HER2-позитивный рак молочной железы принято выделять в особый морфологический подтип, для которого характерны плохой прогноз и низкая чувствительность к химиотерапии. Появление первого препарата направленного действия против HER2-рецепторов – трастузумаба позволило значительно улучшить результаты лечения больных HER2-позитивным раком молочной железы. Однако у части пациентов развивается резистентность к трастузумабу, а часть – исходно не чувствительны к данному препарату. Разработаны практические подходы, которые помогают добиться эффекта в ситуации рефрактерности или резистентности к трастузумабу. В частности, в настоящей статье описаны 2 случая успешного применения малой молекулы ингибитора HER2 и EGFR – лапатиниба в различных комбинациях.
HER2-positive breast cancer is a special type of tumor with overexpression of HER2-receptors or HER2 gene amplification. HER2-positive breast cancers tend to be more aggressive than other types of breast cancer. They're also less responsive to hormone treatment and chemotherapy. However, treatments that specifically target HER2 are very effective. Trastusumab is the first targeted agent against HER2-receptors which has improved the treatment results in HER2-positive breast cancer. However, in the routine clinical practice we faced developed resistance or primary insensitivity to trastusumab. Different approaches have been developed for overcoming resistance to trastusumab. In this article we have described two clinical cases of high effective usage of the small molecule, HER2 and EGFR inhibitor – lapatinib in different combinations.
Key words: HER2-positive breast cancer, case report, lapatinib.
1. Slamon DJ et al. Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 1987; 235: 177–82.
2. Romond EH et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353: 1673–84.
3. Tripathy D, Slamon DJ et al. Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol 2004; 22: 1063–70.
4. Montemurro F, Donadio M et al. Outcome of patients with HER2-positive advanced breast cancer progressing during trastuzumab-based therapy. Oncolog 2006; 11: 318–24.
5. http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
6. Spector NL, Xia W et al. Study of the biological effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. J Clin Oncol 2005; 23: 2502–12.
7. Jackisch C. HER2-positive metastatic breast cancer: optimizing trastuzumab-based therapy. Oncolog 2006; 11 (Suppl. 1): 34–41.
8. von Minckwitz G, du Bois A, Schmidt M et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German breast group 26/breast international group 03–05 study. J Clin Oncol 2009; 27: 1999–2006.
9. Gomez HL. A randomized open-label, phase II study of lapatinib/capecitabine, lapatinib/vinorelbine, or lapatinib/gemcitabine in patients (pts) with ErbB2-amplified metastatic breast cancer (MBC) progressing after taxane treatment GLICO-0801. ASCO Ann Meeting. J Clin Oncol 2010; 28 (Suppl.): 15. Abstr. TPS120.
1 ФГБУ Московский научно-исследовательский онкологический институт им. П.А.Герцена Минздравсоцразвития РФ
2 Медицинский радиологический научный центр РАМН, Обнинск