Prolonged Response to HER2-Directed Therapy in Three Patients with HER2-Amplified Metastatic Carcinoma of the Biliary System: Case Study and Review of the Literature

Abstract

HER2 amplification, which results in overexpression of the receptor tyrosine kinase HER2, has been described in a wide variety of malignancies. HER2-targeting agents have been incorporated into the treatment paradigms for HER2-overexpressing breast and gastric cancer. More recently, these agents have shown promise in other gastrointestinal malignancies, such as colon cancer and biliary tract tumors. This study discusses two patients with gallbladder carcinoma and a third with ampullary carcinoma who were able to achieve marked responses to HER2-directed therapy. These cases underscore the importance of molecular analysis for HER2 amplification/HER2 overexpression, irrespective of tumor histology, and highlight a need for further investigation of HER2-directed therapy beyond breast and gastroesophageal cancers. KEY POINTS: Current guidelines recommend molecular assessment for HER2 overexpression exclusively in breast and gastric adenocarcinoma. The focus of this report is on three cases (two biliary tract and one ampullary carcinoma) in which amplification of HER2 or overexpression of HER2 was detected and treatment with HER2-directed therapy resulted in robust responses. These cases exemplify responsiveness of non-breast/gastric histologies to HER2-directed therapies, highlighting several promising new settings for these agents. Testing for amplification of HER2 or overexpression of HER2 should be considered especially in rare diseases with limited treatment options.

Keywords: Ampullary carcinoma; Biliary tract cancer; Gallbladder carcinoma; HER2 amplification; Precision medicine.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

© 2021 AlphaMed Press.

Figures

Figure 1

Serial contrast‐enhanced abdominal computed tomography (CT) scans for case 1 (A, B, C, E, F, G), showing the patient baseline disease prior to initiation of gemcitabine and cisplatin (A, E), progression on gemcitabine and cisplatin (B, F), and response to 5‐Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX) and trastuzumab (C, G). Most recent noncontrast positron emission tomography/CT scan (D, H) shows continued response on 5‐Fluorouracil, Leucovorin, Irinotecan and Oxaliplatin (FOLFIRINOX) and trastuzumab. Yellow arrow: Primary gallbladder adenocarcinoma. Red arrow: Local invasion of gallbladder adenocarcinoma to hepatic segment IV. Blue arrow: Metastatic gallbladder adenocarcinoma to hepatic segment VIII.

Figure 2

Confirmation of HER2 expression hematoxylin and eosin (A1, A2, A3), HER2 immunohistochemical staining (B1, B2, B3), and silver‐enhanced in situ hybridization with chromosome 17 (red) and HER2 expression (black) at 10× magnification (C2, C3), 20× magnification (C1), and 40× magnification (D1, D2, D3). Abbreviations: H&E, hematoxylin and eosin; SISH, silver‐enhanced in situ hybridization.

Figure 3

Serial contrast‐enhanced abdominal computed tomography scans for case 2. Scan showing the patient's baseline disease (A, E), progression on gemcitabine and cisplatin (B, F), and response to trastuzumab (C, G), with sustained response after 1 year of therapy (D, H). Green arrow: metastatic lung nodule. Red arrow: ascites. Yellow arrow: omental carcinomatosis.

Figure 4

Serial positron emission tomography/computed tomography (CT) scans for case 3 showing the patient's baseline disease (A, E), response to Capecitabine and Oxaliplatin (CAPOX) (B, F), and further response to trastuzumab (C, G), with ultimate progression of disease on therapy (D, H). Blue arrow: Fluorine‐18 fluorodeoxyglucose (FDG) avid liver lesions. Green arrow: hepatic segment VI lesion on noncontrast abdominal CT. Yellow circle: ascites.