Biological analysis of HER2 equivocal (2+) cases in primary breast cancer.
e12555 Background: Overexpression and/or amplification of HER2 is observed in 15–20% of all invasive breast cancer cases. Breast cancer patients with HER2 overexpression can benefit from anti-HER2 therapy. HER2 IHC results are generally divided into four values (range, 0 to 3+). The cases with a HER2 (2+) value should be assessed using FISH. The aim of this retrospective study was to evaluate the biological variables and prognosis of HER2 (2+) cases according to the FISH status. Methods: Primary breast cancer patients (n = 5419) were enrolled in this study from January 2002 to September 2019. The factors investigated included nodal status, tumor size, nuclear grade, ER/PgR and HER2 status, p53 overexpression, and the Ki-67 index values. Positive for HER2 is categorized as having a HER2 value of 3 + or FISH amplified in equivocal cases. Results: The HER2 3+ rate in non-invasive carcinoma was higher than the rate in the invasive carcinoma cases (16.4% vs 12.9%; p < 0.0001). The distribution of HER2 IHC status in invasive carcinoma cases was 3+ (12.9%), 2+ (5.8%) and negative (84.3%). The FISH positive rate of the HER2 2+ cases was 57.0 % (158 cases). HER2 positivity significantly correlated with ER/PgR negative, p53 overexpression, higher Ki-67 value and nuclear grade. The FISH positivity of the HER2 2+ cases significantly correlated with PgR negative, p53 overexpression and higher grade. There were significant differences in biological variables between IHC 3+ and 2+/FISH positive, and between IHC 2+/FISH negative and IHC negative. Patients with HER2 3+ had significantly worse disease-free survival (DFS) rates than the cases before the approval of trastuzumab in Japan. However, there was no difference after trastuzumab was approved. Moreover, there was no difference in DFS according to the FISH status in HER2 2+ cases. Conclusions: HER2 positivity indicated a higher degree of malignancy. HER2 2+ had different independent biological characteristics from HER2 negative (0 & 1+) or positive (3+) cases. Therefore, the difference in biology of HER2 2+ cases may influence the prognosis and should be reconsidered in breast cancer cases.