How to Predict Metastasis in Luminal Breast Cancer? Current Solutions and Future Prospects

Abstract

Breast cancer metastasis is the main cause of breast cancer mortality. Luminal breast cancer represents the majority of breast cancer cases and, despite relatively good prognosis, its heterogeneity creates problems with a proper stratification of patients and correct identification of the group with a high risk of metastatic relapse. Current prognostic tools are based on the analysis of the primary tumor and, despite their undisputed power of prediction, they might be insufficient to foresee the relapse in an accurate and precise manner, especially if the relapse occurs after a long period of dormancy, which is very common in luminal breast cancer. New approaches tend to rely on body fluid analyses, which have the advantage of being non-invasive and versatile and may be repeated and used for monitoring the disease in the long run. In this review we describe the current, newly-developed, and only-just-discovered methods which are or may become useful in the assessment of the probability of the relapse.

Keywords: ER-positive; breast cancer metastasis; circulating tumor markers; dormancy; hormonal crosstalk; multigene tests.

Figure 1

Estrogen receptor (ER) chromatin binding is re-programed in a presence of progesterone-bound progesterone receptor (PR). (A) In the presence of estradiol, ER binds to estrogen-responsive elements (ERE) in a proximal region of the promoter, but in a presence of both hormones, estradiol and progesterone, hormone-bound receptors form a complex which binds to more distal progesterone-responsive elements (PRE), re-programing the transcription profile. (B) The progesterone/estradiol ratio changes depending on the phase of menstrual cycle, assuming the lowest numbers in post-menopausal women (approximate ratio based on a data from The Global Library of Women’s Medicine). The ratio may influence the transcription profile due to a regulation described above.

Figure 2

Metastasis-associated events and the methods of their detection in breast cancer patients.