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

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
• estrogen
• HER2-positive breast cancer
• hormones
• metabolism
• pharmacokinetic
• progesterone
• Triple-negative breast cancer

Article highlights

• Estrogens and progesterone (E/P) can influence the absorption, distribution, metabolism, and excretion of cancer drugs (ADME).

• E/P appears to affect metabolism and excretion through the regulation of efflux pumps and cytochromes.

• Limited data is available on the effect of E/P on ADME of novel breast cancer drugs.

• The clinical impact of E/P modulation on ADME is not well characterized, but overall unlikely to result in clinically significant pharmacokinetic changes.

• E/P may be accounted in the trade-off of efficacy-safety in selected settings.

Declaration of interest

G Curigliano received honoraria for speaker’s engagement from: Roche, Seattle Genetics, Novartis, Lilly, Pfizer, Foundation Medicine, NanoString, Samsung, Celltrion, BMS, MSD; Honoraria for providing consultancy from: Roche, Seattle Genetics, NanoString; Honoraria for participating in Advisory Board from: Roche, Lilly, Pfizer, Foundation Medicine, Samsung, Celltrion, Mylan; Honoraria for writing engagement from: Novartis, BMS; Honoraria for participation in Ellipsis Scientific Affairs Group; Institutional research funding for conducting phase I and II clinical trials from: Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, BMS, Merck Serono, Merck Sharp Dome, Janssen-Cilag, Philogen, Bayer, Medivation, MedImmune. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.