ALTTO(Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial

INTERVENTION: investigational material(s) Generic name etc : Lapatinib INN of investigational material : Lapatinib Therapeutic category code : 429 Other antitumor agents Dosage and Administration for Investigational material : Lapatinib: Oral control material(s) Generic name etc : Trastuzumab INN of investigational material : Trastuzumab Therapeutic category code : 429 Other antitumor agents Dosage and Administration for Investigational material : Trastuzumab: Oral CONDITION: HER2/ErbB2 positive primary breast cancer PRIMARY OUTCOME: efficacy; To compare disease‐free survival (DFS) in patients with HER2 overexpressing and/or amplified breast cancer randomised to trastuzumab for one year versus lapatinib for one year versus weekly trastuzumab (12 or 18 weeks, according to assigned design) followed by a six‐week washout period followed by lapatinib (28 or 34 weeks, according to assigned design) versus trastuzumab in combination with lapatinib for one year. SECONDARY OUTCOME: safety; To evaluate the safety and tolerability INCLUSION CRITERIA: 1. Age>=18 years 2. Eastern Cooperative Oncology Group (ECOG) performance status=<1; 3. Non‐metastatic operable primary invasive adenocarcinoma of the breast fulfilling the following: a. Histologically confirmed; b. Adequately excised (exceptions: patients who have 'non‐resectable' deep margin invasion are eligible provided they have had or will receive radiotherapy encompassing the region concerned; patients with histologically documented infiltration of the skin (pT4) are eligible provided they have undergone or will receive radiotherapy encompassing the tumour bed); c. Axilla dissected; sentinel node sampling is allowed, provided that axillary dissection follows confirmation of a positive sentinel node; sentinel node sampling alone is NOT acceptable after neoadjuvant chemotherapy (in patients receiving neoadjuvant chemotherapy lymph node status will be considered unknown, regardless of the results of post‐chemotherapy axillary dissection); d. Ax