In a recent phase II trial of afatinib in combination with 3-weekly trastuzumab for the treatment of HER2-positive breast cancer in a neo-adjuvant setting, the dosage of afatinib was reduced to 20 mg every second day for the first 2 weeks and a primary prophylaxis with loperamide was obligatory during the first 4 weeks of treatment. Here, ERBB2 is linked to breast carcinoma.