Abstract PO5-13-04: Breast Cancer Index (BCI) results from a HER2 low breast cancer community cohort of operable stage I-II hormone receptor positive (HR+) breast cancer

Abstract Background Hormone receptor positive (HR+) breast cancer (BC) traditionally included HER2-negative or HER2-positive classifications. The BCI test is a quantitative RNA profile assay applied to HR+ early-stage breast cancers from archival pretreatment surgical specimens. The BCI assay estimates the likelihood of distant recurrence (DR) during years 5-10 (prognostic result) and predicts extended endocrine therapy benefit (ETT)(i.e., BCI (H/I)-High, yes benefit) or no benefit (i.e., BCI (H/I)- Low) for patients who have completed 5 years of adjuvant endocrine therapy (AET). Based on the Destiny Breast 04 trial, an antibody drug conjugate (ADC) anti-HER2 therapy was recently approved for treating metastatic HR+HER2 low BCs, which are currently defined as tumors with either HER2 immunohistochemical (IHC) staining of 1+ or IHC 2+ without HER2 gene amplification. Primary archival specimens were eligible for enrollment on the Destiny Breast 04 trial (35%). Quality control of IHC result categories is needed due to new clinical implications in the metastatic setting. To date, BCI results for tumors classified as HER2 low has not been reported. Objectives Determine the average BCI distant DR risk (prognostic result) and the proportion of tumors with BCI (H/I)-High, yes benefit versus BCI (H/I)-Low, no benefit (predictive result) from a small community-based retrospective study of pretreatment samples from a cohort of HER2 low, HR+ breast tumors. Methods Around completion of 5 years of AET, BCI testing was applied to 110 surgically excised archived stage I and 2 HR+ untreated tumors that were collected between 2017 and 2022. Specimens had paired HER2 local pathology IHC and in-situ hybridization (ISH) results. Results 32 tumors were identified as HER2-low including 26 specimens with HER2 IHC 1+ results and six HER2 IHC 2+ tumors with non-amplified HER2 ISH results. Given this was a small exploratory analysis, statistical significance was deliberately not evaluated. Prognostic Results: The average estimated DR risk during years 5-10 was 8% for tumors classified as HER2-low (Range 1.3-17.5%). For 26/32 patients with HER2 IHC1+, the average DR risk was 7.4% (Range 1.3-17.5%). For 6/32 patients with HER2 IHC 2+ and non-amplified HER2 ISH results, the average DR risk was 4.6% (Range 1.6-8.6%). Predictive Results: Of the 32 HER2-low tumors, 15/32 (47%) were BCI (H/I)-High (yes benefit) compared to 17/32 (53%) which were BCI (H/I)-Low (no benefit). Conclusions The prevalence of HER2 low tumors appears to be as high as 67% in reports to date. In this small series, the prevalence of HR+ HER2 low tumors was 29% (32/110). The average DR risk in these HR+ HER2 low cases was roughly 8% which represents a DR risk that is very similar to the average DR risk of 7.4% for HR+ HER2 negative tumors reported from one of the large BCI validation studies (TransATAC). In this series of HER2 low BCs, the proportions of BCI (H/I)-High (yes benefit) and BCI (H/I)-Low (no benefit) tumors were 47% and 53%, compared with 46% and 54%, respectively, in three large BCI validation studies (Trans-aTTom, B42, IDEAL) for HER2 negative tumors. Although this is a small retrospective series, these results suggest that HER2 low tumor are, by BCI testing, very similar to HER2 negative tumors in DR risk (prognostic results). Also, it appears that BCI (H/I)-High (yes benefit) and BCI (H/I)-Low (no benefit) proportions (predictive results) for HER2 low tumors appear similar to reported results for HER2 negative tumors. Follow-up data from larger series are needed to determine if BCI testing is prognostic and predictive for HER-2 low BCs. Citation Format: Milana Dolezal, Mark Pegram. Breast Cancer Index (BCI) results from a HER2 low breast cancer community cohort of operable stage I-II hormone receptor positive (HR+) breast cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-13-04.