Abstract
Breast Cancer (BC) is the second most frequent cause of cancer death among women worldwide and, although there have been significant advances in BC therapies, a significant percentage of patients develop metastasis and disease recurrence. Since BC was demonstrated to be an immunogenic tumor, immunotherapy has broken through as a significant therapy strategy against BC. Over the years, immunotherapy has improved the survival rate of HER2+ BC patients due to the approval of some monoclonal antibodies (mAbs) such as Trastuzumab, Pertuzumab and, recently, Margetuximab, along with the antibody-drug conjugates (ADC) Trastuzumab-Emtansine (T-DM1) and Trastuzumab Deruxtecan. Immune checkpoint inhibitors (ICI) showed promising efficacy in triple-negative breast cancer (TNBC) treatment, namely Atezolizumab and Pembrolizumab. Despite the success of immunotherapy, some patients do not respond to immunotherapy or those who respond to the treatment relapse or progress. The main causes of these adverse events are the complex, intrinsic or extrinsic resistance mechanisms. In this review, we address the different immunotherapy approaches approved for BC and some of the mechanisms responsible for resistance to immunotherapy.
Highlights
Breast cancer (BC) is the second leading cause of cancer-related deaths among women worldwide and one in three women have a risk of developing BC in their lifetime, makingBC the leading cause of cancer in the world [1,2]
The IMpassion130 clinical trial contributed to the approval of the atezolizumab with nab-paclitaxel for the treatment of patients with locally advanced or metastatic Triple Negative Breast Cancer (TNBC), whose tumors are positive for protein-Ligand 1 (PD-L1) expression (≥1%) as observed in Table 1 [23,41,73]
An emerging predictive biomarker is the tumor mutational burden (TMB), which is defined as the total number of coding and somatic mutations accumulated in tumor cells that are responsible for the emergence of the tumor-specific-antigens [80]
Summary
Breast cancer (BC) is the second leading cause of cancer-related deaths among women worldwide and one in three women have a risk of developing BC in their lifetime, making. HER2+ BC is an aggressive and fast-growing subtype representing 20% of BC cases [3,7] These tumors are characterized by the HER2/ERBB2 oncogene amplification/overexpression, which causes a higher expression of HER2 and is associated with more invasiveness and recurrence [10,11]. Breast carcinomas that do not express ER, PR and HER2 are classified as basal or triplenegative breast cancer (TNBC) [1] This subtype accounts for approximately 10–20% of all BC and represents a high-risk group associated with increased rates of relapse, recurrence and mortality [7,13,14]. The main cause of its increased aggressiveness and the worse clinical outcomes with TNBC is associated with a highly heterogeneous tumor, which does not have a specific therapeutic target [13,14].
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