Sylvia Adams's research while affiliated with NYU Langone Medical Center and other places

Publications (140)

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The importance of integrating biomarkers into the TNM staging has been emphasized in the 8 th Edition of the American Joint Committee on Cancer (AJCC) Staging system. In a pooled analysis of 2148 TNBC-patients in the adjuvant setting, TILs are found to strongly up and downstage traditional pathological-staging in the Pathological and Clinical Progn...
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1078 Background: In the IMpassion130 study (NCT02425891) first-line atezolizumab plus nab-paclitaxel (A+nP) provided clinical benefit compared with placebo plus nP (P+nP) in patients with mTNBC whose tumors were PD-L1+ (Schmid NEJM 2018). However, in many patients, disease that was initially controlled eventually progressed. The mechanism of action...
Article
e12633 Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer with poor prognosis and is often resistant to neoadjuvant systemic therapy with early recurrence and metastases. PD-L1 expression in IBC is moderate to high, and blockade of the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a promising treat...
Article
1083 Background: The immune checkpoint inhibitor (ICI) atezo showed disparate outcomes as first-line therapy for metastatic TNBC when combined with nab-paclitaxel (nPac) in IMpassion130 [Schmid 2018] vs solvent-based paclitaxel (Pac) in IMpassion131 [Miles 2021]. A key difference between the trials was use of steroid premedication for Pac in IMpass...
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Introduction There is evidence that supports the association of dense tumor infiltrating lymphocyte (TILs) with an increased risk of ipsilateral recurrence in ductal carcinoma in situ (DCIS). However, the association of cellular composition of DCIS immune microenvironment with the histopathologic parameters and outcome is not well understood. Meth...
Preprint
Purpose The functional composition and diversity of the gut microbiome (estrobolome) may affect breast cancer risk by modulation of systemic sex hormones. Gut bacteria with β-glucuronidase enzymatic activity may deconjugate estrogens, leading to increased estrogen reabsorption into the circulation thereby increasing breast cancer risk. We investiga...
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Background: Black patients with triple negative breast cancer (TNBC) have worse survival outcomes, even after adjusting for stage at diagnosis, income, insurance status and other socioeconomic factors. Little is known regarding anti-tumor immune responses in Black patients and how these differences affect responses to treatment in TNBC. Limited dat...
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Purpose Provide real-world data regarding the risk for SARS-CoV-2 infection and mortality in breast cancer (BC) patients on active cancer treatment. Methods Clinical data were abstracted from the 3778 BC patients seen at a multisite cancer center in New York between February 1, 2020 and May 1, 2020, including patient demographics, tumor histology,...
Article
Resistance to targeted therapies is an important clinical problem in HER2-positive (HER2+) breast cancer. "Drug-tolerant persisters" (DTP), a subpopulation of cancer cells that survive via reversible, nongenetic mechanisms, are implicated in resistance to tyrosine kinase inhibitors (TKI) in other malignancies, but DTPs following HER2 TKI exposure h...
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The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed dea...
Article
Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately eight months for metastatic disease. We report results for advanced MpBC treated with ipilimumab+nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Methods: Prospective, open-label, multicent...
Article
Tumor-associated macrophages (TAMs) promote metastasis and inhibit T cells, but macrophages can be polarized to kill cancer cells. Macrophage polarization could thus be a strategy for controlling cancer. We show that macrophages from metastatic pleural effusions of breast cancer patients can be polarized to kill cancer cells with monophosphoryl lip...
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Breast cancer has historically been a disease for which immunotherapy was largely unavailable. Recently, the use of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for the treatment of advanced/metastatic triple-negative breast cancer (TNBC) has demonstrated efficacy, including longer progression-free survival and increased ove...
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Background: In the Phase III IMpassion130 study, atezolizumab plus nab-paclitaxel (A+nP) showed clinical benefit in advanced/metastatic triple-negative breast cancer (TNBC) patients who were programmed death-ligand 1 (PD-L1) + (tumor-infiltrating immune cells [IC] ≥1%) using the SP142 immunohistochemistry (IHC) assay. Here we evaluate 2 other PD-L...
