Heterogeneity of breast cancer: The importance of interaction between different tumor cell populations

Introduction: Breast cancer is the most common cancer and the second leading cause of cancer-related death in women worldwide. Despite the early detection of breast cancer and increasing knowledge of its biology and chemo-resistance, metastatic breast cancer is largely incurable disease. We provide a review of the intertumor and intratumor heterogeneity, explain the differences between triple-negative breast cancer subtypes. Also, we describe the interaction of breast tumor cells with their microenvironment cells and explain how this interaction contributes to the tumor progression, metastasis formation and resistance to the treatment. Discussion: One of the main causes that complicate the treatment is tumor heterogeneity. It is observed among patients (intertumor heterogeneity) and in each individual tumor (intratumor heterogeneity). In the case of intratumor heterogeneity, the tumor consists of different phenotypical cell populations. During breast cancer subtype identification, a small piece of solid tumor tissue does not necessarily represent all the tumor composition. Breast tumor cell phenotypical differences may appear due to cell localization in different tumor sites, unique response to the treatment, cell interaction with tumor microenvironment or tumor cell interaction with each other. This heterogeneity may lead to breast cancer aggressiveness and challenging treatment. Conclusion: Understanding the molecular and cellular mechanisms of tumor heterogeneity that are relevant to the development of treatment resistance is a major area of research. Identification of differences between populations and their response to anticancer drugs would help to predict the potential resistance to chemotherapy and thus would help to select the most suitable anticancer treatment.