Marked radiographic response of a HER-2-overexpressing biliary cancer to trastuzumab
AK is a 61-year-old woman who developed right upper quadrant pain and underwent a laparoscopic cholecystectomy on January 22, 2013. Operative findings included a “porcelain” gallbladder, an apparent liver metastasis, and peritoneal metastases. The gallbladder was removed and one liver lesion was biopsied. Pathology confirmed a poorly differentiated gallbladder adenocarcinoma and metastatic liver disease. Immunohistochemical stains were strongly positive for CK7, polyclonal CEA, and nuclear CDX-2. Based on the histology and immunostaining, the pathologist wrote “these findings are consistent with a gallbladder origin”.\nOn February 5, 2013, chemotherapy was initiated with cisplatinum (25 mg/m2, days 1 and 8) and gemcitabine (1,000 mg/m2, days 1 and 8) every 21 days. After two cycles, her CA19-9 had increased from 1,070 U/mL to 3,769 U/mL (0–35 U/mL) and a computed tomography (CT) scan of her chest/abdomen/pelvis showed “interval progression” of her metastatic liver disease (largest liver lesion now 8 × 5 cm).\nImmunohistochemical staining revealed “HER-2 immunostain is strongly positive in the majority of tumor cells”. The pathologist wrote “The clinical significance of this finding in these tumors is unknown”. The pathologist noted that the staining would be the equivalent of 3+ by immunohistochemistry for HER-2 had this been a breast cancer specimen or a gastric cancer specimen.\nBreast and gastric cancers are the only tumors where HER-2 3+ staining is currently defined. The definition of 3+ staining for breast cancer is “very strong, complete, circumferential, membrane staining in 10%–30% of the tumor cells”, and in gastric cancer the definition of 3+ staining is strong, complete, basal lateral, or lateral membranous reactivity that is seen in greater than 10% of tumor cells.\nOn April 9, 2013, therapy was started with weekly paclitaxel (80 mg/m2) and trastuzumab (4 mg/kg loading dose followed by 2 mg/m2). Her CA19-9 improved from 4,143 U/mL on April 9, 2013 to 1,370 U/mL on May 21, 2013. A CT scan on May 20, 2013 showed “interval decrease in the size of the liver metastases”, with the largest lesion having decreased in size from 8.5 × 5 cm to 5.4 × 3.8 cm”. There were no new lesions seen. Paclitaxel therapy was discontinued and the patient has remained on single-agent trastuzumab weekly. By June 26, 2013, her CA19-9 had improved to 432 U/mL and a repeat CT on July 1, 2013 showed “interval decrease in the size of the liver metastases”, with the largest lesion having decreased in size from 5.4 × 3.8 cm to 2.8 × 2.1 cm. She continued to receive trastuzumab alone, and a repeat CT scan on September 18, 2013 showed a further response of her metastatic disease to trastuzumab alone, with the largest liver lesion having decreased in size from 2.8 × 2.1 cm to 1.3 × 0.8 cm. Again, there were no enlarging or new lesions.