Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary.

Abstract

Next-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.

• Authors: Jennifer Shih, Babar Bashir, Karen S Gustafson, Mark Andrake, Roland L Dunbrack, Lori J Goldstein, Yanis Boumber
• Journal: Journal of the National Comprehensive Cancer Network : JNCCN (J Natl Compr Canc Netw) Vol. 13 Issue 8 Pg. 947-52 (Aug 2015) ISSN: 1540-1413 [Electronic] United States
• PMID: 26285240 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2015 by the National Comprehensive Cancer Network.

Chemical References

• Receptor, ErbB-2

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biopsy
• Brain Neoplasms (diagnosis, secondary, therapy)
• Breast Neoplasms (diagnosis, drug therapy, genetics)
• Female
• Gene Amplification
• Genetic Testing
• Humans
• Lung Neoplasms (diagnosis, therapy)
• Mutation
• Neoplasm Staging
• Neoplasms, Second Primary
• Radiography, Thoracic
• Radiosurgery
• Receptor, ErbB-2 (genetics)
• Tomography, X-Ray Computed
• Treatment Outcome