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Evolving Therapies for Advanced or Metastatic Hormone Receptor Positive (HR+) Breast Cancer: Pharmacist Interventions that Improve CDK 4/6 Inhibitor Therapy Outcomes – Case 2

INTRODUCTION

About 80% of patients' breast cancers express the hormone receptors (HR) for estrogen (ER) and/or progesterone (PR).1-2 The estrogen receptor is more commonly expressed in patients with breast cancer. Many agents are available for treating women with HR-positive (HR+) breast cancer, including tamoxifen, fulvestrant, and aromatase inhibitors (AIs). Unfortunately, resistance to endocrine therapy readily develops in almost all women. Endocrine therapy resistance takes many forms and involves changes in expression or function of cellular proteins, and includes3-5:

  • Loss of ER expression (15%–20%) or function due to mutation (approximately 1%) or loss of downstream effectors (12%–39%)6-7
  • Gain of growth factor receptor expression (eg, EGFR, HER-2, IGF-1R)
  • Alteration of signaling pathway function (eg, PI3K, ERK, AKT, Pak1)
  • Changes to cell cycle regulators (eg, cyclin D, cyclin E, p21WAF1/CIP1, p27Kip1)

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