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Abstract
Simple SummaryMany persons diagnosed with breast cancer are treated with endocrine therapy and will experience the side effects of endocrine therapy. Cognitive adverse effects of endocrine therapy are increasingly being recognised, and can significantly affect quality of life, adherence and treatment outcome. This review aims to discuss the nature of cognitive dysfunction associated with endocrine therapy, the mechanisms underpinning its development, and evidence-based management strategies.Endocrine therapy forms the backbone of systemic therapy for the majority of persons with early and late-stage breast cancer. However, the side effects can negatively affect quality of life, and impact treatment adherence and overall oncological outcomes. Adverse effects on cognition are common, underreported and challenging to manage. We aim to describe the nature, incidence, risk factors and underlying mechanisms of endocrine therapy-induced cognitive dysfunction. We conducted a comprehensive literature review of the studies reporting on cognitive dysfunction associated with endocrine therapies for breast cancer. We also summarise prevention and treatment strategies, and ongoing research. Given that patients are taking endocrine therapies for longer durations than ever before, it is essential that these side effects are managed pro-actively within a multi-disciplinary team in order to promote adherence to endocrine therapy and improve patients’ quality of life.
Highlights
Worldwide, breast cancer is the most common cancer diagnosed in women, with a lifetime incidence of 5–20%, and it is the leading cause of cancer-related death [1,2]
In advanced-stage breast cancer, combining endocrine therapy with molecular therapies targeting intracellular pathways, such as cyclindependent kinase (CDK) 4/6 inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors and mammalian target of rapamycin inhibitors, have been highly efficacious when used in combination with endocrine therapy as a backbone [9,10]
CDK 4/6 inhibitors combined with endocrine therapy are standard first line treatment for metastatic hormone receptor positive, HER2 negative breast cancer based on significant improvements in progression free survival and overall survival [11,12,13]
Summary
Breast cancer is the most common cancer diagnosed in women, with a lifetime incidence of 5–20%, and it is the leading cause of cancer-related death [1,2]. Endocrine therapy forms the backbone of treatment of ER+ breast cancer, and includes selective oestrogen receptor modulators (e.g., tamoxifen), selective oestrogen receptor degraders (e.g., fulvestrant), aromatase inhibitors (e.g., letrozole, anastrazole, exemestane) and ovarian function suppression (e.g., goserelin). While each of these treatments has a different mechanism of action, menopausal symptoms and cognitive side effects have been reported with most of these agents. Many advances have contributed to declines in mortality attributable to breast cancer, and survival is predicted to increase further in the coming years [4]. CDK 4/6 inhibitors combined with endocrine therapy are standard first line treatment for metastatic hormone receptor positive, HER2 negative breast cancer based on significant improvements in progression free survival and overall survival [11,12,13]
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