PREVALENCE OF NODE NEGATIVE AND SMALL SIZE TUMORS IN A NATIONAL, RANDOMISED, PHASE III ADJUVANT TRIAL IN HER2 + EARLY BREAST CANCER (SHORT-HER STUDY)

Introduction: Several large randomized trials have shown the superiority of combining trastuzumab with chemotherapy versus chemotherapy alone as adjuvant treatment for HER2+ breast cancer patients. Unfortunately, only a minority of the patients enrolled in these trials were node negative, and virtually none had pT1a,bN0 disease, even though recent data have demonstrated a worse outcome for these small HER2+ tumors versus HER2- cases. It is therefore of interest to know the prevalence of N0 disease and of pT1a,b in patients with HER2+ early breast cancer. We are running a large phase III trial comparing two different trastuzumab durations (Short-HER study). We are reporting the characteristics of patients randomized as of April 2010. Methods: The Short-HER study is phase III, multicentric, Italian trial where 2500 HER2+ breast cancer patients will be randomized to: Arm A (Long) 4 courses of anthracycline based chemotherapy (AC or EC) followed by 4 courses of docetaxel in combination with trastuzumab, followed by 14 additional courses of 3-weekly trastuzumab; or Arm B (Short) 3 courses of 3-weekly docetaxel in combination with weekly trastuzumab followed by FEC x3. Results: 470 patients from 66 Italian centers have been randomized, 229 in arm A (long) and 241 in Arm B (Short). Mean age is 54 years (29 to 76); 68% of the cases have ER+ disease. Regarding stage distribution, among 400 evaluable patients, 34.7% have stage I, 37.3% have stage IIA, 10.5% have stage IIB, and 17.5% have stage III disease. In particular, 51% of the patients have node negative disease, and 6.7% have stage pT1a,bN0 disease. Conclusions: In the largest Italian series of HER2+ patients enrolled in a phase III trial, more than 50% have node negative disease, and around 7% have pT1a,bN0 disease. Given the prevalence of low stage disease, these data reinforce the importance of exploring less intensive, and possibly less toxic, adjuvant trastuzumab regimens. Supported by Agenzia Italiana del FArmaco (AIFA).