title: Eribulin-induced liver dysfunction as a prognostic indicator of survival of metastatic breast cancer patients: a retrospective study.
abstract: Eribulin is a non-taxane, microtubule dynamics inhibitor that increases survival of patients with metastatic breast cancer. Although eribulin is well tolerated in patients with heavily pretreated disease, eribulin-induced liver dysfunction (EILD) can occur, resulting in treatment modification and subsequent poor disease control. We aimed to clarify the effect of EILD on patient survival.
  
  
  
  The medical records of 157 metastatic breast cancer patients treated with eribulin between July 2011 and November 2013 at Cancer Institute Hospital were retrospectively analyzed. EILD was defined as 1) an increase in alanine aminotransferase or aspartate aminotransferase levels >3 times the upper limit of normal, and/or 2) initiation of a liver-supporting oral drug therapy such as ursodeoxycholic acid or glycyron. Fatty liver was defined as a decrease in the liver-to-spleen attenuation ratio to <0.9 on a computed tomography scan.
  
  
  
  EILD occurred in 42 patients, including one patient for whom eribulin treatment was discontinued due to severe EILD. The patients who developed EILD had significantly higher body mass indices (BMIs) than those who did not develop EILD (24.5 vs. 21.5, respectively; P < 0.0001), with no difference in the dose intensity of eribulin between the two groups (P = 0.76). Interestingly, the patients with EILD exhibited significantly longer progression-free survival (PFS) and overall survival (OS) than those without EILD (P = 0.010 and P = 0.032, respectively). Similarly, among 80 patients without liver metastasis, 19 with EILD exhibited significantly longer PFS and OS than the others (P = 0.0012 and P = 0.044, respectively), and EILD was an independent prognostic factor of PFS (P = 0.0079) in multivariate analysis. During eribulin treatment, 18 patients developed fatty liver, 11 of whom developed EILD, with a median BMI of 26.7.
  
  
  
  Although EILD and fatty liver occurred at a relatively high frequency in our study, most of the patients did not experience severe adverse effects. Surprisingly, the development of EILD was positively associated with patient survival, especially in patients without liver metastases. EILD may be a clinically useful predictive biomarker of survival, but further studies are needed to confirm these findings in another cohort of patients.
authors.affiliation: Department of Medical oncology, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. tkobayashi.g@gmail.com.
authors.forename: Takayuki
authors.identifier: 0000-0001-5257-3247
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Medical oncology, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Jyunichi
authors.initials: J
authors.lastname: Tomomatsu
authors.affiliation: Department of Breast Medical Oncology, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Fukada
authors.affiliation: Department of Breast Medical Oncology, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shibayama
authors.affiliation: Department of Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Teruya
authors.affiliation: Department of Breast Medical Oncology, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwase
authors.affiliation: Department of Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Medical oncology, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D056486:Chemical and Drug Induced Liver Injury / Q000000981:diagnostic imaging / Q000453:epidemiology*; D018572:Disease-Free Survival; D005260:Female; D005663:Furans / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007659:Ketones / Q000008:administration & dosage* / Q000009:adverse effects; D008107:Liver Diseases; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides
keywords: Eribulin-induced liver dysfunction; Fatty liver disease; Metastatic breast cancer