Journal of the National Cancer Institute
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J. Natl. Cancer Inst. · Oct 2015
ReviewEnhancing Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer: Cotargeting Signaling Pathways.
Overcoming primary or secondary endocrine resistance in breast cancer remains critical to further enhancing the benefit of existing therapies such as tamoxifen or an aromatase inhibitor (AI). Much progress has been made in understanding the molecular biology associated with secondary endocrine resistance. ⋯ Numerous other therapeutics are being evaluated in combination with endocrine therapies based on supportive preclinical evidence, including inhibitors of PI3K, Akt, HDAC, Src, IGFR-1, and FGFR. Appropriate clinical trial design and patient selection based on prior therapy exposure, together with predictive biomarkers derived through real-time molecular profiling, are needed to enrich future trials and maximize any additional benefit that cotargeting may bring to current endocrine therapies for estrogen receptor-positive breast cancer.