Page 34 - TD-1-2

Tumor Discovery Fact & challenges of immunotherapy in TNBC

and lymph nodes, but it has not yet reached distant organs. specific T-cells when TNBC has a notable frequency of
The 5-year survival rate of patients with stage 3 TNBC is non-synonymous gene mutations, which lead to tumor-
84%. Stage 4 BC indicates that the cancer has metastasized specific neoantigens . These neoantigen-specific T-cell
[16]
(spread to other areas of the body), and patients with stage responses can be amplified by ICIs [17,18] .
4 TNBC have only about a 10% chance of survival [2,3] . This review offers a framework for comprehending the
After all, TNBC is curable when it is diagnosed in the first most recent clinical data relating to immune checkpoint
three stages. The life expectancy and survival rate for stage blockade (ICB) and other new immunotherapy drugs
3 TNBC are constantly improving [4,5] . At present, there for TNBC. Future directions for the development of
are many treatments available for BC, including surgery, immunotherapy in TNBC are also explored, along
chemotherapy, targeted therapy, and radiotherapy, among with the development of immunotherapy biomarkers
which chemotherapy is the primary systemic treatment (Tables 1 and 2).
[6]
for the majority of metastatic TNBC (mTNBC) patients .
However, responses are frequently transient, and patients 2. Immunotherapy in triple-negative breast
have median OS of 12 – 18 months. Moreover, traditional cancer
chemotherapy drugs, including paclitaxel, anthracycline,
and alkylating agents, are likely to cause side effects and 2.1. Triple-negative breast cancer characteristics
systemic toxicity [4,7] . Therefore, the demand for better TNBC accounts for 15 – 25% of all BCs and is widely
therapeutics is increasing. recognized as the worst BC among all the subtypes of
BC, posing a huge threat to patients diagnosed with BC .
[1]
Based on the expression of ER, PR, and HER2, BC
can be classified into four intrinsic subtypes: luminal TNBC can be classified into four robust subtypes based
A, luminal B, HER2+, and TNBC. In most cases, these on their different transcriptomic characteristics: basal-
like (BL), immunomodulatory (IM), mesenchymal stem-
subtypes have specific immunological characteristics, like (MSL), and luminal androgen receptor (LAR) .
[30]
with different expression levels of tumor-infiltrating A large number of studies have indicated that age, sex,
lymphocytes (TILs) . In recent years, researchers have and even race can be risk factors of TNBC. According to
[8]
found that BC is immunogenetic regardless of its subtype. research, BRCA and basal TNBC, as well as apocrine and
Lymphocyte-predominant BCs that have stromal or neuroendocrine TNBC, are more common in younger and
intratumorally lymphocytes make up more than 50 – 60% older women compared to the same age groups in men. It
of the tumor tissue [9,10] . Given that immunotherapy has has been documented that Hispanic and African American
improved survival in other solid tumors, it may also be a women are at a higher risk of TNBC and have a poorer
viable option for TNBC treatment. Immune checkpoint prognosis than other populations. In a case study, there
inhibitors (ICIs), which inhibit immunosuppressive was a 2.5% increased risk of TNBC in 187 TNBC patients
receptors such as programmed cell death 1 (PD-1) and who had taken oral contraceptives for more than a year,
cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) the risk of TNBC was 4.2% for women under the age of
to increase the cytotoxicity and proliferation of tumor- 40, and it was discovered that the risk rose as the duration
infiltrating cells, are the most effective immunotherapy of oral contraceptive use increased . In the United States,
[17]
drugs. ICIs, such as pembrolizumab, nivolumab, TNBC accounts for 12% of BC cases, with 8 – 16% 5-year
[11]
atezolizumab, durvalumab, and avelumab , which are survival rate.
monoclonal antibodies against PD-1, programmed cell
death-ligand 1 (PD-L1), and CTLA-4, have produced long- Other than the four robust subtypes of TNBC, which
lasting responses in a variety of tumor types [12-15] . can be detected at the transcriptomic level, there are
four discrete subtypes: LAR, mesenchymal (MES), basal-
Compared with other subtypes, TNBC is more likely like immune suppressed (BLIS), and basal-like immune
to react to immunotherapy due to a number of factors. activated (BLIA) . LAR represents TNBC tumors
[18]
First off, TNBC contains higher levels of TILs than other with the lowest genomic complexity, with mutations in
BC subtypes, which have been found to be associated with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic
more significant responses to ICIs and a better prognosis subunit alpha (PIK3CA), AKT serine/threonine kinase 1
for TNBC in its early stages . Second, TNBC has (AKT1), neurofibromatosis type 1 (NF1), GATA binding
[16]
significantly different levels of PD-L1 expression on both protein 3 (GATA3), and cadherin-1 (CDH1) [12-15] . The
immune and cancer tissues , making it a direct target for mesenchymal subtype is characterized by lower genomic
[17]
ICIs and correlating with how well those treatments work complexity and activation of PI3K pathway . BLIA
[31]
in treating other malignancies . Third, a better anti-tumor represents the majority of TNBCs with a complex genomic
[4]
immune response has been mounted by neoantigen- profile, having TP53 mutations in more than 90% of cases
Volume 1 Issue 2 (2022) 2 https://doi.org/10.36922/td.v1i2.196