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The highly effective treatment of human epidermal growth factor receptor (HER) 2-amplified breast cancer has proven challenging because of a signal buffering capacity inherent in the functionally relevant HER2-HER3 target. HER2-HER3 signaling can be inactivated by doses of lapatinib that fully inactivate the HER2 kinase. In mouse models, such doses are not tolerable in continuous administration, but they are tolerable and highly effective in intermittent dosing. We pursued the clinical translation of this treatment hypothesis.

journal of clinical oncology

Phase I Dose-Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer