Abstract PO5-17-09: Event-free survival in HER2-low vs HER2-zero breast cancer patients submitted to neoadjuvant chemotherapy
Authors: Sartori Guilherme , Ramalho Susana , da Silva Leonardo Roberto , Reinert Tomás , Da Rosa Mahira Lopes , Tavares Grazielle Morais , Vasconcelos Vivian , Mantovani Higor , Cabello Ana Elisa Ribeiro Da Silva , Coelho Guilherme , Mandelli Jovana , Zaffaroni Facundo , Cabello César , Barrios Carlos , Graudenz Marcia Silveira 
Published: May 2024

Abstract
Background: Breast cancer (BC) with low expression of HER2 (HER2-low) might constitute a group of tumors with unique clinical and biological characteristics. However, the prognostic impact of HER2-low status vs HER2-zero in terms of pathological complete response (pCR) and event-free survival (EFS) after neoadjuvant chemotherapy (NACT) remains controversial. The aim of this study was to evaluate pCR and EFS rates in HER2-low vs HER2-zero early BC patients treated with NACT. Methods: In this cross-sectional study, we analyzed 565 consecutive patients with HER2-low and HER2-zero early BC submitted to neoadjuvant therapy from 2017 to 2021 in a single academic center. Patients with biopsy-confirmed stage I-III BC, with HER2-low or HER2-zero status, submitted to locoregional therapy after NACT were included. Clinical and pathological characteristics, pathological response, treatment protocol and RFS were analyzed and considered for statistical analysis. HER2-low was defined by IHC 1+, or 2+ ISH non-amplified; HER2-zero was defined by IHC 0. Pathological response was determined locally, and pCR defined as the absence of residual invasive disease with or without ductal carcinoma in situ in the breast and axilla. EFS was defined as the time from diagnosis to distant recurrence, a second primary, or death from any cause, whichever occurred first. Results: 441 patients were included in the analysis, 236 (53.5%) patients with HER2-low tumors, and 205 (46.5%) with HER2-zero tumors. Overall, 279 (63.3%) were estrogen receptor (ER)-positive tumors, and 162 (36.5%) were ER-negative tumors. Among ER-positive tumors, 166 (59.5%) had HER2-low status, and 113 (40.5%) were HER2-zero. For the ER-negative subgroup, the corresponding rates were 70 (43.2%) and 92 (56.8%), respectively. Most patients had stage II-III BC (423/441; 96%), and 20.2% (89/441) had high nodal tumor burden. Many patients received anthracycline- and taxane-based NACT (425/441; 96.4%), and over 90% (148/162; 91.3%) of ER-negative patients received a platinum agent. The overall pCR rate were 18.1%. Among ER+ tumors, pCR rates were 6.4%, 6.0%, and 7.0% in the overall, HER2-low and HER2-zero tumors, respectively. In ER- tumors, the corresponding pCR rates were 38.3%, 35.7, and 40.2%, respectively. The differences in pCR rates between HER2-low and HER2-zero tumors were not statistically significant (ER-positive, p=0.724; ER-negative, p=0.559). After a median follow-up of 42 months, 90 EFS events occurred. In the HER2-low group there were 56 (23.7%) EFS events, and 34 (16.6%) EFS events in the HER2-zero (HR 1.19; 95% CI 0.77-1.82; p=0.427). Among 279 patients in the ER-positive group there were 48 events, 32 in the HER2-low subgroup and 16 in the HER2-zero group (HR 1.16; 95% CI 0.64-2.13; p=0.622). Among 162 ER-negative tumors there were 42 events, 24 in the HER2-low subgroup, and 24 in the HER2-zero subgroup (HR 1.56; 95% CI 0.84-2.88; p=0.158). NACT discontinuation occurred in 86 patients (ER-positive: 45, 16.1%; ER-negative: 41, 25.3%), mainly due to toxicity (anthracycline-taxane: 10.0%; platinum: 11.7%). Disease progression during NACT were reported in 6.8% (30/441) of patients. Conclusions: Our results show similar pCR rates and RFS among HER2-low and HER2-zero early BC patients after standard NACT, which are consistent with the current literature. Despite the predictive role of low HER2 expression in selecting patients for novel antibody-drug conjugates (ADCs) therapy, its prognostic value could not be confirmed.
Citation Format: Guilherme Sartori, Susana Ramalho, Leonardo Roberto da Silva, Tomás Reinert, Mahira Lopes Da Rosa, Grazielle Morais Tavares, Vivian Vasconcelos, Higor Mantovani, Ana Elisa Ribeiro Da Silva Cabello, Guilherme Coelho, Jovana Mandelli, Facundo Zaffaroni, César Cabello, Carlos Barrios, Marcia Silveira Graudenz. Event-free survival in HER2-low vs HER2-zero breast cancer patients submitted to neoadjuvant chemotherapy [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 PO5-17-09.