Abstract
Introduction:
It is generally accepted that trastuzumab has only effective in HER2+ breast cancer patients who have HER2 gene amplification or HER2 over expression. On the other hand, trastuzumab resistance is a problem in HER2+ patients. Our aim is to investigate the effects of trastuzumab, paclitaxel and carboplatin on cancer stem cells which is isolated from primary breast cancer cultures.
Methods:
Tumor tissue was obtained in the routine surgery of a breast cancer patient who was HER2+ by immunohistochemistry. Primary breast cancer culture were established. CD44+CD24- and ALDH+ breast cancer stem cells were sorted by flowcytometry from these culture. HER2 receptor status of the sorted cells was also determined by flowcytometry. HER2+ and HER2- breast cancer stem cells were treated with trastuzumab, paclitaxel and carboplatin, and combination of these drugs by checker board microplate method for 96 h. For all of these breast cancer stem cell subgroups, the responses to the drugs were determined.
Results:
Breast cancer stem cells were isolated from a HER2+ breast cancer patient. The cell sorting analysis results demonstrates that 43% of the population is CD44+CD24- and 22% of the population is ALDH+. CD44+CD24- breast cancer stem cell subpopulation contains 84% HER2+ and 16% HER2- cells. Carboplatin has the highest antiproliferative effect on cancer stem cells among the three drugs which means carboplatin application resulted in the lowest IC50 values in all subgroups (IC50: 0.26 μM- 0.41 μM). HER2- cancer stem cells are more resistant to the drugs (1.5- 2 fold resistance) than HER2+ subcultures. Although combination of drugs exerted synergistic effect on the subcultures, ‘breast cancer stem cells’ were found to be more resistant to the combination therapy by exhibiting higher proliferation in drug combinations.
Conclusions:
HER2- cancer stem cells may be one of reason for trastuzumab resistance in HER2+ breast cancer patients. The result of this experimental study may be used to suggest new treatment strategies in HER2+ breast cancer patients.
Citation Format: Mehmet Artac, Gozde Kayadibi, Ayca Ceylan, Meltem Demirel Kars, Hasibe Artac, Murat Cakır, Cem Boruban, Ahmet Tekin, Lema Tavlı, Adil Kartal. The effects of trastuzumab, paclitaxel, and carboplatin on HER2-positive cancer stem cells that are isolated from primary breast cancer cultures: a preliminary report. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 718. doi:10.1158/1538-7445.AM2015-718
- ©2015 American Association for Cancer Research.
Volume 75, Issue 15 Supplement
