In this single-institution retrospective analysis, we identified 106 metastatic breast cancer patients with pseudocirrhosis on radiology reports within a 13-year interval. To our knowledge, this is the largest series to date; because pseudocirrhosis was diagnosed by a random radiologist, we postulated that these image changes would be conspicuous rather than subtle. In other words, the actuarial patient number may be higher if a systemic image review is performed. Pseudocirrhosis can be complicated by pHTN[13,15,16,18,26–33]. In contrast to earlier studies that have used imaging criteria to define pHTN, we chose a stringent criterion to define pHTN: the presence of varices on EGD. Despite the use of this criterion, up to 30% of patients (n = 32) were identified as having pHTN, and this too is the largest case series thus far. Oliai et alretrospectively analyzed a consecutive cohort at the University of California Los Angeles and reported that 37 of 199 consecutively treated patients with metastatic breast cancer developed pseudocirrhosis, and of patients with liver metastases, 55% developed pseudocirrhosis . According to that report, pseudocirrhosis in metastatic breast cancers is not rare. However, the term “pseudocirrhosis” is sometimes misleading because some of these patients have hepatic decompensation.
Although our study did not focus on the risk factors and etiologies of pseudocirrhosis, our findings are consistent with those in a series reported by Oliai et al . In their series, they found that pseudocirrhosis does not occur in the absence of liver metastases, and those who developed pseudocirrhosis had received more lines of systemic treatments; they thus concluded that higher cumulative exposure to systemic treatment may be causative in contrast to the previous assumption that pseudocirrhosis is an adverse effect of a particular therapeutic agent. In our cohort, every patient had preceding liver metastases, 76% had bilateral lobe involvement, and 61% had at least 5 hepatic nodules upon liver metastases. In the entire cohort, 69% had received 5 or more lines of chemotherapies, and among patients who were HR+, 68% had received 2 or more lines of endocrine therapy. The median time from the diagnosis of metastatic disease to the development of pseudocirrhosis was 27 (0–108) months, which is in line with the postulation that pseudocirrhosis usually affects patients with considerable pretreatment and is a late event.
In the literature, limited data on the histology change of pseudocrirrhosis are available. In our study, 1 patient had undergone liver biopsy, and the pathology finding was fatty change and fibrosis without malignant cells (Fig. 4). The finding was different from those of Young et aland Diamond et al, who have suggested nodular regeneration hyperplasia or intravascular tumor infiltration with extensive stromal fibrosis and compression of the portal triad vasculature, respectively [13,34]. The pathogenesis may consist of a spectrum and may change along the disease course, which warrants comprehensive research.
Because we defined pHTN by the presence of esophageal or gastric varices in this study, it was unsurprising to find that in addition to triple-negative disease, pHTN is also independently associated with poor OS. Patients with pHTN had significantly more complications of hepatic decompensation, including hyperbilirubinemia, thrombocytopenia, coagulopathy, and hyperammonemia. Moreover, variceal bleeding can be lethal. We summarize data on 25 breast cancer patients with pseudocirrhosis complicated by esophageal or gastric varices in previous case reports and series in Table 4[13,15,16,18,26–33]. Most of these patients had HR+/HER2− disease, and OS was approximately 1 month from the diagnosis of esophageal or gastric varices. In our 32 patients, 23 had GI bleeding episodes, and 11 deaths were associated with variceal bleeding. The median OS of 5 months in this study is congruent with the OS of approximately 1 month reported in previous studies[16,26,30,31]. Poor liver reserve hampered further anticancer treatment. Except for platinum and infusional 5-FU, almost every chemotherapy drug commonly used for breast cancer requires substantial dose modification or is even contraindicated in patients with hepatic dysfunction. This explains why cisplatin and infusional 5-FU were most frequently prescribed after pseudocirrhosis was documented in our study. Furthermore, patients with pHTN may have concomitant ascites, nutrition problems, and resultant poor functional performance. Although managing these patients is challenging, 7 patients with pseudocirrhosis and pHTN had OS exceeding 1 year. Moreover, 5 patients had HR+/HER2−disease, and 2 had HER2+ disease. We believe that effective systemic treatment and aggressive supportive care can prolong the survival of such patients.
The limitations of this study include its retrospective design and the heterogeneous patient sample with different breast cancer subtypes and diverse treatment protocols. The study data were recorded between 2005 and 2017; anticancer drugs approved after 2017 might have improved outcomes. This study evaluated the clinical characteristics and outcomes of patients with breast cancer who had pseudocirrhosis with and without pHTN. Additional studies are warranted to investigate other prognostic factors and chemotherapy dosage regimens as well as the detailed pathogenesis of pHTN in patients with pseudocirrhosis.