Abstract P4-07-30: Features and survival outcomes of HER2-low patients from a prospective registry of unresectable locally advanced or metastatic breast cancer: GEICAM/2014-03 (RegistEM)
Authors: Álvarez Isabel , Guerrero-Zotano Angel , Tibau Ariadna , Falo Catalina , Hernández María , Miguel Ana , Andrés Raquel , Rodríguez-Lescure Álvaro , Corbellas Miguel , López-Tarruella Sara , Martínez Purificación , Rodríguez Cesar A , Malón Diego , Marin María , Echarri Mª José , Antón Antonio , Cruz Josefina , Moreno Diana , Chacón J. Ignacio , Campo Ruth , Blasco Andrea , Bezares Susana , Rojo Federico , Antolin Silvia 
Published: March 2023

Abstract
Background: HER2-low breast cancer (BC) is a new therapeutic entity, but it is uncertain if this subgroup of BC differs from HER2-negative tumors in clinical characteristics, prognosis, and response to therapy. The objective is to describe the clinical characteristics and outcomes of 422 patients (pts) with HER2-low BC documented before 1st line, having been diagnosed with advanced BC (ABC) before 2019 and included in the RegistEM study (n=1,663).
Methods: In this analysis (cut-off date 08/April/2022; database is ongoing), two subgroups of pts have been considered based on HER2 results: HER2-low (n=422) (immunohistochemistry [IHC] 1+ or IHC 2+ and in situ hybridization [ISH] negative) and HER2-IHC 0 (n=590), as reference. Hormone Receptor (HR) expression has also been considered for subgroup analysis.
Results: At first ABC diagnosis, &lt; 1% pts had unresectable locally advanced BC (ULABC) in both groups, 31% de novo metastatic BC in HER2-low and 20% in HER2-IHC0 groups. Less than 1% were male, 99% Caucasian and ~71% postmenopausal. Median age was 60 years, being similar between both groups (range 26-96). Family history of BC and/or ovarian cancer was reported in 32% pts in HER2-low and 29% in HER2-IHC0. Germline BRCA1/2 mutation was higher in HER2-low (14/40=35%) in reference to HER2-IHC0 (14/64=22%) (p=0.14). Relevant information summarized by HR expression and HER2 status are detailed in the table below. Visceral disease was similar in both total groups (58% in HER2-low vs HER2-IHC0 56%), but slightly higher in HR- HER2-low pts (81% vs 64%), and 84% and 90% pts had ≤3 metastatic locations, in HER2-low and HER2-IHC0 groups, respectively. Distribution of 1st-line therapies was also similar between both groups, being endocrine therapy (ET) plus biological therapy (BT) (HER2-low 39% vs HER2-IHC0 36%) and ET (HER2-low 30% vs HER2-IHC0 28%), while chemotherapy (CT) (HER2-low 13% vs HER2-IHC0 16%) and CT plus BT (HER2-low 9% vs HER2-IHC0 10%) were more frequent in HR- pts. A 2nd-line therapy was reported in 70% HER2-low pts and 67% HER2-IHC0 pts. The median time to progression (TTP) at 1st-line therapy in HER2-low pts was 11 mo (0-66), being similar in HER2-IHC0 pts, but the higher difference was observed in relation to HR expression. Treatments in 2nd-line were similar in both groups, CT and ET/BT were the most frequent totally. Median duration of 2nd-line therapy was ~6 mo; progressive disease (PD) was reported in 85% pts. A 3rd-line therapy was reported in 74% HER2-low and 69% HER2-IHC0 pts. The median time to progression (TTP) to 3rd-line therapy was 6 mo, being similar in HER2-low and HER2-IHC0 pts .The most frequent 3rd-line therapies were CT and ET/BT in both groups, as in 2nd-line. Median duration of 3rd-line therapy was 4 mo; PD was reported in 84% HER2-low pts and 82% HER2-IHC0 pts. Median (95% confidence interval [CI]) PFS at 1st, 2nd and 3rd lines (mo) were 14 (12-16), 6 (5-7) and 6 (5-6) in HER2-low pts, being similar in HER2-IHC0. OS was comparable in all soubgroups analyzed, however, differences were observed regarding HR status.
Conclusions: Our results show that HER2-low BC pts have similar characteristics than HER2-IHC0 BC pts. There are differences in therapy outcomes in terms of survival and prognosis, particularly in HR- tumors, being better in HER2-low BC pts. It could be related to the fact that these tumors have a specific biology, but more evidence is needed.

Citation Format: Isabel Álvarez, Angel Guerrero-Zotano, Ariadna Tibau, Catalina Falo, María Hernández, Ana Miguel, Raquel Andrés, Álvaro Rodríguez-Lescure, Miguel Corbellas, Sara López-Tarruella, Purificación Martínez, Cesar A Rodríguez, Diego Malón, María Marin, Mª José Echarri, Antonio Antón, Josefina Cruz, Diana Moreno, J. Ignacio Chacón, Ruth Campo, Andrea Blasco, Susana Bezares, Federico Rojo, Silvia Antolin. Features and survival outcomes of HER2-low patients from a prospective registry of unresectable locally advanced or metastatic breast cancer: GEICAM/2014-03 (RegistEM) [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 P4-07-30.