title: Metabolism and toxicological implications of commonly used chemopreventive drugs against breast cancer/carcinogenesis.
abstract: BACKGROUND
  Breast cancer has been reported to be among the frequently diagnosed cancer in women worldwide despite advances in early detection and treatment. Several drugs are currently used for chemoprevention as a result of a number of drawbacks associated with breast cancer therapy.
  
  
  OBJECTIVE
  This review focuses on the metabolism and toxicological implications of these drugs against breast cancer/carcinogenesis.
  
  
  METHODS
  Relevant articles on the commonly used anti-breast cancer drugs (raloxifene, tamoxifen, anastrozole, letrozole and exemestane) used in chemoprevention were searched using the major scientific databases including Scopus, Embase, PubMed/ Medline, Sciencedirect and Google Scholar.
  
  
  RESULTS
  The mechanism of action of estrogen receptor modulators are basically mediated via binding to estrogen receptors leading agonistic and antagonistic effects, whereas that of aromatase inhibitors involved the suppression of estrogen concentration in plasma via inhibition or inactivation of aromatase. Both estrogen receptor and aromatase modulators are good candidates for breast cancer chemoprevention, with latter being the most appropriate. However, it has been observed that pharmacodynamics nature of these xenobiotics, often yields some undesirable outcomes after administration which may be linked to resistance and other biological side effects, following phase I/II reactions, bioactivation within and around breast tissue microenvironment vis-à-vis distant tissues. Various findings indicated the manifestation of genotoxicity, organ toxicity and oxidative/nitrosative stress at low, moderate and high doses, thereby complicating the already existing precarious condition. Moreover, interindividual variations were also observed amongst patients, suggesting a critical role of genetic polymorphism. Also, variable side effects including osteoporosis, musculoskeletal events, such as arthralgia and myalgia were found to be predominant.
  
  
  CONCLUSIONS
  The aromatase inhibitors seem to be most appropriate when it comes to application by virtue of their metabolic functions and fates. The reason is that raloxifene and tamoxifen are not the ideal drugs to reduce the incidence of primary invasive breast cancer because their safety and efficacy don't reach the desired optimal agent level. However, adequate care should be taken while prescribing, as well as during and after treatment with constant close monitoring of patients for any possible biochemical and clinical manifestations vis-à-vis the issue of pharmacogenetics.
authors.affiliation: Department of Biochemistry, Ahmadu Bello University, Zaria, Kaduna State, Nigeria. amachida31@gmail.com.
authors.forename: Aliyu
authors.initials: A
authors.lastname: Muhammad
authors.forename: Mohammed Auwal
authors.initials: MA
authors.lastname: Ibrahim
authors.forename: Ochuko Lucky
authors.initials: OL
authors.lastname: Erukainure
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Malami
authors.forename: Hadiza
authors.initials: H
authors.lastname: Sani
authors.forename: Hafsat Abdullahi
authors.initials: HA
authors.lastname: Mohammed