Breast Cancer Index (BCI) identifies fewer patients with high risk of late recurrence and high likelihood of benefit from extended endocrine therapy with invasive lobular compared to invasive ductal carcinoma

Abstract Background: Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the first and second most common histologic subtypes of breast cancer. Both IDC and ILC present distinguishing clinicopathologic features that contribute to differences in response to treatment and long-term prognosis. BCI is a validated gene expression assay that provides the risk of overall (0-10y) and late (5-10y) distant recurrence (DR) and predicts the likelihood of benefit from extended endocrine therapy (EET). In this analysis, BCI results between groups of HR+ ILC and IDC breast cancer patients were compared. Methods: The BCI Clinical Database for Correlative Studies is an IRB-approved de-identified database containing >50 clinicopathologic and molecular variables from cases submitted for BCI testing in clinical practice (N=19,126). Molecular variables include BCI Prognostic score, HOXB13/IL17BR ratio (H/I), and molecular grade index (MGI). Clinicopathologic variables were abstracted from pathology reports when available. Chi-squared tests and Kruskal-Wallis tests were used to compare categorical and numeric factors, respectively, between IDC and ILC subgroups. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to analyze BCI Predictive performance in the lobular patients from IDEAL study. Results: The current study included 3814 patients submitted for BCI testing during years 4-7 post-diagnosis with available histologic subtype data (80.5% IDC; 13.2% ILC; 3.0% mixed; 3.3% other). Among those with either ductal (n=3072) or lobular (n=504) carcinomas (71% node-negative and 29% node-positive), patients with ILC were older compared to IDC (>70 y: 17% vs 12%). Clinically, ILC was generally less aggressive than IDC (Grade 3: 7% vs 21%; lymphovascular invasion: 9% vs 20%; HER2+: 2% vs 13%; Ki67 % positive stained cells: 29% vs 46%; p< 0.001 for all comparisons), with the exception that ILC had larger tumors than IDC (T2/T3: 46% vs 24%) due to its unique histology. This was consistent with BCI Prognostic results showing fewer ILC patients at high risk for late DR compared to IDC (43% vs 55%, p< 0.001). BCI (H/I) showed a similar trend with fewer patients with High Likelihood to benefit from EET (39% vs 43%) although the difference was not statistically significant (p=0.169). The combination of BCI prognostic and predictive results revealed that more ILC patients were classified as Low Risk/Low Likelihood of benefit (43% vs 38%) and fewer were called High Risk/High Likelihood of benefit (25% vs 35%) (p< 0.001) compared to IDC. The IDEAL BCI translational study included 142 ILC patients with 9.3 years of median follow-up. Similar to the BCI Clinical Database results, ILC was associated with less aggressive disease than IDC (Grade 3: 18% vs 41%; HER2+: 11% vs 24%). 39% and 61% of ILC patients were classified as BCI (H/I)-High and -Low, respectively. Given the small sample size, BCI (H/I)-High showed a non-significant absolute benefit of 11.9% (HR=0.44, 95% CI 0.09-2.14; p=0.298) and BCI (H/I)-Low showed no benefit (HR=2.63, 95% CI 0.70-9.93; p=0.138). An analysis of the 3-way interaction among treatment, biomarker and histology showed a non-significant p-value of 0.28, suggesting BCI (H/I) provides similar predictive information in ILC as in the overall population. Conclusion: BCI identified a smaller proportion of patients with ILC at High Risk of late DR and High Likelihood of benefit from EET compared to IDC. Data from the IDEAL translational study showed that while fewer patients with ILC were identified as BCI (H/I)-High, they still derived similar absolute benefit compared to the overall cohort, while those classified as BCI (H/I)-Low derived no benefit from EET. Citation Format: Otto Metzger, Neeta Parimi, Natalia Siuliukina, Yi Zhang, Kai Treuner, Gerrit-Jan Liefers. Breast Cancer Index (BCI) identifies fewer patients with high risk of late recurrence and high likelihood of benefit from extended endocrine therapy with invasive lobular compared to invasive ductal carcinoma [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-13.