Treatment Of Breast Cancer Research Articles

Performance of sentinel lymph node biopsy after neoadjuvant chemotherapy in clinically node positive breast cancer patients: systematic review and meta-analysis.

The reliability of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) in patients with initially node-positive breast cancer is still controversial. This meta-analysis is conducted to investigate the feasibility and accuracy of SLNB after NACT in patients with initially positive axillary nodes. We conducted a literature search using Medline, PubMed, Embase, Central, and SCOPUS up until April 2021 for studies on the performance of SLNB following NACT. We included prospective studies including breast cancer patients with positive lymph nodes at diagnosis and received NACT before undergoing SLNB irrespective of their molecular subtypes or stage. Our main outcomes of interest were the identification rate (IR) and the false negative rate (FNR) of SLNB. We included an aggregate of 33 studies in this meta-analysis enrolling 4,624 patients. The reported IR ranged from a minimum of 77.6% to a maximum of 100% and resulted in a pooled IR of 88% (95%CI: 86-90, I2:80.9%). The FNR reported in the studies ranged from a minimum of 5.1% to a maximum of 43% and showed a pooled FNR of 13% (95% CI: 11-15, I2: 72.31%). The subgroup analysis demonstrated that the usage of dual mapping technique could decrease the FNR and increase the IR. Moreover, the number of lymph nodes retrieved inversely correlated with FNR (p<0.01). Our findings support the feasibility and accuracy of SLNB after NACT in initially node-positive breast cancer patients, that converted to clinically node negative when performed in properly selected cases. SLNB offers a less invasive approach in selected patients sparing them the morbidity associated with ALND. This approach aligns with efforts to de-escalate surgical management in breast cancer and reinforces that SLNB post-NACT should be incorporated into clinical practice, provided that stringent patient selection and procedural standards are maintained.

Asymptotic analysis of mathematical model describing a new treatment of breast cancer using AZD9496 and palbociclib

Asymptotic analysis of mathematical model describing a new treatment of breast cancer using AZD9496 and palbociclib

Photon mini-GRID therapy for preoperative breast cancer tumor treatment: A treatment plan study.

Breast cancer is the leading cause of female cancer mortality worldwide, accounting for 1 in 6 cancer deaths. Surgery, radiation, and systemic therapy are the three pillars of breast cancer treatment, with several strategies developed to combine them. The association of preoperative radiotherapy with immunotherapy may improve breast cancer tumor control by exploiting the tumor radio-induced immune priming. However, this requires the use of hypofractionated radiotherapy (3×8Gy), increasing the risk of toxicity. Mini-GRID therapy (mini-GRT) is an innovative form of spatially fractionated radiation therapy (SFRT) characterized by narrow beam widths between 1 to 2mm that promises a significant increase in normal tissue dose tolerances and could thereby represent a new alternative for preoperative breast cancer treatment. Mini-GRT has been successfully implemented at the Hospital de Santiago de Compostela (Spain) with a flattening filter-free LINAC (megavoltage x-rays). In this dosimetry proof-of-concept study, we evaluate the feasibility of photon mini-GRT for preoperative breast cancer treatment. We also assess the clinical potential of mini-GRT and compare it with the current treatment standard of intensity-modulated radiotherapy (IMRT). Seven unbiased breast cancer dosimetries of patients treated with stereotactic body radiotherapy (SBRT) (3×8Gy, IMRT) were selected for the study. Photon mini-GRT was compared with SBRT using three main criteria: (i) the dose to organs at risk (OARs), (ii) the dose constraints dictated by normal tissue tolerance, and (iii) the lateral penumbra in OARs. Tumor coverage was evaluated in terms of normalized total dose at 8Gy-fractions. The optimized SBRT by IMRT was realized at the Institut Curie, Paris, France. The dose in mini-GRT was calculated by means of Monte Carlo simulations based on the mini-GRT implementation realized at the University Hospital in Santiago de Compostela. Compared to SBRT plans, mini-GRT resulted in a reduction of the mean dose to the lungs, heart, chest wall, and lymph nodes in the studied cases by a factor ranging from 50% to 100%. Additionally, valley, mean, and peak doses to normal tissues meet the dose tolerance limits for the considered OARs, the most challenging of all being the skin. The mean dose to the skin was reduced (20%-60% less) for most of the studied cases. Mini-GRT also yielded sharper lateral penumbras in the skin and lungs (size reduced by at least 50%). Similar tumor integral doses were obtained for the two treatment modalities. Mini-GRT with megavoltage x-rays is an innovative treatment approach already implemented in a clinical context. In this proof-of-concept study, we evaluated mini-GRT for partial breast cancer irradiation, demonstrating its potential for preoperative treatment thanks to the high skin and normal tissue-sparing capabilities. These initial results represent a first step towards clinical use and encourage further prospective clinical studies.

