A comprehensive update of hormone-related pharmacokinetic variations associated with breast cancer drugs

Expert Opin Drug Metab Toxicol. 2023 Jul-Dec;19(7):389-403. doi: 10.1080/17425255.2023.2244870. Epub 2023 Sep 11.

Abstract

Introduction: Drugs available for the treatment of breast cancer are increasing, yielding improved oncological outcomes. The efficacy and safety of anticancer drugs significantly depend on pharmacokinetic profiles, which could be influenced by several factors, such as sex hormones.

Areas covered: This article discusses the potential hormone-related pharmacokinetic influences on novel breast cancer pharmacotherapies.

Expert opinion: Recently approved drugs for the treatment of breast cancer belong to different classes, each with unique pharmacokinetic profile. The impact of hormones, such as estrogen and progesterone, may occur at different steps of drug metabolism. Key effects of sex hormones ha ve been reported on multidrug-resistant transporters and enzymes involved in the liver metabolism of drugs, such as cytochromes. Nevertheless, no data is currently available to establish hormone-related metabolic interactions that may account for variability in drug scheduling and selection. Whereas we recognize influences may occur, we do not assume hormones alone can yield clinically significant metabolic changes. Rather, we believe that hormonal influences should be considered along with other elements that may affect drugs metabolism, such as concomitant medications, age-related pharmacokinetic changes, and genetic polymorphisms, in order to deliver treatment personalization and ensure better tolerability and safety of anticancer treatments.

Keywords: Breast cancer; HER2-positive breast cancer; Triple-negative breast cancer; estrogen; hormones; metabolism; pharmacokinetic; progesterone.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Breast Neoplasms* / drug therapy
  • Estrogens
  • Female
  • Gonadal Steroid Hormones
  • Humans
  • Polymorphism, Genetic

Substances

  • Estrogens
  • Gonadal Steroid Hormones
  • Antineoplastic Agents