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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.
Highlights
In 2019, the Canadian Cancer Statistics Advisory Committee estimated that 29,300 Canadians are diagnosed with lung cancer annually and 21,000 die from it [1]
The only patients with a prospect of cure are those with early stage non-small cell lung cancer (NSCLC) who are amenable to surgical resection with curative intent [2]
Our objective was to quantify the effect of the COVID-19 pandemic on surgical lung cancer care as perceived by practicing thoracic surgeons during the first wave of the pandemic in Canada
Summary
In 2019, the Canadian Cancer Statistics Advisory Committee estimated that 29,300 Canadians are diagnosed with lung cancer annually and 21,000 die from it [1]. In the era of COVID-19, routine lung cancer physiologic and staging assessments are unique in that they are droplet producing and aerosolizing procedures. These include pulmonary function testing (PFT), endobronchial ultrasound, and bronchoscopy [4]. Routine lung cancer physiologic and staging assessments are unique in that they are droplet producing and aerosolizing procedures. Our objective was to quantify the effect of the COVID-19 pandemic on surgical lung cancer care as perceived by practicing thoracic surgeons during the first wave of the pandemic in Canada. Assessing the extent and effects of newly present barriers to standard lung cancer care is essential in forming appropriate mitigation strategies and planning for future pandemic waves
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