Prognostic Value of HER2-Low Expression in Non-Metastatic Triple-Negative Breast Cancer and Correlation with Other Biomarkers

Simple Summary HER2-low breast cancer is an emerging subtype for which very few data are available, especially within the triple-negative breast cancer (TNBC) group. Our aim was to evaluate HER2 expression using the 2018 ASCO/CAP guidelines for HER2 scoring and its prognostic value in a large retrospective series of 296 patients with non-metastatic TNBC. In this large, homogeneous series of patients with early TNBC, HER2 1+/2+ expression was associated with a lower histological grade and molecular apocrine profile, and a specific subgroup of androgen receptor-expressing TNBC with worse long-term prognosis. Considering the current development of anti-androgens for molecular apocrine-like tumors and anti-HER2 antibody-drug conjugates for this HER2 1+/2+ population, this clinicopathological association could have therapeutic implications. Although rare (2.7% of patients in our series), HER2 2+ TNBC seems to have worse relapse-free survival, advocating a dedicated clinical, biological and therapeutic evaluation of this subgroup. HER2-low breast cancer (i.e., HER 1+ or 2+, without gene amplification) is an emerging subtype for which very few data are available, especially within 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 (median age: 57.7 years; range: 28.5-98.6). Among the 296 TNBC samples, 83.8% were HER2 0, 13.5% were HER2 1+, and 2.7% were HER2 2+ (HercepTest(TM) and 2018 ASCO/CAP guidelines for HER2 scoring). CK5/6 and/or EGFR-expressing androgen receptors and FOXA1-expressing tumors were classified as basal-like (63.8%) and molecular apocrine-like (MA, 40.2%), respectively. Compared with HER2 0 tumors, HER2 1+/2+ tumors exhibited a lower histological grade (1/2) (35.4% vs. 18.2%, p = 0.007) and MA profile (57.5% vs. 36.7%, p = 0.008). Moreover, patients with HER2 1+/2+ tumors were older (p = 0.047). After a median follow-up of 9.7 years, HER2 2+ tumors (compared with HER2 0/1+ tumors) were associated with worse relapse-free survival (RFS) (HR = 3.16, 95% CI [1.27; 7.85], p = 0.034) in a univariate analysis. Overall survival (OS) and RFS were not different in the HER2 0 and 1+/2+ groups. HER2 levels were not significantly associated with OS or RFS in a multivariate analysis.

Automated summary

The study evaluated HER2 expression and prognostic value in 296 patients with non-metastatic triple-negative breast cancer (TNBC). It was found that HER2 1+/2+ expression was associated with lower histological grade and molecular apocrine profile, with a subgroup of patients having worse long-term prognosis. The rare HER2 2+ TNBC subgroup showed worse relapse-free survival, emphasizing the need for dedicated evaluation for this group.