A Novel Breast Cancer Index for Prediction of Distant Recurrence in HR+ Early-Stage Breast Cancer with One to Three Positive Nodes

Abstract

Purpose: The study objective was to characterize the prognostic performance of a novel Breast Cancer Index model (BCIN þ ), an integration of BCI gene expression, tumor size, and grade, specifically developed for assessment of distant recurrence (DR) risk in HR þ breast cancer patients with one to three positive lymph nodes (pN1). Experimental Design: Analysis was conducted in a well-annotated retrospective series of pN1 patients (N ¼ 402) treated with adjuvant endocrine therapy with or without chemotherapy using a prespecified model. The primary endpoint was time-to-DR. Results were determined blinded to clinical outcome. KaplanMeier estimates of overall (0-15 years) and late (!5 years) DR, HRs, and 95% confidence interval (CIs) were estimated. Likelihood ratio statistics assessed relative contributions of prognostic information.Results: BCIN þ classified 81 patients (20%) as low risk with a 15-year DR rate of 1.3% (95% CI, 0.0%-3.7%) versus 321 patients as high risk with a DR rate of 29.0% (95% CI, 23.2%-34.4%). In patients DR-free for !5 years (n ¼ 349), the late DR rate was 1.3% (95% CI, 0.0%-3.7%) and 16.1% (95% CI, 10.6%-21.3%) in low-and high-risk groups, respectively.

Case-Based Review and Clinical Guidance on the Use of Genomic Assays for Early-Stage Breast Cancer: Breast Cancer Therapy Expert Group (BCTEG)

“…[36][37][38] In a further analysis of N1 patients (1-3 positive nodes), a BCI model incorporating tumor size and grade could identify 20% of N1 patients with a low risk of distant recurrence over 15 years (1.3%) who might be safely spared EA ET. 39 Despite these data, however, the panel notes that current ASCO and NCCN guidelines, while supporting use of BCI as a prognostic indicator, do not support its use as a predictive marker for EA ET benefit. [5][6][7] Although not discussed at the meeting, the group also acknowledges that tools such as the Clinical Treatment Score Poste5 Years (CTS5) are available to help inform EA therapy decisions; recent findings have validated this clinicopathologic tool for predicting late recurrence in a large unselected patient population.…”

Genomic Assays in Node Positive Breast Cancer Patients: A Review

“…Some studies have even evaluated use of BCI in ER+ BCA patients who are node +ve with 1–3 +ve LN. BCI gene expression along with tumor size and grade were integrated into a novel Breast Cancer Index model (BCIN+) ( 118 ). This model classified 20% of patients out of a total of 402 with one to three +ve LNs as low risk with a 15-year risk disease recurrence rate of 1.3%.…”

“…This model classified 20% of patients out of a total of 402 with one to three +ve LNs as low risk with a 15-year risk disease recurrence rate of 1.3%. It was concluded that extended endocrine treatment may be spared in this subset of patients ( 118 ). This allowed patients to have a more individualized approach and to be spared the side effects of an additional five years of ET.…”

Considering the biology of late recurrences in selecting patients for extended endocrine therapy in breast cancer

“…In a comparison of all assays in 689 patients from TransATAC, Prosigna was the strongest independent predictor for late recurrence in node-negative breast cancer, while EPclin was the strongest in patients with node-positive disease [53]. The independent prognostic value for late distant recurrence of Prosigna, Breast Cancer Index and EndoPredict has also been demonstrated in other patient cohorts [54][55][56][57][58].…”