Characterization of low HER2 expressions in de-novo metastatic breast cancer

Background De-novo metastatic breast cancer (MBC) represents a distinct entity, characterized by different genomic and prognostic features compared to relapsed MBC. Although evidence suggests that half of all breast cancers show low HER2 expressions, and that HER2 expressions may increase between the early and metastatic stage, little is known on HER2-low expressions features of de-novo MBC. Methods We retrospectively reviewed clinical-pathological data of breast cancer patients consecutively referred to our New Drugs Division (from Jan2014 to Dec2019) with an available pathological analysis of the tumor (on either the primary lesion or a metastatic site). We divided HER2-negative cases by ASCO/CAP 2018 guidelines into an IHC 0 subgroup and a HER2-low subgroup (1+ and 2+/ISH-negative). χ2-test was used for comparisons between categorical parameters. Results 442 breast cancer patients were eligible for the analysis, of whom 17% (N=75) had de-novo MBC. 65% of all de-novo MBC were luminal-like, 20% were HER2-positive and 15% were triple negative. 43% (n=32) of de-novo MBC showed low HER2-expressions, more commonly among luminal-like (49% HER2-low) than triple negative tumors (32% HER2-low), although this difference was not statistically significant (p=0.17). Compared to de-novo MBC, low HER2-expressions were significantly more common in relapsed MBC (57% vs 43%, p< 0.03). By comparing HER2-expression in relapsed MBC based on the site of sampling, HER2-low expression rate did not differ if the biopsy was performed on breast/lymph nodes or in visceral sites (68% vs 58%, p=0.1). No significant difference was found in low HER2-expression between de-novo MBC and early stage breast cancers (43% vs 44%, p=0.98). Conclusions De-novo MBC shows a rate of low HER2-expression comparable with early breast cancer, and significantly lower compared with relapsed MBC. This difference did not appear to be related to the biopsy site. Confirmation of these observations on larger populations of patients is warranted.