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Shih J , Bashir B , Gustafson KS , Andrake M , Dunbrack RL , Goldstein LJ , Boumber Y
Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary
J Natl Compr Canc Netw. 2015 Aug;13(8) :947-52
PMID: 26285240 PMCID: PMC4763101 URL: http://www.ncbi.nlm.nih.gov/pubmed/26285240
AbstractNext-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions.
NotesShih, Jennifer Bashir, Babar Gustafson, Karen S Andrake, Mark Dunbrack, Roland L Goldstein, Lori J Boumber, Yanis United States J Natl Compr Canc Netw. 2015 Aug;13(8):947-52.