HER2-LOW SCORE AMONG SPECIAL HISTOLOGICAL TYPES OF TRIPLE-NEGATIVE BREAST CANCER

Background: Recently, the efficacy of the antibody-drug conjugate, trastuzumab deruxtecan, for HER2-low breast cancer led to an absolute increase of 55% in the proportion of patients who could benefit from this HER2-directed therapy. Among triple- negative breast cancer (TNBC), around 30% of the cases are considered HER2-low. Nevertheless, these data are based mainly on invasive breast carcinoma of no special type. The prevalence of HER2-low status in special histological types of TNBC, otherwise, is unknown. Objective: We aimed to describe the prevalence of HER2-low status among special histological types of TNBC. Methods: In this retrospective study, patients with a diagnosis of a special histological type of TNBC treated in a single center from 2009 to 2020 were evaluated. Pathology reports were reviewed to characterize the HER2 score; those with immunohistochemistry (IHQ) +1 or +2 with negative in situ hybridization (ISH) were considered HER2-low. Absolute and relative numbers are presented. Results: Among 132 patients identified with a special histological type of TNBC, 77 had the HER2 score detailed (others had a HER2-negative report, without further details). Most of the patients were HER2-zero, while the frequency of HER2-low status overall was 14.3% (n=11). The most frequent special types in the HER2 detailed cohort were metaplastic (n=49), lobular (n=9), adenoid cystic (n=8), apocrine (n=8), and medullary (n=3). In metaplastic and lobular carcinomas, the proportion of HER2-low cases were 12.2% (n=6) and 11.1% (n=1), respectively. None of the patients with adenoid cystic or medullary carcinomas were HER2-low. Apocrine carcinoma was the only group in which a higher proportion of HER2-low status was observed; among the eight patients with apocrine carcinoma, four were HER2-zero and four were HER2-low (two HER2 IHC +1; two HER2 IHC +2 ISH negative). Conclusions: In special histological types of TNBC, the frequency of HER2-low status is lower than observed overall in the TNBC population. A possible exception is the apocrine carcinoma, in which half of the patients were HER2-low.