Delving Into lncRNA-Mediated Regulation of Autophagy-Associated Signaling Pathways in the Context of Breast Cancer.

Breast cancer is a multifaceted and prevalent malignancy, impacting a considerable proportion of women globally. Numerous signaling pathways intricately regulate cellular functions such as growth, proliferation, and survival. Among the various regulators, lncRNAs have emerged as significant players despite their inability to encode proteins. An expanding body of literature underscores the pivotal roles lncRNAs play in cancer biology, particularly in the context of breast cancer. Autophagy, the cellular process dedicated to the degradation and recycling of cellular components, is now recognized as a crucial factor in cancer initiation and progression. The interplay between lncRNAs, various signaling pathways, and autophagy in the pathophysiology of breast cancer remains an active area of investigation. Researchers have identified specific lncRNAs that are dysregulated in breast cancer patients, influencing the modulation of key signaling pathways. Using experimental methodologies and bioinformatics approaches, multiple lncRNAs have been elucidated, providing deeper insights into their contributions to breast cancer pathogenesis and metastatic processes. In summary, the pathophysiological landscape of breast cancer is characterized by the complex interactions involving lncRNA-mediated autophagy. This understanding paves the way for identifying novel therapeutic targets, prognostic markers, and diagnostic markers, ultimately contributing to improved treatment outcomes in breast cancer management.

Targeting MYC for the treatment of breast cancer: use of the novel MYC-GSPT1 degrader, GT19630.

Since MYC is one of the most frequently altered driver genes involved in cancer formation, it is a potential target for new anti-cancer therapies. Historically, however, MYC has proved difficult to target due to the absence of a suitable crevice for binding potential low molecular weight drugs. The aim of this study was to evaluate a novel molecular glue, dubbed GT19630, which degrades both MYC and GSPT1, for the treatment of breast cancer. The antiproliferative potential of GT19630 was evaluated in 14 breast cancer cell lines representing the main molecular subtypes of breast cancer. In addition, we also investigated the effects of GT19630 on apoptosis, cell cycle progression, cell migration, and degradation of the negative immune checkpoint protein, B7-H3. GT19630 inhibited cell proliferation, blocked cell cycle progression, promoted apoptosis, and decreased cell migration at low nanomolar concentrations in breast cancer cell lines. By contrast, previously described MYC inhibitors such as specific MYC-MAX antagonists affected these processes at micromolar concentrations. Consistent with the ability of MYC to promote immune evasion, we also found that GT19630 degraded the negative immune checkpoint inhibitor, B7-H3. We conclude that the novel molecular glue, GT19630, is a potent mediator of endpoints associated with cancer formation/progression. Its ability to degrade B7-H3 suggests that GT19630 may also promote host immunity against cancer. To progress GT19630 as a therapy for breast cancer, our finding should now be confirmed in an animal model system.

18F-FDG PET/CT radiomic analysis and artificial intelligence to predict pathological complete response after neoadjuvant chemotherapy in breast cancer patients.

Build machine learning (ML) models able to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients based on conventional and radiomic signatures extracted from baseline [18F]FDG PET/CT. Primary tumor and the most significant lymph node metastasis were manually segmented in baseline [18F]FDG PET/CT of 52 newly diagnosed BC patients. Clinical parameters, NAC and conventional semiquantitative PET parameters were collected. The standard of reference considered was surgical pCR after NAC (ypT0;ypN0). Eight-hundred-fifty-four radiomic features (RFts) were extracted from both PET and CT datasets, according to IBSI; robust RFTs were selected. The cohort was split in training (70%) and validation (30%) sets. Four ML Models (Clinical Model, CT Model, PET Model_T and PET Model_T + N) each one with 3 learners (Random Forest (RF), Neural Network and Stochastic Gradient Descendent) were trained and tested using RFts and clinical signatures. PET Models were built considering robust RFTs extracted from either primary tumor alone (PET Model_T) or also including the reference lymph node (PET Model_T + N). 72 pathological uptakes (52 primary BC and 20 lymph node metastasis) at [18F]FDG PET/CT were segmented. pCR occurred in 44.2% cases. Twelve, 46 and 141 robust RFts were selected from CT Model, PET Model_T and PET Model_T + N, respectively. PET Models showed better performance than CT and Clinical Models. The best performances were obtained by the RF algorithm of the PET Model_T + N (AUC = 0.83;CA = 0.74;TP = 78%;TN = 72%). ML models trained on PET/CT radiomic features extracted from primary BC and lymph node metastasis could concur in the prediction of pCR after NAC and improve BC management.

