A Case Report of HER2-Amplification in the Breast Without Histological Abnormality

Atypical ductal hyperplasia and low-grade ductal carcinoma in situ (DCIS) are regarded as precursor lesions of estrogen receptor (ER)-positive invasive breast cancer. In HER2-amplified invasive breast cancer, a precursor lesion before DCIS has not yet been described. Here we introduce a case of HER2-positive lobules in the breast without histological abnormality. A 39-year-old premenopausal woman visited a hospital due to identification of microcalcifications on screening mammography. The subsequent biopsy confirmed high-grade DCIS. She underwent wide excision, and a residual high-grade DCIS with a size of 1.4 cm was found. The tumor cells were hormone receptor positive and HER2 negative on immunohistochemical (IHC) staining. Around DCIS, there were terminal duct lobular units (TDLUs) showing strong HER2 positivity on IHC. These HER2-positive lobules were 7 mm away from the high-grade DCIS and was 1.1 mm in size. These HER2-positive lobules showed no histologic abnormality and had no difference compared with the surrounding normal TDLUs. Nevertheless, in addition to showing HER2 overexpression in IHC, HER2 amplification was also identified in HER2 silver in situ hybridization. HER2 amplification plays an important role in breast cancer development, and HER2 amplification is known to occur as an early event in cancer development. There have been studies identifying driver mutations in normal tissues of other organs. These findings suggest that HER2 amplification in the breast without histological abnormality could occur, and the HER2-positive lobules could be "at risk" for transformation into the precursor lesion of HER2-positive breast cancer, although the biological significance of these findings is unclear.