancer, as both tests have distinct clinical applications and neither has been definitively proven superior for predicting chemotherapy benefit specifically. 1

Overview of Gene Expression Assays

• Both Prosigna (PAM50) and Breast Cancer Index (BCI) are validated gene expression assays used to guide treatment decisions in early-stage hormone receptor-positive breast cancer 1
• Prosigna analyzes 50 genes to provide a Risk of Recurrence (ROR) score and classifies tumors into intrinsic molecular subtypes (Luminal A, Luminal B, HER2-enriched, or Basal-like) 2
• Breast Cancer Index (BCI) combines the HOXB13-to-IL17BR expression ratio and molecular grade index to provide prognostic information for both early (0-5 years) and late (5-10 years) recurrence risk 1

Evidence for Prognostic Value

Prosigna (PAM50)

• In the Danish Breast Cancer Cooperative Group database study, Prosigna effectively stratified node-negative patients with a 10-year distant recurrence risk of 5.0% for low ROR versus 17.8% for high ROR 3
• For node-positive patients (1-3 nodes), those with low ROR had a distant recurrence risk of only 3.5% at 10 years compared to 22.1% for high ROR 3
• Prosigna has been validated to provide prognostic information for postmenopausal women with hormone receptor-positive, HER2-negative early breast cancer 2, 3

Breast Cancer Index

• BCI has demonstrated prognostic value for both early (years 0-5) and late (years 5-10) distant recurrence in node-negative breast cancer 1
• BCI provides additional information about extended endocrine therapy benefit, which is not a primary feature of Prosigna 1

Predictive Value for Chemotherapy Benefit

• Neither test has been definitively proven superior specifically for predicting chemotherapy benefit in postmenopausal women 1
• The ESMO guidelines note that gene expression signatures including both Prosigna and BCI "may be used in conjunction with all clinicopathological factors to guide systemic treatment decisions" but do not indicate superiority of one over the other 1
• A direct comparison study between Oncotype DX and Prosigna showed low agreement between the tests, with Prosigna potentially being better at identifying recurrence in the limited cases studied, but this study did not include BCI 4

Clinical Application Considerations

• Prosigna has been studied in special histological subtypes of breast cancer and maintains its prognostic value in these populations 5
• BCI may have an advantage in predicting late recurrence (5-10 years), which could be valuable when considering extended endocrine therapy 1
• The NCCN guidelines mention that "other prognostic gene expression assays may be considered to help assess risk of recurrence based on clinical factors" without specifying superiority of any particular test 1

Limitations and Caveats

• Women younger than 40 are underrepresented in studies evaluating these gene expression signatures 1
• The TAILORx trial, which evaluated Oncotype DX (not Prosigna or BCI), showed that clinical risk factors combined with genomic testing may provide better risk stratification than genomic testing alone 1
• A study comparing Prosigna with Oncotype DX found only 50% agreement between the tests, suggesting that different genomic assays may yield different results for the same patient 4

Practical Approach

• For postmenopausal women with hormone receptor-positive, HER2-negative early breast cancer, either Prosigna or BCI can be used as part of the decision-making process 1
• Consider the specific clinical question: if the primary concern is risk of late recurrence or benefit from extended endocrine therapy, BCI may provide more specific information 1
• If molecular subtyping is important for treatment decisions, Prosigna provides this additional information 2, 3
• The decision should incorporate other clinicopathological factors including tumor size, grade, nodal status, and patient preferences 1