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.
Aim: This review focuses on the metabolism and toxicological implications of these drugs against breast cancer/
Methodology: 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.
Conclusion: 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.