Receptor CDCP1 is a potential target for personalized imaging and treatment of poor outcome HER2+, triple negative and metastatic ER+/HER2- breast cancers.

Receptor CUB-domain containing- protein 1 (CDCP1) was evaluated as a target for detection and treatment of breast cancer. CDCP1 expression was assessed immunohistochemically in tumors from 423 patients (119 triple-negative breast cancer (TNBC); 75 HER2+; 229 ER+/HER2- including 228 primary tumors, 229 lymph node and 47 distant metastases). Cell cytotoxicity induced in vitro by a CDCP1-targeting antibody-drug conjugate (ADC), consisting of the human/mouse chimeric antibody ch10D7 and the microtubule disruptor monomethyl auristatin E (MMAE), was quantified, including in combination with HER2-targeting ADC T-DM1. Detection of CDCP1-expressing primary and metastatic xenografts in mice was examined by PET-CT imaging using 89zirconium-labelled ch10D7 (89Zr-ch10D7). The impact of ch10D7-MMAE on tumor burden and survival in vivo, including in combination with T-DM1, was quantified in cell line and patient-derived xenograft mouse models. CDCP1 is expressed predominantly on the surface of malignant cells of 70% of TNBCs, 80% of HER2+ tumors, and increases in ER+/HER2- tumors from 44.9% in primary tumors to 56.4% in lymph node metastases and 74.3% in distant metastases. PET-CT imaging with 89Zr-ch10D7 is effective for the detection of primary and metastatic CDCP1-expressing TNBCs in mice. ADC ch10D7-MMAE kills CDCP1-expressing cells in vitro and controls primary and metastatic TNBC xenografts in mice, conferring significant survival advantages over chemotherapy. It compares favorably to T-DM1 in vivo, and ch10D7-MMAE combined with T-DM1 showed the most potent efficacy, markedly reducing tumor burden of CDCP1+/HER2+ xenografts and prolonging mouse survival, compared with T-DM1 or ch10D7. CDCP1-directed molecular imaging has potential to identify aggressive breast cancers for CDCP1-targeted treatment.

Musculoskeletal symptoms associated with aromatase inhibitors in the treatment of early breast cancer: A scoping review of risk factors and outcomes.

Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) are the most common adverse effects experienced by breast cancer patients. This scoping review aimed to systematically synthesize the predictors/risk factors and outcomes of AIMSS in patients with early-stage breast cancer. A systematic search was conducted in PubMed, Web of Science, EMBASE, CINAHL, and the China National Knowledge Internet (CNKI) from inception to December 2024 following the scoping review framework proposed by Arksey and O'Malley (2005). A total of 5,008 studies were identified, and 98 were included in this review. The risk factors for AIMSS included psychosocial and demographic factors (e.g., age, BMI, menstrual status, and anxiety), clinical factors (e.g., history of chemotherapy, preexisting pain, and musculoskeletal diseases) and gene polymorphisms (e.g., ESR1, OPG, RANKL, TCL1A, and CYP19A1). The outcomes of AIMSS encompassed physical, psychological, behavioral, and survival-related impacts. This scoping review synthesized the available evidence on predictors, risk factors, and outcomes of AIMSS, providing a foundation for developing risk prediction models and enhancing symptom management strategies.

