151P - Intratumor heterogeneity of ER status is a feature of interaction between mammary carcinoma cells and microenvironment

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Basic Science
Breast Cancer
Presenter Iryna Boichuk
Authors I. Boichuk1, D. Burlaka2
  • 1Department Of Cancer Experimental Therapeutics, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, 03022 - Kyiv/UA
  • 2Biotechnical Problems Of Diagnostic, Institute Problems of Cryobiology and Cryomedicine of the National Academy of Sciences (IPCC), 03022 - Kiev/UA

Abstract

The growth and survival of mammary carcinoma cells often depend on their estrogen sensitivity proving a rationale for targeted therapy. The relationship between tumor growth and changing hormonal environment is demonstrated both in experiment and in clinical setting (age-related difference in breast cancer prognosis, changing estrogen and progesterone receptor patterns in breast carcinoma during the menstrual cycle and menopause, etc.). The aim of this study was to analyze the effects of the changing hormonal environment in the setting of the oestrus cycles on tumor growth and levels of estrogen receptors (ER) in murine mammary tumors.

Methods

The dextran-coated charcoal radioactive ligand-binding ER assay method was used followed by Scatchard analysis.

Results

The increment of tumor volume in mouse with mammary carcinoma is not a linear one but followed the pattern of changing hormonal levels within 4-day oestrus cycle in a wave-shaped manner. Upon the plateau of tumor growth, receptors are lost in half of cells. Thus, the population becomes heterogeneous in ER content. The widely accepted hypothesis that the interaction of estrogen with cellular ER determines the hormone dependency of mammary tumors should now be challenged on the basis of the following observations: a) tumors arising in experimental animals with permanent high estrogen levels are receptor-positive and that with low estrogen levels are receptor-negative; b) tumors regrowing after complete or partial regression as a result of endocrine ablation or hormone administration are considered to be environment dependent rather than autonomous or hormone dependent; c) mammary tumors growing in the setting of cyclically changing hormonal level become heterogeneous.

Conclusion

Tumor cells are highly sensitive to alterations in hormonal background. The adaptation to the altered microenvironment could promote metastases, tumor heterogeneity, and, oddly enough, transform the tumors into a nonmalignant state.

Disclosure

All authors have declared no conflicts of interest.