Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary.
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.
From Fox Chase Cancer Center, Temple University Heath System, Philadelphia; Abington Memorial Hospital, Abington; and Molecular Therapeutics Research Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Jennifer
J
Shih
From Fox Chase Cancer Center, Temple University Heath System, Philadelphia; Abington Memorial Hospital, Abington; and Molecular Therapeutics Research Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Babar
B
Bashir
From Fox Chase Cancer Center, Temple University Heath System, Philadelphia; Abington Memorial Hospital, Abington; and Molecular Therapeutics Research Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Karen S
KS
Gustafson
From Fox Chase Cancer Center, Temple University Heath System, Philadelphia; Abington Memorial Hospital, Abington; and Molecular Therapeutics Research Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Mark
M
Andrake
From Fox Chase Cancer Center, Temple University Heath System, Philadelphia; Abington Memorial Hospital, Abington; and Molecular Therapeutics Research Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Roland L
RL
Dunbrack
From Fox Chase Cancer Center, Temple University Heath System, Philadelphia; Abington Memorial Hospital, Abington; and Molecular Therapeutics Research Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Lori J
LJ
Goldstein
From Fox Chase Cancer Center, Temple University Heath System, Philadelphia; Abington Memorial Hospital, Abington; and Molecular Therapeutics Research Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania. From Fox Chase Cancer Center, Temple University Heath System, Philadelphia; Abington Memorial Hospital, Abington; and Molecular Therapeutics Research Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Yanis
Y
Boumber
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D001932:Brain Neoplasms / Q000175:diagnosis / Q000556:secondary / Q000628:therapy; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D005820:Genetic Testing; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000628:therapy; D009154:Mutation; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary; D013902:Radiography, Thoracic; D016634:Radiosurgery; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D018719:Erb-b2 Receptor Tyrosine Kinases