An Investigation of Travel Distance and Timeliness of Breast Cancer Treatment Among a Diverse Cohort in the United States

Travel to and from distant cancer treatment facilities can place a significant burden on cancer patients, particularly rural and minority survivors. Thus, the purpose of our investigation was to examine the association between patient travel distance and delays in types of treatment for breast cancer (surgery, radiation, chemotherapy, and hormonal therapy) and treatment delays. Using a novel linkage between the state cancer registry and administrative data from Medicaid and a private insurance plan, 2155 BC patients were successfully linked to create the cohort. ArcGIS was used to geocode all case residences and treatment facility addresses and calculate network distance between the residence and each facility. Logistic regression models were used to calculate the adjusted odds of being delayed versus timely by street distance. Odds of late surgery were increased by 1% (95% CI: 1.00, 1.01) for each one-mile increase from the patient’s residence to the treatment facility. In race-stratified models, the odds of late treatment for Black patients increased by 3% per mile (95% CI 1.01, 1.06) for radiation. Increased travel distance appears to significantly increase treatment delays for surgical, radiation, and chemotherapeutic treatments for women with BC, especially among Black women.

Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer.

This study presents T-1-NBAB, a new compound derived from the natural xanthine alkaloid theobromine, aimed at inhibiting VEGFR-2, a crucial protein in angiogenesis. T-1-NBAB's potential to interacts with and inhibit the VEGFR-2 was indicated using in silico techniques like molecular docking, MD simulations, MM-GBSA, PLIP, essential dynamics, and bi-dimensional projection experiments. DFT experiments was utilized also to study the structural and electrostatic properties of T-1-NBAB. Computational analysis was performed to predict the ADME-Tox profiles of T-1-NBAB. After semisynthesis, the in vitro results showed that T-1-NBAB effectively inhibits VEGFR-2, with an IC50 of 0.115 μM, compared to sorafenib's 0.0591 μM. In vitro tests also demonstrated significant activity of T-1-NBAB against breast cancer cell lines MCF7 and T47D, with IC50 values of 16.88 μM and 61.17 μM, respectively, and high selectivity. Importantly, T-1-NBAB induced early and late apoptosis in MCF7 cells, indicating its potential as a strong anticancer agent. Additionally, T-1-NBAB reduced the migration and healing abilities of MCF7 cells, suggesting it could be a promising anti-angiogenic agent. Overall, these findings suggest that T-1-NBAB is a promising lead compound for further research as a potential treatment for breast cancer.

Non-hormonal management of vasomotor symptoms during and after primary breast cancer treatment

Non-hormonal management of vasomotor symptoms during and after primary breast cancer treatment

Potential of Bioactive Compounds In Coleus amboinicus, Lour., Leaves Against Breast Cancer By Assessment Using A Network Pharmacology Approach and Cytotoxic Test

Breast cancer is a disease that significantly contributes to global women death. The study aims to conduct in vitro activity testing and assessment with a bioinformatics approach using a pharmacological network of bioactive compounds from bangun-bangun (Coleus amboinicus) leaves extract as a breast cancer drug. The methods used are extraction of bioactive compounds by maceration and partition, identification and analysis of bioactive compounds using the Liquid Chromatography High-Resolution Mass Spectrometry (LC-HRMS) instrument, cytotoxic testing of breast cancer cells (MCF-7) and normal cells (CV-1) with the MTT method, and assessment with a bioinformatics approach through a network pharmacology. The results of the cytotoxic test of ethyl acetate extract provided better activity with IC50 value of 102.30 and 457.09 µg/mL against MCF-7 cancer cells and CV-1 normal cells. The selectivity index value of 4.23 indicates the potential for further development in the treatment of breast cancer. The results of the analysis of chemical compound content show various types of potential bioactive compounds as breast cancer anticancer; assessment of the bioinformatics approach through networks pharmacology with pathways in cancer provides predictions of signal transducer and activator of transcription 3 (STAT3) protein as the main therapeutic mechanism target in breast cancer treatment. This study provides initial information for further research on testing and utilizing bioactive compounds from C. amboinicus leaves as an alternative treatment for breast cancer.

In situ generation of Copper sulfide within Poly(lactic-co-glycolic acid): A strategy for Safer photothermal therapy in Triple-Negative breast cancer.

