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Current status of anti-human epidermal growth factor receptor 2 therapies: predicting and overcoming herceptin

Alice Chung1, Xiaojiang Cui, William Audeh

  • 1Department of Surgery, Division of Surgical Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. alice.chung@cshs.org

Clinical Breast Cancer
|July 9, 2013
PubMed

Insights

Trastuzumab is a targeted therapy for HER2-positive breast cancer, but resistance is common. This review explores resistance mechanisms and new drugs to overcome them, highlighting the basal subtype as a risk factor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • HER2-positive breast cancer affects 20-25% of patients and is linked to poor outcomes.
  • Trastuzumab (Herceptin) is effective but faces challenges with primary resistance and acquired resistance in metastatic disease.
  • Resistance to trastuzumab occurs in 60-85% of HER2+ metastatic breast cancer patients.

Purpose of the Study:

  • To review the mechanisms of action and resistance to trastuzumab in HER2-positive breast cancer.
  • To discuss emerging therapeutic strategies aimed at overcoming trastuzumab resistance.
  • To explore the role of the basal molecular subtype as a predictor of risk and resistance.

Main Methods:

  • Literature review of proposed mechanisms of trastuzumab action and resistance.
  • Analysis of current and investigational drugs designed to combat trastuzumab resistance.
  • Examination of studies investigating the basal molecular subtype in HER2+ breast cancer.

Main Results:

  • Trastuzumab targets the HER2 extracellular domain, reducing relapse rates.
  • Significant rates of primary and acquired resistance limit trastuzumab efficacy.
  • The basal molecular subtype is identified as a potential predictor of increased risk and resistance.

Conclusions:

  • Understanding trastuzumab resistance mechanisms is crucial for improving patient outcomes.
  • Development of novel therapeutic agents is essential to overcome resistance.
  • The basal subtype warrants further investigation as a prognostic and predictive marker in HER2+ breast cancer.
Keywords:
Basal molecular subtypeHer2-overexpressing breast cancerResistanceTrastuzumab (Herceptin)

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