Breast Cancer Index Predicts Late Recurrences in Patients with ER-Positive Breast Cancer

Audrey Andrews

March 2013, Highlights - Prognostic Tests

The Breast Cancer Index (BCI), a polymerase chain reaction–based assay, can predict late recurrences in estrogen receptor (ER)-positive patients, according to results from the translational arm of the Arimidex, Tamoxifen, Alone or in Combination (TransATAC) trial population.

The BCI performed on primary tumors in node-negative ER-positive patients, who are traditionally considered a “good-risk” group, identifies subgroups with a high risk of recurrence, and its prognostic power works independent of traditional clinical characteristics, such as number of nodes, tumor grade, age, and so forth, reported Dennis C. Sgroi, MD, Asso­ciate Professor, Dana-Farber/Harvard Can­cer Center, Harvard Medical School.

“At the point of diagnosis, BCI identified 2 groups: those at low risk of early recurrence who are adequately treated with endocrine therapy alone, and those at high risk of early recurrence who do not benefit adequately from simple endocrine therapy and who should be considered for additional therapy,” Dr Sgroi reported.

“And at the point of 5-year follow-up, for patients who are disease-free, it identified 2 groups: those at low risk of late recurrence who do not need subsequent therapy, and those at significant risk of late recurrence who should be considered for additional or alternative systemic adjuvant therapy,” he continued.

Dr Sgroi noted that residual risk of recurrence remains a substantial concern for patients with ER-positive breast cancer. Current multigene signatures have significant prognostic performance in predicting early recurrences (ie, up to 5 years after diagnosis); however, such signatures have limited performance in predicting the risk of late recurrence (ie, >5 years), he noted.

The BCI consists of 2 biomarkers: the HOXB13:IL17BR gene-expression ratio and a set of cell cycle–related genes that form the molecular grade index. Investigators compared the prognostic performance of the BCI with the 21-gene Recurrence Score and the immunohistochemical (IHC)4 score in 665 patients from the translational arm of the TransATAC trial who were followed for a median of 10 years.

The index distinguished 3 risk groups—BCI-low (58%), which constituted the reference; BCI-intermediate (25%); and BCI-high (17%). Patients falling into the BCI-intermediate category had nearly a 3-fold increased risk for recurrence at 10 years compared with a 5-fold risk in the BCI-high group (P <.001).

The 5-year rate of late recurrence was approximately 13% for the BCI-intermediate and BCI-high groups compared with 3.5% for the BCI-low group.

The BCI-high group also had more than an 8-fold risk of early recurrence, with 18% of the patients relapsing within 5 years. The BCI-intermediate group rate of patients relapsing by 5 years was 5.6%.

In a multivariate analysis, the BCI outperformed the other 2 tests. “The BCI demonstrated sustained significant prognostic performance, while the IHC4 and Oncotype DX Recurrence Score lost their prognostic ability,” Dr Sgroi added.