Abstract
Breast cancer (BC) is the most common malignancy among females. Chemotherapy drugs remain the cornerstone of treatment of BC and undergo significant shifts over the past 100 years. The advent of immunotherapy presents promising opportunities and constitutes a significant complementary to existing therapeutic strategies for BC. Chemotherapy as a cytotoxic treatment that targets proliferation malignant cells has recently been shown as an effective immune-stimulus in multiple ways. Chemotherapeutic drugs can cause the release of damage-associated molecular patterns (DAMPs) from dying tumor cells, which result in long-lasting antitumor immunity by the key process of immunogenic cell death (ICD). Furthermore, Off-target effects of chemotherapy on immune cell subsets mainly involve activation of immune effector cells including natural killer (NK) cells, dendritic cells (DCs), and cytotoxic T cells, and depletion of immunosuppressive cells including Treg cells, M2 macrophages and myeloid-derived suppressor cells (MDSCs). Current mini-review summarized recent large clinical trials regarding the combination of chemotherapy and immunotherapy in BC and addressed the molecular mechanisms of immunostimulatory properties of chemotherapy in BC. The purpose of our work was to explore the immune-stimulating effects of chemotherapy at the molecular level based on the evidence from clinical trials, which might be a rationale for combinations of chemotherapy and immunotherapy in BC.
Highlights
Breast cancer (BC), a highly heterogeneous disease, is the most common cancer among women [1]
In 2001, a National Institute of Health consensus panel concluded that owing to a clear survival benefit by adjuvant polychemotherapy, it should be recommended to the majority of women with localized BC regardless of lymph node, menopausal, or hormone receptor status [10]
Results in the ITT population were 7·5 and 5·6 months. These findings suggested a role for the combination of pembrolizumab and chemotherapy for the first-line treatment of metastatic triple negative breast cancer (TNBC) [20]
Summary
Breast cancer (BC), a highly heterogeneous disease, is the most common cancer among women [1]. Conclusions from IMpassion131 contrasted with results from the KEYNOTE-355 trial (we will further elaborate below) that evaluated a more extensively chemotherapy backbones (including both paclitaxel and nab-paclitaxel, as well as gemcitabine/carboplatin) with a different immunotherapy agent, pembrolizumab [15] Both IMpassion130 and IMpassion131 excluded patients with early relapse (disease progression within 12 months of chemotherapy for early breast cancer), IMpassion132 (NCT03371017) is one of the first trials prospectively focusing on the early relapsing TNBC population. KEYNOTE-355 (NCT02819518), compared pembrolizumab plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) with placebo plus chemotherapy, showed a significant and clinically meaningful improvement in PFS among patients with locally recurrent inoperable or metastatic TNBC with combined positive score(CPS)of 10 or more. The upregulation of MHCrelated molecules could remodel the immunopeptidome of cancer cells after chemotherapy, and enhancing their antigenicity
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