title: SLCO1B1*5 polymorphism (rs4149056) is associated with chemotherapy-induced amenorrhea in premenopausal women with breast cancer: a prospective cohort study.
abstract: Because inheritance is recognized as playing a role in age at menarche and natural menopause, the development of chemotherapy-induced amenorrhea (CIA) might depend on inherited genetic factors; however, studies that explore such a correlation are few and have received scant attention. Given the importance of this topic we conducted a comprehensive genotype study in young women (≤45 years) with early-stage breast cancer.
  
  
  
  Our approach tested the effect of variant polymorphisms in drug metabolism enzymes (DMEs) using a predesigned pharmacogenomics panel (TaqMan® OpenArray®, Life Technologies GmbH, Darmstadt, Germany) in premenopausal women (n = 50). Patients received contemporary chemotherapy; in all cases a cyclophosphamide-based regimen with a dose of at least 500 mg/m(2) for six cycles. CIA was considered to be present in women with no resumption of menstrual bleeding within 12 months after completion of chemotherapy or goserelin.
  
  
  
  Twenty-six patients (52 %) showed CIA during follow-up whereas 24 women (48 %) remained premenopausal. Of all the DMEs studied, only the SLCO1B1*5 (rs4149056) genotype was associated with the development of CIA (P = 0.017). Of the 26 patients who were homozygous for the T/T allele SLCO1B1*5, 18 (69.2 %) developed CIA compared with 8 (30.8 %) of the 22 patients who were heterozygous (C/T allele). The association of heterozygous SLCO1B1*5 allele (OR 0.038; 95%CI: 0.05-0.92) with a lower risk of developing CIA remained significant in a binary logistic regression analysis that include age, SLCO1B1*5 allele variants, and goserelin therapy.
  
  
  
  Patient age and SLCO1B1*5 allele variants predict the likelihood of young women with breast cancer developing CIA.
authors.affiliation: Department of Obstetrics and Gynecology, University of Rostock, Klinikum Suedstadt, Suedring 81, Rostock, 18059, Germany. toralf.reimer@med.uni-rostock.de.
authors.forename: Toralf
authors.initials: T
authors.lastname: Reimer
authors.affiliation: Department of Obstetrics and Gynecology, University of Rostock, Klinikum Suedstadt, Suedring 81, Rostock, 18059, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kempert
authors.affiliation: Department of Obstetrics and Gynecology, University of Rostock, Klinikum Suedstadt, Suedring 81, Rostock, 18059, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
authors.affiliation: Institute of Immunology, University of Rostock, P.O.B. 100888, Rostock, 18055, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Thiesen
authors.affiliation: Department of Obstetrics and Gynecology, University of Rostock, Klinikum Suedstadt, Suedring 81, Rostock, 18059, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Institute of Immunology, University of Rostock, P.O.B. 100888, Rostock, 18055, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Koczan
mesh_terms: D000328:Adult; D000367:Age Factors; D000568:Amenorrhea / Q000139:chemically induced* / Q000235:genetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics*; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D027381:Liver-Specific Organic Anion Transporter 1; C503999:SLCO1B1 protein, human; D003520:Cyclophosphamide
keywords: Breast cancer; Chemotherapy-induced amenorrhea; OpenArray genotyping; SLCO1B1; Single nucleotide polymorphism