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COVID‐19 can be especially dangerous in vulnerable populations such as those with cancer undergoing treatment. When it is discovered in an asymptomatic patient through imaging, there is a paucity of evidence‐based treatment recommendations. COVID‐19 can be especially dangerous in vulnerable populations such as those with cancer undergoing treatment...
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TPS5600 Background: KIF18A is a mitotic kinesin motor protein that regulates chromosome positioning during cell division and is overexpressed in a subset of human cancers. TP53 mutant unstable aneuploid cancer cells with chromosomal instability (CIN) features are dependent on KIF18A motor activity to prevent lethal multipolar cell division. Preclin...
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1513 Background: In high-risk estrogen-receptor positive, HER2 positive, or triple negative breast cancer (BC), chemotherapy can increase cure rates in early-stage disease and prolong survival in setting of advanced disease. Real world data specific to BC is needed to counsel patients (pts) with BC on their risk for SARS-CoV-2 infection and mortali...
Article
1006 Background: IMpassion130 was the first randomized phase 3 study to show clinical benefit of cancer immunotherapy (CIT) in untreated PD-L1+ mTNBC. Enhanced A + nP efficacy vs placebo (P) + nP was seen in pts with a richer immune TME but was confined to PD-L1 IC+ pts (PD-L1–expressing immune cells on ≥1% of tumor area; Emens JNCI 2021). While TN...
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The purpose of this work was to develop a novel method to disentangle the intra- and extracellular components of the total sodium concentration (TSC) in breast cancer from a combination of proton ( $$^{1}$$ 1 H) and sodium ( $$^{23}\hbox {Na}$$ 23 Na ) magnetic resonance imaging (MRI) measurements. To do so, TSC is expressed as function of the intr...
Conference Paper
Background: Neoadjuvant endocrine therapy has traditionally been considered a treatment option for locally advanced and/or surgically high-risk women with hormone positive disease. Early stage hormone-positive breast cancer, on the other hand, is usually managed with upfront surgery, with post-operative hormone therapy as a risk-reducing adjunct. D...
Conference Paper
Background: The clinical implications of genomic alterations in metastatic triple-negative breast cancer (mTNBC) have not been clearly addressed. In IMpassion130, atezolizumab (A) + -paclitaxel (nP) showed improved progression-free survival (PFS) and clinically meaningful overall survival (OS) benefit vs placebo (P) + nP in PD-L1+ mTNBC (Schmid, NE...
Conference Paper
Background: In the phase 2 KEYNOTE-086 study (NCT02447003), pembrolizumab monotherapy had durable antitumor activity in a subset of patients with previously treated mTNBC (cohort A; n = 170) and in patients with previously untreated PD-L1-positive mTNBC (cohort B; n = 84). In this exploratory analysis of KEYNOTE-086, we evaluated the association be...
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Background Understanding the impact of the tumor immune microenvironment and BRCA-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors may help optimize both patient and treatment selection in metastatic triple-negative breast cancer (mTNBC). In this substudy from the phase 3 IMpassion130 trial, immune biomarkers...
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Purpose: Immunotherapy has recently been shown to improve outcomes for advanced PD-L1-positive triple-negative breast cancer (TNBC) in the Impassion130 trial, leading to FDA approval of the first immune checkpoint inhibitor in combination with taxane chemotherapy. To further develop predictive biomarkers and improve therapeutic efficacy of the com...
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Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research comm...
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Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variabili...
Article
Knowledge of fundamental differences between breast cancer subtypes has driven therapeutic advances; however, basal-like breast cancer (BLBC) remains clinically intractable. Because BLBC exhibits alterations in DNA repair enzymes and cell-cycle checkpoints, elucidation of factors enabling the genomic instability present in this subtype has the pote...
