Breast Cancer Index Identifies Early-Stage Estrogen Receptor–Positive Breast Cancer Patients at Risk for Early- and Late-Distant Recurrence

Abstract

Purpose: Residual risk of relapse remains a substantial concern for patients with hormone receptorpositive breast cancer, with approximately half of all disease recurrences occurring after five years of adjuvant antiestrogen therapy.Experimental Design: The objective of this study was to examine the prognostic performance of an optimized model of Breast Cancer Index (BCI), an algorithmic gene expression-based signature, for prediction of early (0-5 years) and late (>5 years) risk of distant recurrence in patients with estrogen receptor-positive (ER þ ), lymph node-negative (LN À ) tumors. The BCI model was validated by retrospective analyses of tumor samples from tamoxifen-treated patients from a randomized prospective trial (Stockholm TAM, n ¼ 317) and a multi-institutional cohort (n ¼ 358).Results: Within the Stockholm TAM cohort, BCI risk groups stratified the majority ($65%) of patients as low risk with less than 3% distant recurrence rate for 0 to 5 years and 5 to 10 years. In the multi-institutional cohort, which had larger tumors, 55% of patients were classified as BCI low risk with less than 5% distant recurrence rate for 0 to 5 years and 5 to 10 years. For both cohorts, continuous BCI was the most significant prognostic factor beyond standard clinicopathologic factors for 0 to 5 years and more than five years.Conclusions: The prognostic sustainability of BCI to assess early-and late-distant recurrence risk at diagnosis has clinical use for decisions of chemotherapy at diagnosis and for decisions for extended adjuvant endocrine therapy beyond five years. Clin Cancer Res; 19(15); 4196-205. Ó2013 AACR.

Adjuvant Endocrine Therapy for Hormone-positive Breast Cancer, Focusing on Ovarian Suppression and Extended Treatment: An Update

“…The Breast Cancer Index (BCI) is a multi-gene test that identifies the two gene ratio HOXB13:IL17BR (H/I) and the Molecular Grade Index (MGI). A higher distant recurrence-free survival is associated with a low BCI score and is considered as a prognostic value for late recurrence (49). In addition, in TransATAC (translational arm of the Arimidex, Tamoxifen, alone or in combination trial) trial the 21-gene recurrence score assay and the immunohistochemical prognostic model, IHC4, have been shown to be prognostic for early distant recurrence (50).…”

Utility of Molecular Tools for Extended Adjuvant Endocrine Therapy Decisions in Early Breast Cancer

“…The breast cancer index (BCI) is a quantitative reverse transcription polymerase chain reaction-based method that measures the expression of two genes, HOXB13 and IL17BR (H/I) and the proliferation genes, molecular grade index [12]. It was developed in tamoxifen-treated patients with node-negative breast cancer and it has been shown to be useful in prognosticating early and late disease recurrence.…”

Predictive Factors for Late (>5 Years) Distant Recurrences in Hormone Receptor (HR) Positive, Human Epidermal Growth Factor Receptor 2 (HER2) Negative Breast Cancer Patients: >20 Year Follow Up

“…Models such as the Breast Cancer Index (BCI) have been developed and can predict early (0-5 years) and late risk of distant recurrence in early stage breast cancer patients (ER positive and lymph node-negative breast cancer) but these models have not been developed in more advanced breast cancers and furthermore there remains a dearth of studies that have analyzed clinical factors that can predict late recurrence [2]. The aim of this study was to identify clinical and pathological factors at diagnosis that are associated with delayed systemic recurrence in hormone positive (lymph node positive and lymph node negative) breast cancer patients.…”