Abstract
Triple negative breast cancer (TNBC) is an aggressive breast cancer with historically poor outcomes, primarily due to the lack of effective targeted therapies. The tumor molecular heterogeneity of TNBC has been well recognized, yet molecular subtype driven therapy remains lacking. While neoadjuvant anthracycline and taxane-based chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is debatable. The addition of carboplatin to anthracycline, cyclophosphamide, and taxane (ACT) regimen is associated with improved complete pathologic response (pCR). Immune checkpoint inhibitor (ICI) combinations significantly increase pCR in TNBC. Increased tumor infiltrating lymphocyte (TILs) or the presence of DNA repair deficiency (DRD) mutation is associated with increased pCR. Other targets, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and Phosphatidylinositol-3-kinase/Protein Kinase B/mammalian target of rapamycin (PI3K-AKT-mTOR) pathway inhibitors, are being evaluated in the neoadjuvant setting. This review examines recent progress in neoadjuvant therapy of TNBC, including platinum, ICI, PARPi, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) pathway targeted therapies, and novel tumor microenvironment (TME) targeted therapy, in addition to biomarkers for the prediction of pCR.
Highlights
Triple negative breast cancer (TNBC) accounts for 15% of all breast cancer and it is characterized by the lack of expression of estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor-2 (HER-2), earlier recurrence, tendency of visceral metastasis, and worse overall survival [1,2,3]
This review examines recent progress in neoadjuvant therapy of TNBC, including platinum, Immune checkpoint inhibitor (ICI), poly-ADP-ribosyl polymerase inhibitors (PARPi), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) pathway targeted therapies, and novel tumor microenvironment (TME) targeted therapy, in addition to biomarkers for the prediction of Pathological complete response (pCR)
Many promising targeted therapies and approaches that are discussed in this review may lead to a paradigm shift of neoadjuvant therapies for early stage TNBC
Summary
Triple negative breast cancer (TNBC) accounts for 15% of all breast cancer and it is characterized by the lack of expression of estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor-2 (HER-2), earlier recurrence, tendency of visceral metastasis, and worse overall survival [1,2,3]. Tumor heterogeneity of TNBC is well recognized [12,13,14], yet molecular subtype driven therapy has not become a routine clinical practice, largely due to the lack of effective targeted therapies. (PIK3CA) pathway inhibitors and androgen receptor (AR) targeted therapies, may be applicable for certain molecular subtypes of TNBCs. Novel approaches in conducting neoadjuvant clinical trials, such as I-SPY 2 and ARTEMIS, may accelerate the progress to bring effective targeted therapies to the neoadjuvant setting [18,19,20,21]. We will summarize recent neoadjuvant trials focusing on the following perspectives: (a) chemotherapy optimization with the addition of carboplatin; (b) the addition of ICI to chemotherapy backbones; (c) clinical trial design by the evaluation of novel targeted agents such as I-SPY 2; (d) biomarker driven identification of clinically relevant patient subgroups to enable a more precise treatment approach (ARTEMIS).
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