Publications by authors named "Cesar Santa-Maria"

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options, which warrants the identification of novel therapeutic targets. Deciphering nuances in the tumor microenvironment (TME) may unveil insightful links between antitumor immunity and clinical outcomes; however, such connections remain underexplored. Here, we employed a data set derived from imaging mass cytometry of 71 TNBC patient specimens at single-cell resolution and performed in-depth quantifications with a suite of multiscale computational algorithms.

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  • * A study used advanced modeling and data analysis to assess 90 potential biomarkers, finding that using combinations of these markers increased specificity but decreased sensitivity.
  • * Notably, early on-treatment biomarkers, like monitoring tumor size changes two weeks after starting treatment, displayed better accuracy, and blood-based biomarkers were also effective, offering a less invasive method for identifying responsive patients.
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  • The study discusses a patient with metastatic breast cancer who has a genetic mutation in the PALB2 gene, which is linked to DNA repair processes.
  • The patient developed resistance to a class of drugs known as PARP inhibitors (PARPi) after initial treatment, raising concerns about treatment effectiveness.
  • Researchers found that the cancer evolved in multiple ways (convergent evolution) to develop this resistance, highlighting the complexity of managing cancer treatments over time.
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  • Hypoxia, which is a lack of oxygen, happens in most solid tumors and can lead to cancer spreading and worse outcomes for patients.
  • Breast cancer cells that are low in oxygen are much more likely to spread to the lungs in experiments with animals.
  • By studying how these cancer cells behave, researchers found that blocking a specific protein called MUC1 can help stop the cancer from spreading and could lead to better treatments.
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  • Breast cancer treatment involves a team of specialists from surgical, radiation, and medical oncology fields.
  • The NCCN Guidelines provide recommendations for various types of breast cancer, including different stages and specific conditions like Paget's disease and treatment during pregnancy.
  • This issue highlights the management of systemic therapies for nonmetastatic breast cancer, both before and after surgery.
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  • Patients with early-stage triple-negative breast cancer (TNBC) face a high risk of recurrence after treatment, even when receiving pembrolizumab alongside chemotherapy.
  • Sacituzumab govitecan, which combines an antibody-drug conjugate with a topoisomerase I inhibitor, shows significant improvement in progression-free survival and overall survival for pre-treated metastatic TNBC compared to traditional chemotherapy.
  • The international phase III AFT-65/ASCENT-05/OptimICE-RD trial aims to assess the effectiveness and safety of sacituzumab govitecan combined with pembrolizumab versus physician's choice treatment for early-stage TNBC patients who have residual disease post-neoadjuvant therapy, and is currently recruiting participants
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Patients with metastatic triple-negative breast cancer (TNBC) show variable responses to PD-1 inhibition. Efficient patient selection by predictive biomarkers would be desirable, but is hindered by the limited performance of existing biomarkers. Here, we leveraged in-silico patient cohorts generated using a quantitative systems pharmacology model of metastatic TNBC, informed by transcriptomic and clinical data, to explore potential ways to improve patient selection.

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The tumor microenvironment is widely recognized for its central role in driving cancer progression and influencing prognostic outcomes. There have been increasing efforts dedicated to characterizing this complex and heterogeneous environment, including developing potential prognostic tools by leveraging modern deep learning methods. However, the identification of generalizable data-driven biomarkers has been limited, in part due to the inability to interpret the complex, black-box predictions made by these models.

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Unlabelled: Combinations of immune checkpoint inhibitors (ICI, including anti-PD-1/PD-L1) and chemotherapy have been FDA approved for metastatic and early-stage triple-negative breast cancer (TNBC), but most patients do not benefit. B7-H4 is a B7 family ligand with proposed immunosuppressive functions being explored as a cancer immunotherapy target and may be associated with anti-PD-L1 resistance. However, little is known about its regulation and effect on immune cell function in breast cancers.

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  • Triple-negative breast cancer (TNBC) is known for its aggressiveness and lack of effective treatments, leading researchers to search for new therapeutic targets by studying the tumor microenvironment (TME).* -
  • By analyzing imaging mass cytometry data from 58 TNBC patient samples, distinct patterns in cell distribution were found, revealing important links between tumor characteristics, immune factors, and patient survival.* -
  • Using machine learning on engineered spatial data, researchers achieved a predictive accuracy of 0.71 for patient treatment responses based on TME features, highlighting the potential of using TME architecture as a basis for new treatment strategies in TNBC.*
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Importance: Agents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the standard of care in patients with PD-L1-positive metastatic disease. In contrast to microtubule-targeting agents, the effect of combining platinum compounds with programmed cell death 1 (PD-1)/PD-L1 immunotherapy has not been extensively determined.

