Abstract
In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including the expression of hormone receptors (estrogen receptor and/or progesterone receptor) and/or HER2. Primary breast cancer treatments can include surgery, radiation therapy, systemic chemotherapy, endocrine therapy, and/or targeted therapy. Endocrine therapy has been shown to be effective in hormone receptor-positive breast cancers and is a common choice for adjuvant therapy. However, due to the aggressive nature of triple-negative breast cancer, targeted therapy is becoming a noteworthy area of research in the search for non-endocrine-targets in breast cancer. In addition to HER2-targeted therapy, other emerging therapies include immunotherapy and targeted therapy against critical checkpoints and/or pathways in cell growth. This review summarizes novel targeted breast cancer treatments and explores the possible implications of combination therapy.
Highlights
New and Emerging TargetedBreast cancer (BC) is one of the most commonly diagnosed cancers in women in the United States
These findings suggest a possible promising direction for phosphatase and tensin homolog (PTEN) upregulation in future cancer therapeutics
The potential of tyrosine kinase inhibitors (TKIs) to cross the blood–brain barrier opens the door to the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer with central nervous system (CNS) metastasis, and the increasing implication of TKIs in the treatment and combination treatment of metastatic breast cancer make for a promising outlook for TKI research in the future
Summary
Breast cancer (BC) is one of the most commonly diagnosed cancers in women in the United States. Due to the heterogeneity of breast cancer, it remains imminent that therapies and treatments become increasingly targeted to address the subtype, stage, and grade of breast cancer [8]. Personalized therapy for hormone receptor-positive breast cancer has been well established, including selective estrogen receptor modulators and degraders (SERMs and SERDs), aromatase inhibitors (AI), and endocrine therapy. More recent investigation has revealed improved therapies targeting other subtypes such as triple-negative breast cancer (TNBC) and HER2-positive BC [8]. New emerging technologies are on the horizon for the treatment of breast cancer, including immuno-oncolytic virus drugs, histone deacetylase inhibitors, and novel combination therapies [9–11]. HR: hormone receptor; ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor 2; TNBC: triple-negative breast cancer; mTOR: mammalian target of rapamycin; PI3K: phosphoinositide. 3-kinase; TKI: tyrosine kinase inhibitor; PARP: poly-ADP-ribose polymerase; CDK: cyclin-dependent kinase; LKB1: liver kinase B1; AMPK: adenosine monophosphate-activated protein kinase; T-DM1: trastuzumab emtansine; T-DXd: trastuzumab deruxtecan; IMMU-132: sacituzumab govitecan; PTEN: phosphatase and tensin homolog; PIK3CA: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene; tx: treatment; hx: history; gBRCA: germline breast cancer-associated protein; BC: breast cancer; AI: aromatase inhibitor; GM-CSF: granulocyte-macrophage colony-stimulating factor
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