Abstract P4-07-38: Real-world data of Advanced Breast Cancer (ABC) patients with HER2-positivity before the second-line therapy: data from the observational study GEICAM/2014-03 (RegistEM)
Authors: López-Tarruella Sara , Guerrero-Zotano Angel , Cruz Josefina , Novoa Silvia Antolin , Martínez Purificación , Hernández María , Rodríguez César A , Chacón J. Ignacio , Tibau Ariadna , Falo Catalina , Rodríguez-Lescure Álvaro , Margelí Mireia , Servitja Sonia , Andrés Raquel , Galán-Gramaje María , Adrover Encarna , Miguel Ana , Villanueva Rafael , Varela Silvia , Campo Ruth , Escudero Mª José , Bezares Susana , Rojo Federico , Álvarez Isabel 
Published: March 2023

Abstract
Background: Over the last years, the treatment of HER2-positive (HER2+) breast cancer (BC) patients (pts) has been changing because of the development of new anti-HER2 agents. In the current analysis, we describe the features, treatment patterns, progression-free survivall (PFS) and overall survival (OS) outcomes of BC pts with HER2 + (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH]+), following ASCO/CAP 2018 guidelines in the most recent tumor lesion before the 2nd-line.
Methods: The RegistEM study is an ongoing BC registry study that is providing prospective data from around 1900 pts diagnosed with advanced BC (ABC) between 01/Jan/2016 and 31/Dec/2019, in 38 Spanish institutions from GEICAM network. In this analysis, 296 HER2+ BC pts have been included, representing the 18% of pts available in the database at the cut-off date (08/Apr/2022), with ABC diagnosis before 2019 (n=1559).
Results: At first ABC diagnosis, 58% (n=173) pts had recurrent disease (&gt;36 months [mo] from initial BC diagnosis in 62%), 41% (n=120) de novo metastatic BC and 1% (n=3) unresectable locally ABC (ULABC); the median age was 58 years, 68% were postmenopausal and there was only 1 male pt. From total 296 pts, 66% had hormone receptor expression [HR+]; the BC subtype was assessed in tumor tissue from the breast (58%) or a metastatic lesion (34%), and in 8% pts, HER2 positivity was observed after the 1st-line. Family history of BC and/or ovarian cancer was reported in 28% pts, and a hereditary-risk genetic test was performed in 26% pts (n=74/282). Germline BRCA1/2 and TP53 genetic testing were reported in 14 and 26 pts respectively, being mutated in 3/14 (21%) and 5/26 (19%) pts. Bone (50%), lymph nodes (49%), liver (35%), lung (31%), soft tissue (8%) and central nervous system (CNS), mostly in brain (8%), were the main metastatic sites. One hundred pts were diagnosed with CNS metastases: 24 at baseline, 48 during the 1st-line and 28 in subsequent lines. Additional data according to HR status and type of ABC are detailed in the table below, showing a worse prognosis in absence of HR expression. In HR- pts, bone metastases were less frequent and lymph nodes metastases more frequent compared to HR+ pts. Visceral disease was present in 69% (66% in HR+ and 74% in HR-; non-statistically significant) pts and ≈80% had ≤3 (54%, ≤2) locations involved. The most common therapies by line were: 1) 1st-line: Chemotherapy (CT) + biological therapy (BT) (38%), CT + BT+ endocrine therapy (ET) (35%), and ET + BT [11%]; 2) 2nd-line: BT (55%), CT + BT (20%) and ET + BT (15%); 3) 3rd-line: CT + BT (49%) and BT (31%). The median (95% confidence interval [CI]) progression-free survival (PFS) on 1st, 2nd and 3rd line was 18 (15-22), 8 (7-9) and 6 (5-8) mo, respectively. The median (95% CI) overall survival (OS) from ABC diagnosis was 43 (40-49) mo. These survival outcomes were higher in HR+ pts, however, the differences were only statistically significant in OS (p=0.006; log-rank). At database cut-off date, death was reported in 47% pts.
Conclusions: In spite of the anti-HER2 therapies administered in the advanced setting, the HR expression is a relevant prognostic factor, with a clinically and statistically significant impact in OS, improving the outcomes of HR+ pts.

Citation Format: Sara López-Tarruella, Angel Guerrero-Zotano, Josefina Cruz, Silvia Antolin Novoa, Purificación Martínez, María Hernández, César A Rodríguez, J. Ignacio Chacón, Ariadna Tibau, Catalina Falo, Álvaro Rodríguez-Lescure, Mireia Margelí, Sonia Servitja, Raquel Andrés, María Galán-Gramaje, Encarna Adrover, Ana Miguel, Rafael Villanueva, Silvia Varela, Ruth Campo, Mª José Escudero, Susana Bezares, Federico Rojo, Isabel Álvarez. Real-world data of Advanced Breast Cancer (ABC) patients with HER2-positivity before the second-line therapy: data from the observational study 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 P4-07-38.