Influence of tumor microenvironment on the different breast cancer subtypes and applied therapies.

Despite the significant improvements made in breast cancer therapy during the last decades, this disease still has increasing incidence and mortality rates. Different targets involved in general processes, like cell proliferation and survival, have become alternative therapeutic options for this disease, with some of them already used in clinic, like the CDK4/6 inhibitors for luminal A tumors treatment. Nevertheless, there is a demand for novel therapeutic strategies focused not only on tumor cells, but also on their microenvironment. Tumor microenvironment (TME) is a very complex and dynamic system that, more than surrounding and supporting tumor cells, actively participates in tumor development and progression. During the last decades, it has become clear that the cellular and acellular components of TME differ between the various breast cancer subtypes and shape the differences regarding their severity and prognosis. The pivotal role of the TME in controlling tumor growth and influencing responses to therapy represents a potential source for novel targets and therapeutic strategies. In this review, we present a description of the multiple therapeutic options used for different breast cancer subtypes, as well as the influence that the TME may exert on the development of the disease and on the response to the distinct therapies, which in some cases may explain their failure by the occurrence of relapses and resistance. Furthermore, the ongoing studies focused on the use of TME components for developing potential cancer treatments are described.

Estrogen receptor-positive (ER+) breast cancer treatment: Are multi-target compounds the next promising approach?

Endocrine therapy is currently the main therapeutic approach for estrogen receptor-positive (ER+) breast cancer, the most frequent subtype of breast cancer in women worldwide. For this subtype of tumors, the current clinical treatment includes aromatase inhibitors (AIs) and anti-estrogenic compounds, such as Tamoxifen and Fulvestrant, being AIs the first-line treatment option for post-menopausal women. Moreover, the recent guidelines also suggest the use of these compounds by pre-menopausal women after suppressing ovaries function. However, besides its therapeutic efficacy, the prolonged use of this type of therapies may lead to the development of several adverse effects, as well as, endocrine resistance, limiting the effectiveness of such treatments. In order to surpass this issues and clinical concerns, during the last years, several studies have been suggesting alternative therapeutic approaches, considering the function of aromatase, ERα and ERß. Here, we review the structural and functional features of these three targets and their importance in ER+ breast cancer treatment, as well as, the current treatment strategies used in clinic, emphasizing the importance of the development of multi-target compounds able to simultaneously modulate these key targets, as a novel and promising therapeutic strategy for this type of cancer.