To review breast cancer with human epidermal growth factor receptor 2 (HER2) genetic heterogeneity (GH), with a focus on clinician interpretation of the results and subsequent management.
We retrospectively searched all consecutive invasive breast cancers that underwent HER2 fluorescent in situ hybridization testing and identified cases with HER2 GH.
Eleven (0.4%) cases of primary breast tumors with reported HER2 GH were identified over 76 months. HER2-positive tumor cells comprised a mean ± SD of 20% ± 15% of the overall tumor population (range, 5%-50%) and exhibited high levels of amplification (HER2/CEP17 = 5.4 ± 2.9). Three cases had morphologic heterogeneity. Of the four patients who completed neoadjuvant chemotherapy, two had trastuzumab; all showed a partial pathologic response. We identified two cases in which there appeared to be clinical misinterpretation of the HER2 results.
HER2 GH is an infrequent event, may contain morphologic heterogeneity, could infer incomplete response to neoadjuvant therapy, and requires adequate communication with treating clinicians.