Copper sulfide nanoparticles (CuS NPs) have garnered significant attention in photothermal therapy (PTT) owing to their facile synthesis, biodegradability, stability, and excellent photothermal conversion efficiency. Nonetheless, their potential toxic effects have restricted their application. This research focuses on the encapsulation of CuS NPs with the biocompatible polymer poly(lactic-co-glycolic acid) (PLGA) to enhance their biocompatibility, thereby improving the efficacy and safety of PTT in the treatment of triple-negative breast cancer (TNBC). Three distinct methods, namely aqueous phase loading method, oil phase loading method, and "in situ reduction" method were employed to synthesize PLGA-coated CuS (CuS@PLGA) NPs to optimize the encapsulation rate of CuS. Among these, the CuS@PLGA NPs fabricated via the "in situ reduction" method demonstrated the highest encapsulation efficiency for CuS, achieving a rate of (90.4 ± 3.3)%. The resulting CuS@PLGA NPs exhibited high stability, excellent photothermal effect, and good tumor-targeting ability. Moreover, CuS@PLGA NPs demonstrated enhanced anti-tumor efficacy and biocompatibility compared to CuS NPs in both in vitro and in vivo experiments. Consequently, this study offers an effective and safety strategy for PTT treatment of TNBC.

Did the COVID-19 consortium recommendations impact the treatment of breast cancer during the COVID-19 pandemic?

We examined the impact of the COVID-19 consortium recommendations on the surgical management of breast cancer during the first year of the pandemic. Patients with newly diagnosed ER + DCIS, ER- DCIS, AJCC Stage cT1-2N0-1 ER + , HER2-, HER2 + , and triple negative breast cancer were identified from the National Cancer Database from 2018 to 2021. An interrupted time series design evaluated differences in surgical delay and use of neoadjuvant chemotherapy/immunotherapy (NAC) and endocrine therapy (NET) before and after the pandemic. A total of 895116 female patients were included in the study with a mean age of 61.7years. Time to surgery decreased by an average 5.5days from January 2020 to May 2020 for all breast cancer types, corresponding with a 62.2% decrease in breast cancer diagnoses per month from January 2020 to April 2020. The use of NET increased from 5.6 to 23.6% from January to March 2020 for patients with ER + DCIS and 8.0 to 31.1% for ER + cT1-2N0 cancer (both p < 0.01). The use of NAC for HER2 + tumors and triple negative breast cancers has been increasing since 2018 and a larger than expected increase was seen from 57.2 to 63.6% for HER2 + tumors and 55.6 to 68.7% for triple negative breast cancers (both p < 0.01). Treatment practices returned to pre-pandemic levels in June 2020. Prior to the publication of the Consortium recommendations, time to surgery decreased while the use of NET and NAC increased, with the resumption of pre-pandemic practices by June 2020.

Global transcriptome profiling of ST09 treated breast cancer cells identifies miR-197-5p/GPX3 antioxidant axis as a regulator of tumorigenesis.

ROS (Reactive Oxygen Species) has a dual role in tumorigenesis. Some cancers have high ROS conditions, and others have low ROS. TNBC thrives on high ROS compared to other Breast Cancer subtypes. Several antioxidant enzymes catalyze the detoxification of reactive oxygen species and prevent free radicals from damaging DNA and accumulation of mutation. Curcumin, a polyphenol dietary supplement, acts as a potent antioxidant, is known to reduce inflammation, and has anticancer properties. Here, we aim to understand alterations in the transcriptome (miRNA and mRNA expression) induced by ST09 in breast cancer cell lines. We identified an antioxidant system that is upregulated in breast cancer cell lines. Among the antioxidant enzymes regulated by miRNA was GPX3. A novel miRNA-mRNA antioxidant axis, miR-197-5p/GPX3, was observed in the TNBC cell line. We further validated the regulation of GPX3 by miRNA using luciferase assay. GPX3 overexpression, knockdown, and activity assay indicated the anti-tumorigenic role of GPX3 in the TNBC cell line. Further, treatment of TNBC xenograft with ST09 showed tumor reduction in vivo. ST09 potentiates the effect of standard-of-care (SOC) drug Cisplatin in vivo. ST09 can be exploited as a single chemotherapeutic agent or in combination treatment modalities, reducing the dosage of potent drugs.

Investigation of Aframomum melegueta compounds as ERK5 inhibitor related to breast cancer via molecular docking and dynamic simulation.

The molecular docking study of Dihydrogingerenone A, 1-(3, 4-dihydroxy-5-methoxyphenyl)-7-(3, 4-dihydroxyphenyl) heptane-3, 5-diyldiacetate, and Dihydrogingerenone C from Aframomum melegueta as effective breast cancer treatment.

Liquid biopsy technologies: innovations and future directions in breast cancer biomarker detection.

