Abstract PS7-24: Characteristics of HR+/HER2- patients with recurrent disease by HER2 expression from a prospective registry of unresectable locally advanced or metastatic breast cancer: GEICAM/2014-03 (RegistEM)
Authors: Álvarez Isabel , Guerrero Angel , López-Tarruella Sara , Martínez Purificación , Mori Marta , Falo Catalina , Antolín Silvia , Rodríguez César A , Margeli Mireia , Garau Isabel , Tibau Ariadna , Moreno Diana , Cruz Josefina , Echarri María José , Antón Antonio , Rodríguez-Lescure Álvaro , Escudero María José , Bezares Susana , Rojo Federico , Jara Carlos 
Published: February 2021

Background: The RegistEM study is a non-interventional cohort study that will provide prospective data from &gt;1,800 advanced breast cancer (ABC) patients (pts), either after recurrence or as first diagnosis in 38 Spanish sites. Primary objective is the distribution of BC subtypes. A new nomenclature has been proposed for those cases with immunohistochemistry (IHC) 1+ or 2+ and negative in situ hybridization (ISH), HER2-low BC. In clinical practice these tumors are reported as HER2 negative. This subpopulation has been identified as an interesting group from a clinical perspective. Methods: In this analysis (cut-off date 01/April/2020; database is ongoing) we describe the characteristics of 229 pts with hormone receptor (HR)+/HER2-low BC documented in a metastatic lesion after early disease recurrence and who received adjuvant endocrine therapy (ET). Three subgroups of pts have been considered for this analysis based on HER2 results: HER2 IHC 0, HER2-low, and HER2 ISH- (without IHC). Biological samples collection is part of study procedures. Results: The distribution of HER2 IHC 0, HER2-low, and HER2 ISH- subgroups was 52.4%, 42.8% and 4.8%, respectively. The median time to advance disease was 98.6, 88.8 and 106.9 mo in each group. Almost all pts were female and Caucasian (99%), and at ABC diagnosis, 75.5% were postmenopausal. Median age was 59 years (range 33-88). Fourteen (6.1%) pts had HER2+ (IHC 3+ or ISH amplified) BC subtype during their disease. Family history of BC and/or ovarian cancer was reported in 31.4% pts, an hereditary-risk genetic test was performed in 11.4% (n=26) pts in total and BRCA2 gene mutation (n=6) was the only one reported. The most frequent metastases are included in Table 1. Visceral disease was present in 63.3% pts and 76% pts had ≤2 locations. The most frequent 1st-line therapies were ET/biological therapy (BT) (46.7%) and ET (28.8%), and were equal distributed in the 3 subgroups. The most common ET/BT regimens were aromatase inhibitor (AI)/cyclin-dependent kinase 4/6 inhibitor (CDKi) (49.1%/48.9%/42.9% in each subgroup) and fulvestrant (FUL)/CDKi (35.8%/27.7%/28.6%); AIs (50%/64%/66.7%) and FUL (31.6%/20%/0%) were also the most common drugs for monotherapy ET. A 2nd-line therapy was reported in ~53% pts in HER2 IHC 0 and HER2-low, and in 36% pts in HER2 ISH-. The median time to progression (TTP) to 1st-line therapy was 11.4 mo (1.2-37.0), being similar in pts with HER2 IHC 0 and HER2-low (~11 mo), and higher in pts with HER2 ISH- (16 mo). The most frequent 2nd-line therapies were ET/BT (~34% in HER2 IHC 0 and HER2-low, and 25% in HER2 ISH-) [FUL/CDKi (36.4%/47.1%/100%), AI/CDKi (36.4%/23.5%/0%)], chemotherapy as monotherapy (17 pts out of 63 in HER2 IHC 0, 17 pts out of 53 in HER2-low and 1 pt (capecitabine) out of 4 in HER2 FISH-) (capecitabine 29.4%/52.9% in HER2 IHC 0 and HER2-low). Median duration of 2nd-line therapy was ~5 mo in HER2 IHC 0 and ~8 mo in HER2-low and HER2 ISH-; disease progression was reported in 52.4%/62.3%/50% pts, respectively. Conclusions: In this population of HR+ tumors, the proportion of HER2 IHC 0 and HER2-low groups was similar. Time to advance relapse and the distribution of distant metastases were similar among the groups. The most common first- and second-line therapy was the ET/BT combination, with AI/CDKi and FUL/CDKi, respectively.

Table 1Location of metastatic lesionsIHC 0HER2-lowISH- non IHCN=120 N (%)N=98 N (%)N=11 N (%)Bone74 (61.7)55 (56.1)6 (54.5)Liver36 (30.0)37 (37.8)3 (27.3)Lung27 (22.5)21 (21.4)5 (45.5)Lymph Node27 (22.5)21 (21.4)2 (18.2)Soft Tissue6 (5.0)11 (11.2)0CNS3 (2.5)4 (4.1)0Other43 (35.8)31 (31.6)5 (45.5)

Citation Format: Isabel Álvarez, Angel Guerrero, Sara López-Tarruella, Purificación Martínez, Marta Mori, Catalina Falo, Silvia Antolín, César A Rodríguez, Mireia Margeli, Isabel Garau, Ariadna Tibau, Diana Moreno, Josefina Cruz, María José Echarri, Antonio Antón, Álvaro Rodríguez-Lescure, María José Escudero, Susana Bezares, Federico Rojo, Carlos Jara. Characteristics of HR+/HER2- patients with recurrent disease by HER2 expression from a prospective registry of unresectable locally advanced or metastatic breast cancer: GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-24.