Abstract P1-05-05: Prognostic value of HER2 expression levels in non-metastatic triple-negative breast cancer and correlation with other biomarkers
Authors: William Jacot, Aurélie Maran-Gonzales, Oceane Massol, Charlotte Sorbs, Caroline Mollevi, Séverine Guiu, Florence Boissière-Michot, Jeanne Ramos
Journal: Cancer Research (2022)

Abstract Background: HER2 low breast cancer (BC), presenting 1+ or 2+ (without gene amplification) IHC staining, is an emerging subtype due to dedicated treatments that are now tested. Very few data have been reported on this specific subtype, especially in the triple-negative breast cancer (TNBC) group. Our aim was to evaluate HER2 expression and its prognostic value in a large retrospective series of patients with non-metastatic TNBC and a long follow-up, characterized for Basal-like (BL) or molecular apocrine-like (MA) IHC profiles as well as TILs infiltrate, PDL1 expression and PIK3CA/PTEN mutations. Patients and methods: HER2 expression (0, 1+, 2+) was evaluated on the clinical sample with the HercepTestTM immunohistochemical (IHC) assay, using the 2018 ASCO-CAP guidelines for HER2 scoring, in a series of 296 patients with non-metastatic TNBC treated in our center between 2002 and 2012. HER2 2+ IHC cases were evaluated by FISH and amplified cases were excluded. BL and MA profiles were defined as IHC CK5/6 and/or EGFR expression, and Androgen-receptor and FOXA1 IHC expression, respectively, in a previously used Tissue MicroArray. HER2 expression levels were tested for their association with baseline clinicopathological variables, and for Relapse-Free Survival (RFS) and Overall survival (OS). Results: A total of 296 TNBC tumors was selected for this analysis (248 HER2=0 (83.8%), 40 HER2=1+ (13.5%), 8 HER2=2+ (2.7%)). Considering these percentages, HER2 1+ and 2+ cases were grouped for statistical analysis. Median age was 57.7 years (range 28.5-98.6). 45.8% of tumors were classified pT1 and 63.5% pN0. We found 81.9% of patients had ductal carcinomas, 5.5% lobular carcinomas and 12.6% other histological types. Histological grade 1-2 represented 21% of all tumors. A BL phenotype was observed in 63.8% of cases, and an MA profile in 40.2% of the cases. Adjuvant chemotherapy (ACT) was delivered in 75.3% of patients. Compared to HER2 0 tumors, HER2 1+/2+ tumors exhibited a lower nuclear grade (1/2) (35.4% vs. 18.2%, p=0.007) and MA profile (57.5% vs. 36.7%, p=0.008). With a median follow-up of 9.7 years, HER2 2+ tumors (compared to HER2 0/1+ tumors) were associated, in univariate analysis, with a worse RFS (HR=3.16, 95%CI [1.27; 7.85], p=0.034). No statistically significant OS or RFS difference was found when using the HER2 0 vs. 1+/2+ grouping. Multivariate analyses results are summarized in Table 1. Conclusions: HER2 1+/2+ expression is associated with lower histological grade and MA profile, a specific subgroup of TNBC with a worse prognosis. Considering the current development of anti-androgens for MA tumors and anti-HER2 antibody-drug conjugates in this HER2 1+/2+ population, this clinicopathological association could have therapeutic implications. While rare (2.7% of cases in our series), HER2 2+ TNBC seems to be affected with a worse RFS, advocating for a dedicated evaluation of this subgroup. VariablesOS (N=263)RFS (N=285)HR95% CIP-valueHR95% CIP-valueTumor size &amp;lt;0.001 T11 T2/T3/T42.551.49 – 4.37 Nodal status 0.004 &amp;lt;0.001N-11 N+2.011.26 - 3.224.472.71 - 7.37HistologyDuctal10.001Other0.340.16 – 0.72Adjuvant chemotherapy &amp;lt;0.001 0.001No11 Yes0.330.21 - 0.530.400.24 - 0.66Molecular Apocrine profileNo10.041Yes1.611.02 – 2.54TILs (%) 0.024 0.002≤ 51 1 &amp;gt; 5 0.570.34 – 0.95 0.440.25 - 0.77HER2 (0 vs 1+/2+)010.46610.3001+/2+0.810.45 – 1.451.370.77 - 2.42 Citation Format: William Jacot, Aurélie Maran-Gonzales, Oceane Massol, Charlotte Sorbs, Caroline Mollevi, Séverine Guiu, Florence Boissière-Michot, Jeanne Ramos. Prognostic value of HER2 expression levels in non-metastatic triple-negative breast cancer and correlation with other biomarkers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-05-05.