Globally, breast cancer is the most frequent type of cancer, and its early diagnosis and screening can significantly improve the probability of survival and quality of life of those affected. Liquid biopsy-based targets such as circulating tumor cells, circulating tumor DNA, and exosomes have been instrumental in the early discovery of cancer, and have been found to be effective in stage therapy, recurrence monitoring, and drug selection. Biosensors based on these target related biomarkers convert the tested substances into quantifiable signals such as electrical and optical signals through signal transduction, which has the advantages of high sensitivity, simple operation, and low invasiveness. This review provides an overview of the latest progress of liquid biopsy biomarkers in the diagnosis, prognosis and treatment of breast cancer, compares the application and advantages of different biosensors based on these biomarkers in the diagnosis of breast cancer, and analyzes the limitations and solutions of biosensor based methods.

Harnessing Polyphenols and Novel Delivery Strategies for Effective Treatment of Breast Cancer.

Breast cancer continues to pose a significant global health challenge, with conventional therapies frequently hindered by resistance mechanisms and undesirable side effects. This review investigates the therapeutic potential of polyphenols-naturally occurring compounds recognized for their antioxidant, anti-inflammatory, and anti-cancer properties-as alternative or complementary treatments for breast cancer. We examine the molecular pathways through which polyphenols exert their effects, including their influence on oxidative stress modulation, inflammatory responses, cellular proliferation, apoptosis, and estrogen receptor signalling. Additionally, this review addresses innovative nano-based drug delivery systems such as nanoparticles, liposomes, niosomes, and phytosomes that enhance the stability, bioavailability, and targeted delivery of polyphenols. These advanced formulations aim to overcome challenges related to polyphenol degradation, low solubility, and rapid systemic clearance, thereby enhancing their therapeutic efficacy. Through a detailed analysis, we assess the contributions of various nanocarriers in optimizing the delivery of polyphenols specifically to breast cancer cells while minimizing systemic toxicity. The evidence presented highlights the potential of polyphenols in breast cancer management, further supported by nanoformulations that improve both stability and delivery efficiency.

Interactions between the tumor microbiota and breast cancer

Breast cancer is the most common malignancy in women worldwide. Changes in the microbiota and their metabolites affect the occurrence and development of breast cancer; however, the specific mechanisms are not clear. Gut microbes and their metabolites influence the development of breast cancer by regulating the tumor immune response, estrogen metabolism, chemotherapy, and immunotherapy effects. It was previously thought that there were no microorganisms in breast tissue, but it is now thought that there are microorganisms in breast cancer that can affect the outcome of the disease. This review builds on existing research to comprehensively analyze the role of gut and intratumoral microbiota and their metabolites in the development and metastasis of breast cancer. We also explore the potential function of the microbiota as biomarkers for prognosis and therapeutic response, highlighting the need for further research to clarify the causal relationship between the microbiota and breast cancer. We hope to provide new ideas and directions for the development of new methods for breast cancer treatment.

Accumulation of CD38 in Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling and Metastasis in Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. The epithelial-to-mesenchymal transition is a nonbinary process in the metastatic cascade that generates tumor cells with both epithelial and mesenchymal traits known as hybrid EM cells. Recent studies have elucidated the enhanced metastatic potential of cancers featuring the hybrid EM phenotype, highlighting the need to uncover molecular drivers and targetable vulnerabilities of the hybrid EM state. Here, we discovered that hybrid EM breast tumors are enriched in CD38, an immunosuppressive molecule associated with worse clinical outcomes in liquid malignancies. Altering CD38 expression in tumor cell impacted migratory, invasive, and metastatic capabilities of hybrid EM cells. Abrogation of CD38 expression stimulated an antitumor immune response, thereby preventing the generation of an immunosuppressive microenvironment in hybrid EM tumors. CD38 levels positively correlated with PD-L1 expression in samples from patients with TNBC. Moreover, targeting CD38 potentiated the activity of anti-PD-L1, eliciting strong antitumor immunity, with reduced tumor growth in hybrid EM models. Overall, this research exposes upregulation of CD38 as a specific survival strategy utilized by hybrid EM breast tumors to suppress immune cell activity and sustain metastasis, with strong implications in other carcinomas that have hybrid EM properties. Significance: Hybrid cells co-featuring epithelial and mesenchymal traits in triple-negative breast cancer express elevated levels of CD38 to induce immunosuppression and metastasis, indicating CD38 inhibition as potential strategy for treating breast cancer.