Challenges in the management of advanced, ER-positive, HER2-negative breast cancer

Abstract

Hormone-receptor-positive breast cancer accounts for the majority-up to 80%-of all breast cancers. The evolution of breast cancer from early stage to the metastatic setting leads to increased heterogeneity, the occurrence of new mutations, and the development of treatment resistance representing a great challenge for management decisions. Unfortunately, little data exist to offer guidance in this context, and a reliance on traditional clinical parameters remains when deciding on optimal treatment. In advanced-stage oestrogen receptor-positive (ER+) disease, ongoing issues include the choice between endocrine therapy and chemotherapy, the appropriate sequence of treatment agents, and the incorporation of biological agents, such as everolimus, into the treatment armamentarium. In metastatic disease, repeated biopsies can help to reassess the receptor or genetic mutational status; however, the evidence to support this approach is limited. In this Review, we examine the current evidence that can guide treatment decisions in patients with advanced-stage ER+ breast cancer, discuss how to tackle these therapeutic challenges and provide suggestions for the optimal management of this patient population.

Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review

“…Breast cancer is categorized into three subtypes according to estrogen receptor (ER), progesterone receptor (PR) and HER2 status: hormone receptor (HR)‐positive, HER2‐positive and triple negative subtypes . Of these, HR‐positive breast cancers constitute approximately 60%–70% . Endocrine therapy is considered to be the mainstay therapy for HR‐positive breast cancer .…”

Breast tumor stroma: A driving force in the development of resistance to therapies

“…Resistance to chemotherapy is still a problematic issue and challenging factor in the breast cancer treatment. [1] As a second common cause of cancer death in women, the importance of focusing on the underlying mechanisms of multidrug resistance (MDR) in breast cancer has been increased. [2] Therefore, in the last decade, considerable attention has been dedicated to the role played by multifactorial MDR.…”

Fluorescence Analysis of Vitamin D Receptor Status of Circulating Tumor Cells (CTCS) in Breast Cancer: From Cell Models to Metastatic Patients

“…However, as BC is an extremely heterogeneous disease, resistance to treatment is a major clinical challenge for current BC management [1]. Therefore, the development of more specific biomarkers and recognition of new therapeutic targets would really contribute to solving the problems of therapy resistance and metastasis [2,3,4]. In recent years, an increasing number of clinical studies have suggested that an optimal vitamin D status has a protective effect against BC development and that high Vitamin D receptor (VDR) expression in breast tumors is associated with a better survival rate [5,6,7,8].…”