What is the Breast Cancer Index (BCI)?

Breast Cancer Index (BCI): A Prognostic Genomic Assay for Breast Cancer

The Breast Cancer Index (BCI) is a validated genomic assay that combines two molecular profiles—the HOXB13-to-IL17BR expression ratio (H:I ratio) and the Molecular Grade Index (MGI)—to predict both early (0-5 years) and late (5-10 years) distant recurrence risk in hormone receptor-positive, HER2-negative breast cancer patients. 1, 2

Components and Mechanism

• BCI combines the HOXB13-to-IL17BR expression ratio (H:I ratio) and the Molecular Grade Index (MGI) to provide prognostic information beyond conventional clinical factors (age, tumor size, grade, lymph node status) 2, 1
• The H:I ratio has been shown to be prognostic specifically in the setting of adjuvant tamoxifen monotherapy 1
• The addition of MGI to H:I provides additional prognostic discrimination, enhancing the overall predictive power of the BCI assay 2

Clinical Utility and Prognostic Value

• BCI has been validated as prognostic in node-negative breast cancer for both early (years 0-5) and late (years 5-10) distant recurrence 2, 1
• For patients with T1 and T2 node-negative, HR-positive, HER2-negative tumors, a BCI in the low-risk range places the tumor into the same prognostic category as T1a/T1bN0M0 tumors, regardless of tumor size 2
• In a secondary analysis of the TransATAC trial, BCI effectively stratified patients according to their risk of distant recurrence 2
• BCI can identify patients at low risk for late recurrence (beyond 5 years), which is particularly valuable for decisions regarding extended endocrine therapy 3

Risk Stratification

• BCI categorizes patients into low-, intermediate-, and high-risk groups 4
• Low-risk patients have demonstrated less than 3% distant recurrence rate for both 0-5 years and 5-10 years in some studies 2
• In the Stockholm TAM cohort, BCI classified approximately 65% of patients as low risk 3
• In a multi-institutional cohort with larger tumors, 55% of patients were classified as BCI low risk with less than 5% distant recurrence rate for both 0-5 years and 5-10 years 3

Comparison with Other Genomic Assays

• BCI is one of several genomic assays used in breast cancer, alongside Oncotype DX, MammaPrint, EndoPredict, and Prosigna 5
• Unlike MammaPrint, BCI was specifically designed for patients with ER-positive early breast cancer 5
• While Oncotype DX primarily focuses on predicting chemotherapy benefit, BCI provides information on both early and late recurrence risk 6
• Studies have shown approximately 74% concordance between BCI predictive scores and Oncotype DX Recurrence Score 6

Limitations and Evidence Gaps

• There are limited data regarding the role of BCI in node-positive, HR-positive, HER2-negative breast cancer 2, 1
• Most validation studies have focused on postmenopausal women with early-stage disease 4, 7
• The NCCN guidelines note that BCI and other multigene assays provide prognostic and therapy-predictive information that complements TNM staging and biomarker information 2

Special Considerations

• BCI has shown specific prognostic utility in invasive lobular carcinoma, where it independently stratified patients for cumulative risk of 10-year, early, and late distant recurrence 8
• In multivariate analysis of invasive lobular carcinoma, BCI remained the only statistically significant prognostic factor for distant recurrence 8
• BCI can help identify patients who may benefit from extended endocrine therapy beyond the standard 5 years 3, 6

The BCI assay provides valuable prognostic information that can guide treatment decisions, particularly regarding the need for extended endocrine therapy in hormone receptor-positive breast cancer patients.