Changing Treatment Paradigms in Metastatic Breast Cancer

Abstract

Advances in understanding tumor biology, particularly signaling pathways, have led to the development and approval of many novel agents and have changed the landscape of therapy for patients with metastatic breast cancer. This review highlights some of the recent successes and failures in breast cancer drug development, including strategies to overcome endocrine and human epidermal growth factor 2-neu (HER2) resistance, targeting triple-negative breast cancers (which do not express the HER2, estrogen, and progesterone receptors) through novel receptors, harnessing the immune system, and new ways of targeting angiogenesis. For patients with metastatic breast cancer, expanding therapeutic options through clinical trial participation is a crucial part of modern oncology practice. As we continue to learn how to use targeted therapies in the context of genomic medicine, analysis of the tumor in real-time may become increasingly important, giving researchers the information needed to start combining therapies in a biologically informed manner.

miR‑21 is involved in transforming growth factor β1‑induced chemoresistance and invasion by targeting PTEN in breast cancer

“…In recent years, advanced developments in treatment options have been proposed for patients with breast cancer, including neoadjuvant chemotherapy, hormone therapy and targeted therapy (2). However, a number of patients exhibited poor survival due to chemoresistance and metastasis (3).…”

GSK-3 inhibition overcomes chemoresistance in human breast cancer

“…Despite enormous advances in early diagnosis and surgical treatment of breast cancer, as well as improvements in neoadjuvant and adjuvant therapy, approximately 30% of patients with breast cancer will develop incurable metastatic disease [2]. Treatment with conventional chemotherapeutic drugs has had little impact on metastatic disease progression.…”

“…Treatment with conventional chemotherapeutic drugs has had little impact on metastatic disease progression. Metastatic breast cancer remains an incurable disease with median survival times ranging from one to four years depending on the subtype [2,3], and thus represents a significant unmet medical need. The identification of new targeted therapeutic agents is urgently needed.…”

The Role of micro RNAs in Breast Cancer Metastasis: Preclinical Validation and Potential Therapeutic Targets

“…In recent years there have been a number of advances in targeted therapies for BC, for example the combination of aromatase inhibitors with everolimus (afinitor) and cyclindependent kinases 4/6 (cdk4/6) inhibitors such as palbociclib (ibrance) in estrogen-receptor-positive (ER + ) tumors, the use of trastuzumab (herceptin), pertuzumab (perjeta) and adotrastuzumab emtansine (kadcyla) in patients with human epidermal growth factor 2 overexpressing (HER2 + ) tumors and the identification of subgroups of BC patients which respond to Platin-based chemotherapy and poly (adenosinediphosphate-ribose polymerase) (PARP) inhibitors (2)). Yet despite these improvements, a high death toll remains and is due to the difficult tractability of metastatic disease, which is only poorly affected by these agents.…”