Pathologic Features and Clinical Implications of Breast Cancer With HER2 Intratumoral Genetic Heterogeneity.

OBJECTIVES: 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.
METHODS: We retrospectively searched all consecutive invasive breast cancers that underwent HER2 fluorescent in situ hybridization testing and identified cases with HER2 GH.
RESULTS: 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.
CONCLUSIONS: HER2 GH is an infrequent event, may contain morphologic heterogeneity, could infer incomplete response to neoadjuvant therapy, and requires adequate communication with treating clinicians. © American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.