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Updated: Jan 27, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Pathologic Features and Clinical Implications of Breast Cancer With HER2 Intratumoral Genetic Heterogeneity
Kristen E Muller1, Jonathan D Marotti1, Laura J Tafe1
1Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
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.
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