ABSTRACT
Endocrine therapy, a major modality in the treatment of hormone receptor (hr)-positive breast cancer (bca), has improved outcomes in metastatic and nonmetastatic disease. However, a limiting factor to the use of endocrine therapy in bca is resistance resulting from the development of escape pathways that promote the survival of cancer cells despite estrogen receptor (er)-targeted therapy. The resistance pathways involve extensive cross-talk between er and receptor tyrosine kinase growth factors [epidermal growth factor receptor, human epidermal growth factor receptor 2 (her2), and insulin-like growth factor 1 receptor] and their downstream signalling pathways-most notably pi3k/akt/mtor and mapk. In some cases, resistance develops as a result of genetic or epigenetic alterations in various components of the signalling pathways, such as overexpression of her2 and erα co-activators, aberrant expression of cell-cycle regulators, and PIK3CA mutations. By combining endocrine therapy with various molecularly targeted agents and signal transduction inhibitors, some success has been achieved in overcoming and modulating endocrine resistance in hr-positive bca. Established strategies include selective er downregulators, anti-her2 agents, mtor (mechanistic target of rapamycin) inhibitors, and inhibitors of cyclin-dependent kinases 4 and 6. Inhibitors of pi3ka are not currently a treatment option for women with hr-positive bca outside the context of clinical trial. Ongoing clinical trials are exploring more agents that could be combined with endocrine therapy, and biomarkers that would help to guide decision-making and maximize clinical efficacy. In this review article, we address current treatment strategies for endocrine resistance, and we highlight future therapeutic targets in the endocrine pathway of bca.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Drug Resistance, Neoplasm/drug effects , Molecular Targeted Therapy/methods , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Female , Humans , Protein Kinase Inhibitors/therapeutic use , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolismABSTRACT
The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: â Follow-up and survivorship of patients with resected colorectal cancerâ Indications for liver metastasectomyâ Treatment of oligometastases by stereotactic body radiation therapyâ Treatment of borderline resectable and unresectable pancreatic cancerâ Transarterial chemoembolization in hepatocellular carcinomaâ Infectious complications of antineoplastic agents.
