Abstract
Hormone receptor-positive breast cancer is commonly treated with endocrine therapy (ET); however, over time, cancer cells can develop endocrine resistance. This review aims to document combination therapy and sequential therapy in the use of endocrine agents and targeted agents, by conducting two systematic searches using four databases: Cochrane Library, MEDLINE, EMBASE and Web of Science. A total of 26 studies that covered combination therapy were obtained and included for the review. Fourteen were phase III documenting combinations of mechanistic target of rapamycin (mTOR), phosphoinositide-3-kinase (PI3K), vascular endothelial growth factor receptor, human epidermal growth factor receptor 2 and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The remaining studies were of phase II nature that reported combinations involving inhibitors in mTOR, endothelial growth factor receptor, CDK4/6 and TKI. Interesting findings in inhibitor combinations involving CDK4/6, mTOR and PI3K suggest clinical activity that can overcome endocrine resistance. On the other hand, there were 0 studies that covered sequential therapy. Overall findings showed that combination therapy improved treatment efficacy over monotherapy in postmenopausal patients with hormone receptor-positive advanced breast cancer. Inevitably, the benefits are accompanied with increased toxicity. To optimise ET, further research into combinations and effective patient selection will need to be defined. Additionally, this review warrants future studies to explore sequential therapy.
Highlights
Endocrine therapy (ET) is often used as first-line treatment in patients with hormone receptor-positive (HR+) breast cancer and preferred to chemotherapy when there are no signs of visceral crisis (Reinert & Barrios 2015)
ET improves progression-free survival (PFS), time to progression (TTP), objective response rate (ORR) and clinical benefit response (CBR), while possessing a favourable toxicity profile when compared to chemotherapy
The therapeutic action of ET is slower than chemotherapy, the duration of response in ET is more sustainable with longer-term survival benefits (Cheung 2007)
Summary
Endocrine therapy (ET) is often used as first-line treatment in patients with hormone receptor-positive (HR+) breast cancer and preferred to chemotherapy when there are no signs of visceral crisis (Reinert & Barrios 2015). ET improves progression-free survival (PFS), time to progression (TTP), objective response rate (ORR) and clinical benefit response (CBR), while possessing a favourable toxicity profile when compared to chemotherapy. The therapeutic action of ET is slower than chemotherapy, the duration of response in ET is more sustainable with longer-term survival benefits (Cheung 2007). Investigations in modalities of ET agents have been thorough and produced a wide range of ET options for patients to use
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