High accuracy in detecting HER2-low status in FNA of primary and metastatic breast cancer

HER2-positive invasive breast carcinomas (IBCs) account for 15% of breast cancers and are driven by ERBB2 gene amplification. Although historically associated with aggressive behavior, HER2-targeted therapies have significantly improved outcomes. HER2 status is routinely assessed by immunohistochemistry (IHC) and in situ hybridization (ISH). Recently, tumors with low HER2 expression (IHC 1+ or 2+ without amplification), previously classified as HER2-negative, have emerged as a clinically relevant subgroup. Fine-needle aspiration cytology (FNAC) is a minimally invasive alternative to core needle biopsy, particularly useful in inoperable or metastatic settings. FNAC-derived cell blocks (CBs) allow immunocytochemical (ICC) evaluation of biomarkers.

This retrospective study included 46 FNAC-derived CBs from breast cancers (34 primary tumors and 12 metastases) collected at Vanvitelli University Hospital. ICC evaluation of HER2, estrogen receptor (ER), and progesterone receptor (PR) was independently performed by two expert pathologists and compared with corresponding histological assessments. Diagnostic performance was evaluated using sensitivity, specificity, predictive values, concordance rates, and receiver operating characteristic (ROC) curve analysis.

ICC on FNAC-derived CBs showed good diagnostic performance for HER2-low tumors. Sensitivity ranged from 56.3% to 59.4%, whereas specificity was high (85.7%-92.9%). Positive predictive values reached 90.0%-95.0%, whereas negative predictive values were lower (46.2%-50.0%). Concordance between cytological and histological HER2-low assessment exceeded 90%, with ROC area under the curve values of 0.71-0.76. ER showed excellent concordance, whereas PR demonstrated moderate agreement.

FNAC-derived CBs are a reliable tool for identifying HER2-low breast carcinomas when histological samples are unavailable or limited, emphasizing the need for standardized evaluation criteria.