Emerging treatment strategies for metastatic triple-negative breast cancer

Huppert, Laura A; Gümüşay, Özge; Rugo, Hope S.

doi:10.1177/17588359221086916

Cited by 18 publications

(10 citation statements)

References 110 publications

(120 reference statements)

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“…Combining ICIs with chemotherapy has had more promising activity. Pembrolizumab in combination with chemotherapy has been approved as a first-line treatment for PD-L1+ advanced TNBC [ 6 , 7 , 8 , 9 , 10 ]. ICIs are also being combined with PARP inhibitors and antibody–drug conjugates (ADCs) for evaluation in clinical studies [ 2 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Addiction of Cancer Stem Cells to MUC1-C in Triple-Negative Breast Cancer Progression

Yamashita

Küfe

2022

IJMS

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Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited treatment options. TNBC progression is associated with expansion of cancer stem cells (CSCs). Few insights are available regarding druggable targets that drive the TNBC CSC state. This review summarizes the literature on TNBC CSCs and the compelling evidence that they are addicted to the MUC1-C transmembrane protein. In normal epithelia, MUC1-C is activated by loss of homeostasis and induces reversible wound-healing responses of inflammation and repair. However, in settings of chronic inflammation, MUC1-C promotes carcinogenesis. MUC1-C induces EMT, epigenetic reprogramming and chromatin remodeling in TNBC CSCs, which are dependent on MUC1-C for self-renewal and tumorigenicity. MUC1-C-induced lineage plasticity in TNBC CSCs confers DNA damage resistance and immune evasion by chronic activation of inflammatory pathways and global changes in chromatin architecture. Of therapeutic significance, an antibody generated against the MUC1-C extracellular domain has been advanced in a clinical trial of anti-MUC1-C CAR T cells and in IND-enabling studies for development as an antibody–drug conjugate (ADC). Agents targeting the MUC1-C cytoplasmic domain have also entered the clinic and are undergoing further development as candidates for advancing TNBC treatment. Eliminating TNBC CSCs will be necessary for curing this recalcitrant cancer and MUC1-C represents a promising druggable target for achieving that goal.

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Section: Introductionmentioning

confidence: 99%

Addiction of Cancer Stem Cells to MUC1-C in Triple-Negative Breast Cancer Progression

Yamashita

Küfe

2022

IJMS

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“…Triple-negative breast cancer (TNBC), characterized by the lack of expression of the estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2), accounts for approximately 12-15% of breast cancers diagnosed worldwide (1)(2)(3). Despite extensive studies that have led to a better understanding of its clinical and biological heterogeneity (4)(5)(6), TNBC remains the most aggressive breast cancer subtype, owing to its high visceral metastatic potential, especially to the lungs and brain (7): The median overall survival (OS) is 10-13 months in the metastatic setting (1).…”

Section: Introductionmentioning

confidence: 99%

Sacituzumab govitecan and radiotherapy in metastatic, triple-negative, and BRCA-mutant breast cancer patient with active brain metastases: A case report

et al. 2023

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BackgroundTriple-negative breast cancer (TNBC) is an aggressive cancer subtype, owing to its high metastatic potential: Patients who develop brain metastases (BMs) have a poor prognosis due to the lack of effective systemic treatments. Surgery and radiation therapy are valid options, while pharmacotherapy still relies on systemic chemotherapy, which has limited efficacy. Among the new treatment strategies available, the antibody-drug conjugate (ADC) sacituzumab govitecan has shown an encouraging activity in metastatic TNBC, even in the presence of BMs.Case presentationA 59-year-old woman was diagnosed with early TNBC and underwent surgery and subsequent adjuvant chemotherapy. A germline pathogenic variant in BReast CAncer gene 2 (BRCA2) was revealed after genetic testing. After 11 months from the completion of adjuvant treatment, she had pulmonary and hilar nodal relapse and began first-line chemotherapy with carboplatin and paclitaxel. However, after only 3 months from starting the treatment, she experienced relevant disease progression, due to the appearance of numerous and symptomatic BMs. Sacituzumab govitecan (10 mg/kg) was started as second-line treatment as part of the Expanded Access Program (EAP). She reported symptomatic relief after the first cycle and received whole-brain radiotherapy (WBRT) concomitantly to sacituzumab govitecan treatment. The subsequent CT scan showed an extracranial partial response and a near-to-complete intracranial response; no grade 3 adverse events were reported, even if sacituzumab govitecan was reduced to 7.5 mg/kg due to persistent G2 asthenia. After 10 months from starting sacituzumab govitecan, a systemic disease progression was documented, while intracranial response was maintained.ConclusionsThis case report supports the potential efficacy and safety of sacituzumab govitecan in the treatment of early recurrent and BRCA-mutant TNBC. Despite the presence of active BMs, our patient had a progression-free survival (PFS) of 10 months in the second-line setting and sacituzumab govitecan was safe when administered together with radiation therapy. Further real-world data are warranted to confirm sacituzumab govitecan efficacy in this patient population.

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“…As reported in the GLOBOCAN 2020 survey, the number of breast cancer (BC) has recently overtaken lung cancer as the most common cancer type worldwide and has become the leading cause of cancer death in women ( 1 ). It has been reported that triple negative breast cancer (TNBC) makes up approximately 15%-20% of all BC patients, which is characterized by estrogen (ER), progesterone (PR), and human epidermal growth factor receptor-2 (HER2) negativity ( 2 ). Due to the variety and heterogeneity, distinct molecular subtypes of TNBC are still not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoints expression patterns in early-stage triple-negative breast cancer predict prognosis and remodel the tumor immune microenvironment

Zhang

Jin²,

Pan³

et al. 2023

Front. Immunol.

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BackgroundCurrently, targeting immune checkpoint molecules holds great promise for triple-negative breast cancer (TNBC). However, the expression landscape of immune checkpoint genes (ICGs) in TNBC remains largely unknown.MethodHerein, we systematically investigated the ICGs expression patterns in 422 TNBC samples. We evaluated the ICGs molecular typing based on the ICGs expression profile and explored the associations between ICGs molecular subtypes and tumor immune characteristics, clinical significance, and response to immune checkpoint inhibitors (ICIs).ResultsTwo ICGs clusters and two ICGs-related gene clusters were determined, which were involved in different survival outcomes, biological roles and infiltration levels of immune cells. We established a quantification system ICGs riskscore (named IRS) to assess the ICGs expression patterns for individuals. TNBC patients with lower IRS were characterized by increased immune cell infiltration, favorable clinical outcomes and high sensitivity to ICIs therapy. We also developed a nomogram model combining clinicopathological variables to predict overall survival in TNBC. Genomic feature analysis revealed that high IRS group presented an increased tumor mutation burden compared with the low IRS group.ConclusionCollectively, dissecting the ICGs expression patterns not only provides a new insight into TNBC subtypes but also deepens the understanding of ICGs in the tumor immune microenvironment.

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Emerging treatment strategies for metastatic triple-negative breast cancer

Cited by 18 publications

References 110 publications

Addiction of Cancer Stem Cells to MUC1-C in Triple-Negative Breast Cancer Progression

Addiction of Cancer Stem Cells to MUC1-C in Triple-Negative Breast Cancer Progression

Sacituzumab govitecan and radiotherapy in metastatic, triple-negative, and BRCA-mutant breast cancer patient with active brain metastases: A case report

Immune checkpoints expression patterns in early-stage triple-negative breast cancer predict prognosis and remodel the tumor immune microenvironment

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