Modern possibilities of HER2 positive breast cancer treatment (based on clinical trials)

• Main Authors: I V Kolyadina, I V Poddubnaya
• Format: Article
• Language: Russian
• Published: IP Habib O.N. 2014-12-01
• Series: Современная онкология
• Subjects: t-dm1; breast cancer; her2-positive status; herceptin; adjuvant and neoadjuvant anti-her2-therapy; pertuzumab
• Online Access: https://modernonco.orscience.ru/1815-1434/article/view/26956

This review includes the main steps of anti-HER2-therapy for breast cancer (BC). Up to 30% of breast tumors overexpress epidermal growth factor receptor HER2/neu, and this expression is correlated with poor prognosis and course of the disease. Determination of HER2-status in BC is mandatory for all stages, it is necessary to evaluate the prognosis and development of optimal therapeutic algorithm. The first targeted therapy developed in 1992 for the treatment of HER2-positive BC, has become trastuzumab (Herceptin). The unique mechanism of Herceptin (targeted blockade of HER-dependent signaling pathway, the blockade of the activation of PI3K and MAPK signaling pathway, activation of antibody-dependent cellular cytotoxicity, etc.) and high efficiency have significantly changed the prognosis of HER2-positive BC. The important role of 1-year adjuvant therapy with Herceptin has showed in large international trials (HERA, NSABP B-31, NCCTG 9831, BCIRG 006) for reducing the risk of recurrence (50%) and death (30%) in HER2-positive BC. Neoadjuvant chemotherapy with trastuzumab has studied in the large randomized trials (NOAH, GeparQuattro, GeparQuinto), which has been shown to benefit of Herceptin in the rate of pathological complete response and significant improvement of survival. The effectiveness of Herceptin in metastatic HER2-positive BC has showed in the large studies (M7701, HO648g, BCIRG 007, HERNATA, etc.) The advent of pertuzumab opened new perspectives for the treatment BC: pertuzumab inhibits HER2-receptor dimerization with other HER- receptors (HER1-3) and blocks the HER-mediated signaling pathways, activates of antibody-dependent cellular cytotoxicity. The combination of pertuzumab and trastuzumab blockade provides more HER2-mediated intracellular signaling pathways than either drug alone, which leads to a more pronounced anticancer response. In a large randomized study CLEOPATRA had shown unprecedented results of treatment of metastatic or recurrent BC: the increasing median of overall survival up to 56,5 months, regardless of age, race, the prior treatment, hormone receptor status and location of metastases. The benefit of pertuzumab has shown in old patients, patients with brain metastases, as well as a significant increase in progression-free survival. The new class of anti-HER2-agent - conjugates, appeared last time. Trastuzumab emtanzin (T-DM1) - the first conjugate the targeted monoclonal antibody trastuzumab, cytotoxic chemotherapy agent (DM1) and linker. Antitumor effect of T-DM1 sum of the effects of trastuzumab (targeted blockade of HER-dependent signaling pathway) and targeted delivery of high effective agent (DM1), which causes cell death by disrupting microtubule polymerization and cell cycle arrest. Efficiency T-DM1 has shown to increase disease-free survival, rate and duration of response and overall survival in patients with HER2-positive advanced BC pretreated with taxanes and Herceptin (EMILIA trial). Modern treatment options in HER2-positive BC perfectly combine high efficiency, safety and saved the quality of life.