Targeted Therapies in HER2-Positive Breast Cancer - a Systematic Review

Abstract

About 20% of all breast cancer patients have a human epidermal growth factor receptor 2 (HER2)-positive breast tumor. This entity underwent an impressive change in prognosis, with notable improvement of progression-free survival and overall survival. Due to more aggressive tumors and no specific therapy, HER2 overexpression was historically seen as a negative prognostic marker, with worse prognosis and increased risk of recurrent disease. Trastuzumab, the first anti-HER2 antibody, revolutionized the systemic therapy options in HER2-positive breast cancer and initiated several targeted therapies and more personalized treatment strategies. Over the years, multiple HER2-targeting drugs stepped into clinical practice, for the curative as well as the metastatic situation. This review summarizes the targeted treatment options in HER2-positive breast cancer and their current impact in the clinical routine. Results of the most outstanding trials in HER2-targeted therapies and important ongoing trials are subsequently described for an up-to-date overview.

Keywords: Dual HER2 blockade; HER2-positive breast cancer; Targeted therapies.

Fig. 1

Summary of major adjuvant trials. A = Doxorubicin, C = cyclophosphamide, CHT = chemotherapy, D = docetaxel, H = trastuzumab, L = lapatinib, P = paclitaxel, RT = radiotherapy, qw = weekly administration, q3w = every 3 weeks, w = week.

Fig. 2

Summary of major neoadjuvant trials. E = Epirubicin, C = cyclophosphamide, D = docetaxel, FEC = 5-fluorouracil, epirubicin and cyclophosphamide, H = trastuzumab, L = lapatinib, w = weeks.

Fig. 3

Summary of major metastatic trials. CHT = Chemotherapy, D = docetaxel, H = trastuzumab, L = lapatinib, PD = progressive disease, qw = weekly administration, q3w = every 3 weeks, T-DM1 = trastuzumab emtansine.