title: Clinical evidence for overcoming capecitabine resistance in a woman with breast cancer terminating in radiologically occult micronodular pseudo-cirrhosis with portal hypertension: a case report.
abstract: BACKGROUND
  We report a case of stage IV breast cancer terminating in an unusual picture of radiologically occult micronodular pseudo-cirrhosis. Contrast-enhanced computed tomography showed no evidence of metastatic breast cancer within the liver. Unlike the few previously reported cases of intrasinusoidal spread of breast cancer, our patient was palliated with a transjugular intrahepatic portosystemic shunt along with salvage chemohormonal therapy. In addition, our patient demonstrated proof of the principle of the dependence of capecitabine (Xeloda) efficacy on dose scheduling as predicted by laboratory studies based on Gompertzian tumor growth and the Norton-Simon hypothesis.
  
  
  METHODS
  We report the case of a 52-year-old Caucasian woman who developed radiological signs of portal hypertension without radiological evidence of hepatic metastasis five years after being diagnosed with metastatic breast cancer. She was receiving chemotherapy for stage IV breast cancer initially thought to be metastatic only to the bones. During salvage therapy with high-dose estradiol (Estradiol valerate), vinorelbine (Navelbine) and bevacizumab (Avastin), she suddenly developed signs of portal hypertension confirmed on computed tomography and by portal and systemic venous pressure measurements. Drug toxicity due to bevacizumab (Avastin) was initially and incorrectly entertained as a cause. The patient underwent palliative transjugular intrahepatic portosystemic shunt and transhepatic venous liver biopsy, which revealed the presence of rapidly progressive and uncontrolled metastatic breast cancer. The new discovery of radiologically occult intrasinusodal hepatic metastases with secondary micronodular cirrhosis was found to be the cause of her sudden onset portal hypertension. The patient's resistance to capecitabine (Xeloda) was reversed by changing the schedule of medication to biweekly 7/7 (7 days ingesting drug alternating with 7 days off drug) from the 14/7 (14 days ingesting drug alternating with a 7 day rest period) day schedule approved by the US Food and Drug Administration.
  
  
  CONCLUSIONS
  This case report demonstrates an unusual presentation of radiographically occult hepatic metastasis from breast cancer palliated with transjugular intrahepatic portosystemic shunt. All patients with advanced breast cancer developing unexpected portal hypertension should be considered candidates for liver biopsy despite normal computed tomography of the liver imaging results. This is the first report of a reversal of clinical resistance to capecitabine (Xeloda) by changing from the schedule of 14/7 day to a biweekly 7/7 day schedule. This suggests that a biweekly schedule may be best for some patients.
authors.affiliation: Glenn Tisman, M,D, Medical Corporation, Bailey Street, Whittier, California, 90601, USA. christa324@gmail.com.
authors.forename: Christa
authors.initials: C
authors.lastname: Fournier
authors.forename: Glenn
authors.initials: G
authors.lastname: Tisman
authors.forename: Robert
authors.initials: R
authors.lastname: Kleinman
authors.forename: Yong
authors.initials: Y
authors.lastname: Park
authors.forename: William D
authors.initials: WD
authors.lastname: Macdonald
references.citation: Cancer Res. 1988 Dec 15;48(24 Pt 1):7067-71
references.pmid: 3191483
references.citation: Radiology. 2002 Dec;225(3):917; author reply 917-8
references.pmid: 12461279
references.citation: J Clin Oncol. 2008 Apr 10;26(11):1797-802
references.pmid: 18398145
references.citation: Oncologist. 2005 Jun-Jul;10(6):370-81
references.pmid: 15967831
references.citation: Arch Pathol Lab Med. 2004 Dec;128(12):1418-23
references.pmid: 15578887
references.citation: Semin Oncol. 1997 Aug;24(4 Suppl 10):S10-3-S10-10
references.pmid: 9275000
references.citation: Eur J Radiol. 2007 Jan;61(1):57-69
references.pmid: 17145154