Abstract P1-07-18: Clinicopathologic and molecular correlates of breast cancer index (BCI) results in patients with HR+, LN- breast cancer that are high risk of late distant recurrence (DR) / low likelihood of benefit from extended endocrine therapy (EET)
Authors: Royce M , Poage G , Israel MA , Schnabel CA , Holmes FA 
Published: February 2018

Background: BCI is a gene expression assay for patients with early stage HR+ breast cancer that provides 2 results: BCI Predictive, based on the HoxB13/IL17BR (H/I) ratio, reports a prediction of high vs low likelihood of benefit from EET; BCI Prognostic, based on the algorithmic combination of H/I and a set of proliferation-based genes, reports the risk of late distant recurrence (DR). Clinical actionability is distinct based on the 4 possible combinations of prognostic and predictive results. To better characterize patients classified by BCI as having a high risk of late DR but a low likelihood of benefit from EET, we assessed clinicopathologic and molecular correlates in this subset.

Methods: The BCI Clinical Database for Correlative Studies is a de-identified database containing &gt;50 clinicopathologic and molecular variables from cases submitted for BCI in clinical practice (N=19,126). Clinicopathologic variables abstracted from pathology reports were available for a subset of these cases. Molecular proliferation status (molecular grade index [MGI]) and clinicopathologic parameters were examined in the 4 possible BCI result categories of BCI Prognostic (High vs Low risk) and BCI Predictive (High vs Low H/I). Chi-squared tests and ANOVA were used to compare BCI results within subsets.

Results: Analyses included 3843 LN- pts with clinicopathologic data: Median age was 59.1y (range 26-89y; 74% ≥50y); 30.9%, 51.7%, and 17.4% were Grade 1, 2, and 3, respectively; 27.8%, 48.9%, 21.7%, and 1.6% were T1a/b, T1c, T2, and T3, respectively. BCI categorized 41.4% of pts as having Low risk/Low likelihood of benefit, 31.3% with High risk/High benefit, 18.0% with High risk/Low benefit, and 9.3% with Low risk/High benefit. Patients with High Risk/Low Benefit had increased median proliferation scores (MGI), and a greater proportion of pts with grade 2/3 tumors and high Ki67 scores compared to pts with Low Risk/Low Benefit (P&lt;.0001 for all). In contrast, there were only modest differences in clinicopathologic parameters between patients with High Risk/ Low Benefit and those with High Risk/High Benefit.

Conclusion: In characterizing the molecular and clinical correlates in BCI cases with a high risk of late DR but low likelihood of benefit from EET, we found that higher proliferative status was associated with classification of high risk of DR. Future studies might investigate whether patients with this molecular pattern might benefit from combinatorial therapy (e.g., CDK 4/6 inhibitors) with EET. This study highlights the importance of predictive biomarkers for individualized EET therapy recommendation.

Citation Format: Royce M, Poage G, Israel MA, Schnabel CA, Holmes FA. Clinicopathologic and molecular correlates of breast cancer index (BCI) results in patients with HR+, LN- breast cancer that are high risk of late distant recurrence (DR) / low likelihood of benefit from extended endocrine therapy (EET) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-18.