Preprint
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Many cancers recruit monocytes/macrophages and polarize them into tumor-associated macrophages (TAMs). TAMs promote tumor growth and metastasis and inhibit cytotoxic T cells. Yet, macrophages can also kill cancer cells after polarization by e.g., lipopolysaccharide (LPS, a bacteria-derived toll-like receptor 4 [TLR4] agonist) and interferon gamma (...
Article
1073 Background: Immune checkpoint blockade, specifically anti-CTLA-4 and anti-PD-1-directed approaches, has improved outcomes in various tumors and is being tested in SWOG S1609 in rare solid tumors (DART=Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors). Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer with poor response to...
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Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management frame...
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Immune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the a...
Conference Paper
Background: In the Phase 3 IMpassion130 (NCT02425891) trial in metastatic triple-negative breast cancer (mTNBC), first-line atezolizumab + -paclitaxel (A+nP) significantly improved PFS vs placebo + -paclitaxel (P+nP) in the intent-to-treat (ITT) and PD-L1+ (PD-L1-stained immune cells [IC] ≥ 1% of the tumor area by VENTANA PD-L1 SP142 assay) populat...
Conference Paper
BACKGROUND: Receptor activator of NF-kB (RANK) and its ligand (RANKL) have a well-established role in osteoclast-driven bone remodeling, however RANK/RANKL expression can also be seen on mammary epithelial cells and immune cells (IC). In breast cancer (BC) mouse models, RANKL is a paracrine effector of the mitogenic activity of progesterone and inh...
Conference Paper
Background: eTNBC remains at high risk for recurrence despite modern (neo)adjuvant chemotherapy. Immunotherapy with checkpoint inhibition is active in early and metastatic TNBC, and vaccines may further induce host immune response. PVX-410 (PVX, OncoPep) is a novel tetra-peptide vaccine with 3 of the 4 antigens (XBP1 [2 splice variants] and CD138)...
Conference Paper
Introduction: Breast carcinomas can be classified by hormone receptors and human epidermal growth factor receptor-2 (HER-2) status. HER-2 status is assessed using immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH). Immunophenotypic triple negative breast cancers (iTNBC) may harbor an amplification of HER-2 detected by FISH (...
Article
Background: Patients with triple-negative breast cancer (TNBC) with homologous recombination deficient tumors achieve significantly higher pathologic complete response (pCR) rates when treated with neoadjuvant platinum-based therapy. Tumor infiltrating lymphocytes (TILs) are prognostic and predictive of chemotherapy benefit in early stage TNBC. Th...
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Antibodies blocking programmed death 1 (anti-PD-1) or its ligand (anti-PD-L1) are associated with modest response rates as monotherapy in metastatic breast cancer, but are generally well tolerated and capable of generating dramatic and durable benefit in a minority of patients. Anti-PD-1/L1 antibodies are also safe when administered in combination...
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Historically, breast cancer tumors have been considered immunologically quiescent, with the majority of tumors demonstrating low lymphocyte infiltration, low mutational burden, and modest objective response rates to anti-PD-1/PD-L1 monotherapy. Tumor and immunologic profiling has shed light on potential mechanisms of immune evasion in breast cancer...
Article
Background: Immunotherapy in combination with chemotherapy has shown promising efficacy across many different tumour types. We report the prespecified second interim overall survival analysis of the phase 3 IMpassion130 study assessing the efficacy and safety of atezolizumab plus nab-paclitaxel in patients with unresectable, locally advanced or me...
Article
In Reply We appreciate the letter by Yang and the opportunity to comment on the safety of immune checkpoint blockade (ICB) in breast cancer. This important subject was not addressed extensively in our original article due to space limitations.¹ However, since that publication, a comprehensive review by D’Abreo and Adams² on the incidence of adverse...
Conference Paper
Background: Response to anti-programmed death 1/programmed death ligand 1 (D-L1) therapy is associated with tumor expression of D-L1 and an 18-gene T-cell-inflamed gene expression profile (GE) across several tumor types. The association and utility of the GE, as calculated using baseline RNA-seq data as a predictor of pembrolizumab response, was ev...
