Systemic treatment of HER2-positive breast cancer. Part II
Affiliation and adress for correspondence

Klinika Chemioterapii Nowotworów Katedry Onkologii Uniwersytetu Medycznego w Łodzi.
Kierownik Kliniki: dr hab. n. med. Piotr Potemski, prof. UM
Correspondence to: Szpital Specjalistyczny im. M. Kopernika w Łodzi, ul. Paderewskiego 4, 93-509 Łódź, tel.: 42 689 54 31, faks: 42 689 54 32
Source of financing: Department own sources

CURR. GYNECOL. ONCOL. 2012, 10 (1), p. 10-24
ABSTRACT

HER2-positive breast cancer is associated with an aggressive clinical course and poor prognosis. At present, these patients may be offered targeted therapies directed against a specific molecular target, i.e. HER2 receptor. Standard agents of this class include trastuzumab (monoclonal antibody) and lapatinib (small-molecule inhibitor of HER2-receptor-associated tyrosine kinase). As estimated, about 25% of breast tumors are HER2-positive, and these patients are candidates for trastuzumab therapy. A precondition for initiation of the treatment is confirmation of overexpression of HER2 protein or amplification of HER2 gene in tumor cells. Trastuzumab administered as adjuvant treatment improves recurrence-free survival by 7% and overall survival by 3%. On the other hand, the same drug combined with chemotherapy in patients with disseminated breast cancer increases objective response rate, improves progression-free survival and overall survival as compared with chemotherapy alone. As estimated, only about 50% of HER2-positive patients obtained a clinical benefit following trastuzumab-based palliative treatment. There are several theories explaining the phenomenon of primary and secondary resistance to antibody-treatment. Patients previously undergoing with anthracycline- and taxoid-based chemotherapy, who experience recurrence or progression after trastuzumab, may benefit from administration of lapatinib, a HER1/HER2-associated small-molecule tyrosine kinase inhibitor, combined with capecitabine. Studies of novel therapeutic strategies in patients with HER2-positive breast cancer are underway, testing both new anti-HER2 antibodies (T-DM1, pertuzumab) and other small-molecule tyrosine kinase inhibitors (neratinib).

Keywords: HER2 overexpression, trastuzumab, cardiotoxicity, lapatinib, lapatinib side effects, trastuzumab-DM1, pertuzumab, neratinib