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 .
immunohistochemical stains were strongly positive for ck7 , polyclonal cea , and nuclear cdx-2 . based on the histology and immunostaining
, chemotherapy was initiated with cisplatinum ( 25 mg / m , days 1 and 8) and gemcitabine ( 1,000 mg / m , 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 ( 035 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 ) .
immunohistochemical 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 .
breast 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 . on april 9 , 2013 ,
therapy was started with weekly paclitaxel ( 80 mg / m ) and trastuzumab ( 4 mg / kg loading dose followed by 2 mg / m ) .
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  .
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 .
her-2 is an erbb tyrosine kinase family receptor.1,2 in breast cancer , trastuzumab is approved by the us food and drug administration for use as part of adjuvant and metastatic disease therapy in patients with tumors that overexpress her-2 as measured by immunohistochemistry ( ie , 3 + ) or show her-2 gene amplification by fluorescence in situ hybridization.3,4 trastuzumab is also approved for use in combination with chemotherapy for patients with her2-overexpressing metastatic gastric or gastroesophageal cancers.5 biliary cancers are relatively rare cancers and include adenocarcinomas originating in the gallbladder or bile ducts .
patients randomized to receive gemcitabine and cisplatinum showed a small overall survival benefit of 11.7 months compared with 8.1 months for those receiving gemcitabine alone.6 this combination has consequently become a standard first - line therapy for patients with metastatic biliary cancer .
the cancer in our patient progressed while she received that combination , and there is no proven efficacy of second - line therapy for metastatic biliary cancer .
only about 5% of biliary cancers overexpress her-2.710 ak s gallbladder adenocarcinoma did overexpress her-2 . while there is no formal definition of her-2 3 + in biliary cancers , had her tumor been a breast or gastric cancer , it clearly would have met the criteria for her-2 3 + overexpression , as described above . over the time she received trastuzumab alone , her tumor responded both radiographically and biochemically to trastuzumab alone , with her ca19 - 9 improving from 1,370 u / ml to 432 u / ml and her largest liver lesion decreasing in size from 5.5  3.8 cm to 1.3  0.8 cm , as noted in the radiology ct reports .
a review of the literature identified a single case report of a patient with biliary cancer responding to paclitaxel in combination with trastuzumab,11 but no previous report could be found of a patient responding to trastuzumab as a single agent . in this case ,
. in summary , this metastatic gallbladder cancer was continuing to respond biochemically ( ie , decreasing ca19 - 9 ) and radiographically to trastuzumab alone during the interval between may 20 , 2013 and september 16 , 2013 .
ideally , a study of patients with her-2-overexpressing biliary cancer might confirm the benefit of using trastuzumab in patients with her-2-overexpressing biliary cancer .
 trastuzumab is a monoclonal antibody targeting her-2 . 
 her-2 overexpression has been described in gallbladder cancer and in cholangiocarcinoma . 
 this report describes the first case of a patient with her-2 overexpressing metastatic gallbladder adenocarcinoma and responding radiographically and biochemically to trastuzumab alone . 
Case report
Discussion