Objective: To evaluate the efficacy of atezolizumab with carboplatin in patients with metastatic TNBC.

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Tebotelimab, a bispecific PD-1×LAG-3 DART molecule that blocks both PD-1 and LAG-3, was investigated for clinical safety and activity in a phase 1 dose-escalation and cohort-expansion clinical trial in patients with solid tumors or hematologic malignancies and disease progression on previous treatment. Primary endpoints were safety and maximum tolerated dose of tebotelimab when administered as a single agent (n = 269) or in combination with the anti-HER2 antibody margetuximab (n = 84). Secondary endpoints included anti-tumor activity.

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Unlabelled: Despite the success of immune checkpoint inhibition (ICI) in treating cancer, patients with triple-negative breast cancer (TNBC) often develop resistance to therapy, and the underlying mechanisms are unclear. MHC-I expression is essential for antigen presentation and T-cell-directed immunotherapy responses. This study demonstrates that TNBC patients display intratumor heterogeneity in regional MHC-I expression.

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Purpose: Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during adjuvant ET will enhance symptom detection, symptom management, and persistence.

Methods: Eligible patients were initiating ET for stage 0-III breast cancer.

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Triple-negative breast cancer (TNBC), a highly metastatic breast cancer subtype, has limited treatment options. While a small number of patients attain clinical benefit with single-agent checkpoint inhibitors, identifying these patients before the therapy remains challenging. Here, we developed a transcriptome-informed quantitative systems pharmacology model of metastatic TNBC by integrating heterogenous metastatic tumors.

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Purpose: For patients treated with neoadjuvant chemotherapy (NAC) for breast cancer, it is standard of care to perform pre- and post-NAC imaging to evaluate response to therapy prior to surgery. In this study we assess outcome metrics of magnetic resonance imaging (MRI) following NAC.

Methods: We conducted a retrospective analysis of patients with invasive breast cancer who underwent a breast MRI before and after NAC between 2016 and 2021 at a single, multisite academic institution.

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Recent advances in spatial transcriptomics (STs) enable gene expression measurements from a tissue sample while retaining its spatial context. This technology enables unprecedented in situ resolution of the regulatory pathways that underlie the heterogeneity in the tumor as well as the tumor microenvironment (TME). The direct characterization of cellular co-localization with spatial technologies facilities quantification of the molecular changes resulting from direct cell-cell interaction, as it occurs in tumor-immune interactions.

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Purpose: Cancers deficient in homologous recombination DNA repair, such as those with BRCA1 or BRCA2 (BRCA1/2) mutations rely on a pathway mediated by the enzyme poly(adenosine diphosphate-ribose) polymerase (PARP). PARP inhibitors (PARPi's) have demonstrated efficacy in treating patients with germline (g)BRCA1/2, somatic (s)BRCA1/2, and gPALB2 mutations in clinical trials. However, patients with a poor performance status (PS) and those with severe organ impairment are often excluded from clinical trials and cancer-directed treatment.

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Introduction: In contrast to other breast cancer subtypes, there are currently limited options of targeted therapies for triple-negative breast cancer (TNBC). Immense research has demonstrated that not only cancer cells but also stromal cells and immune cells in the tumor microenvironment (TME) play significant roles in the progression of TNBC. It is thus critical to understand the components of the TME of TNBC and the interactions between the various cell populations.

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Introduction: Palbociclib is highly efficacious and well tolerated in hormone-receptor positive (HR+) metastatic breast cancer (BC) but its activity for HER2+ BC with brain metastases (BM) is unknown.

Methods: In a single-arm phase II study we evaluated palbociclib with trastuzumab for patients with HER2+ MBC and BM. The primary endpoint was BM response rate.

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Atezolizumab with chemotherapy has shown improved progression-free and overall survival in patients with metastatic PD-L1 positive triple negative breast cancer (TNBC). Atezolizumab with anthracycline- and taxane-based neoadjuvant chemotherapy has also shown increased pathological complete response (pCR) rates in early TNBC. This trial evaluated neoadjuvant carboplatin and paclitaxel with or without atezolizumab in patients with clinical stages II-III TNBC.

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Purpose: To examine the relationship between daily fluctuations in symptoms and sedentary behavior (SB) during chemotherapy (CT) for breast cancer.

Methods: Breast cancer patients ( N = 68, M age = 48.5 ± 10.

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