Abstract P5-02-30: Histology-based survival outcomes in HR+/HER2- metastatic breast cancer treated with targeted therapies plus endocrine therapy based on HER2 expression
Authors: Mouabbi Jason , Raghavendra Akshara Singareeka , Bassett Roland , Hassan Amy , Tripathy Debu , Layman Rachel M. 
Published: March 2023

Background: About 55% of hormone receptor (HR)-positive metastatic breast cancer (mBC) show a low-level expression of human epidermal growth factor receptor 2 (HER2-low). HER2-low is defined as HER2 immunohistochemistry (IHC) expression of 1+ or 2+ with a negative HER2 amplification by in situ hybridization. The efficacy of the antibody-drug conjugate trastuzumab deruxtecan in HER2-low HR+ mBC has been practice changing. However, there are conflicting data on the prognostic value of low HER2-expression in HR+ mBC with some reports showing no impact on prognosis and other showing inferior outcomes in HER2-low patients when treated with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) in combination with endocrine therapy (ET).

Methods: We retrospectively searched for patients treated at MD Anderson Cancer Center with a diagnosis of HR+ treated with ET in combination with a targeted therapy (CDK4/6is, everolimus or alpelisib). Patients were divided into 3 groups: All histologies, ductal histology (IDC) and lobular histology (ILC). We obtained data on demographics, estrogen (ER) and progesterone (PR) receptor status, HER2 expression, menopausal status, treatment duration and survival status. The Kaplan-Meier product-limit method was used to compare progression-free survival (PFS) and overall survival (OS) between the three different groups stratified by HER2 expression (HER2 low versus HER2 0).

Results: We identified 1,649 patients (64% HER2-low, 36% HER2 0) with HR+/HER2- treated with targeted therapy (CDK4/6is, everolimus or alpelisib) in combination with ET. The median age was around 50 years in all groups, 75% were White, 55% premenopausal, 95% ER-positive and 83% PR-positive. 68% were treated with CDK4/6is (919 patients treated in first line (1L) and 202 treated in second line), 30% everolimus and 2% with alpelisib. In the patients who received first 1L CDK4/6is, 70% received an aromatase inhibitor as their ET backbone and 30% received fulvestrant. All the patients who received 1L fulvestrant recurred while on adjuvant AI. PFS and OS were not statistically different between the HER2-low and HER2 0 groups treated with targeted therapies (TT) plus ET or 1L CDK4/6is plus ET regardless of the histology (Table 1).

Conclusion: In this single institution analysis, HER2-low status did not have a significant impact on prognosis in HR+/HER2- mBC treated with TT plus ET or 1L CDK4/6is plus ET.

Table 1. Progression-free Survival and Overall Survival in HR+/HER2- mBC patients treated with targeted therapies (TT) plus endocrine therapy (ET) In patients treated with TT + ET in all histologies (A), in IDC (B) and in ILC (C). In patients treated in 1L with CDK4/6is + ET in all histologies (D), in IDC (E) and in ILC (F)

Citation Format: Jason Mouabbi, Akshara Singareeka Raghavendra, Roland Bassett, Amy Hassan, Debu Tripathy, Rachel M. Layman. Histology-based survival outcomes in HR+/HER2- metastatic breast cancer treated with targeted therapies plus endocrine therapy based on HER2 expression [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 P5-02-30.