Conference Paper
Background: Response to anti-programmed death 1/programmed death ligand 1 (D-L1) therapy is associated with tumor expression of D-L1 and an 18-gene T-cell-inflamed gene expression profile (GE) across several tumor types. The association and utility of the GE, as calculated using baseline RNA-seq data as a predictor of pembrolizumab response, was ev...
Conference Paper
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor prognosis when metastatic. Immunotherapy, especially in combination with taxane chemotherapy has recently been shown to improve outcomes with PD-L1 as predictive biomarker for survival. To understand the mechanisms of response/resistance to chemo-immunotherapy...
Article
Background Growing evidence suggests that the tumor immune microenvironment influences breast cancer development and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer is correlated with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcin...
Article
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Imiquimod is a topical toll-like-receptor-7 agonist currently used for treating basal cell carcinoma. Recently, imiquimod has demonstrated tumor regression in melanoma and breast cancer skin metastases. However, the molecular perturbations induced by imiquimod in breast cancer metastases have not been previously characterized. Here, we describe tra...
Article
1067 Background: In the IMpassion130 study in 1L mTNBC (N = 902), PFS with atezo + nP was significantly better than with placebo (P) + nP in ITT (HR, 0.80) and PD-L1 IC+ (HR, 0.62) patients (pts). Clinically meaningful OS improvement (HR, 0.62) was also seen in PD-L1+ pts. PROs were used to document pt perspectives on overall clinical benefit of at...
Article
1068 Background: IMpassion130 showed PFS benefit with A + nP vs placebo (P) + nP as 1L tx for mTNBC in the ITT and PD-L1 IC+ pts. We report expanded safety data with 4.5-mo longer follow-up (FU), focusing on adverse events of special interest (AESI), potentially immune related. Methods: Pts with unresectable locally advanced or mTNBC received nP 10...
Article
1003 Background: IMpassion130 evaluated atezo (anti–PD-L1) + nP vs placebo + nP in 1L mTNBC. The primary PFS analysis found that atezo + nP significantly improved PFS in intent-to-treat (ITT) and PD-L1+ pts vs placebo + nP, with efficacy driven by the PD-L1+ population. At that time, the 1st interim OS analysis was conducted (Schmid, NEJM 2018). He...
Article
TPS604 Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer with poor prognosis and is often resistant to neoadjuvant chemotherapy with risk of early recurrence and systemic spread of disease. PD-L1 expression in IBC is frequent (Bertucci et al. Oncotarget 2015), and blockade of the PD-1/PD-L1 axis with checkpoi...
Article
Breast oncologists are intimately familiar with managing treatment-related adverse events of endocrine, cytotoxic and targeted therapies, but the approval of immune-checkpoint inhibitors (ICIs) for metastatic triple-negative breast cancer (TNBC) poses new challenges. Herein, we discuss the safety of ICIs in metastatic TNBC, with an emphasis on immu...
Article
In Reply In our article,¹ we reported on the phase 1b cohort of patients with advanced/metastatic triple-negative breast cancer (mTNBC) treated with the immune checkpoint inhibitor (ICI) atezolizumab combined with chemotherapy. Li et al inquired about the hypothyroidism incidence in this study, noting the 17% frequency reported in the IMpassion130...
Article
Importance There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing at the time of this narrative review. The objective of this review is to describe the current status of immunotherapy in breast cancer, highlighting its potential in both early-stage and metastatic disease...
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Purpose: The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC). Methods: Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified...
Article
Metaplastic breast cancer (MPBC) is a rare subtype that accounts for <1% of all breast cancers. Although these are typically “triple negative,” they are relatively chemotherapy-refractory compared to conventional triple negative invasive breast cancers with more aggressive features and an overall poor prognosis. MPBC is a heterogeneous group of tum...
Article
Background Unresectable locally advanced or metastatic triple-negative (hormone-receptor–negative and human epidermal growth factor receptor 2 [HER2]–negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)–paclitaxel may enhance the anticancer activity of atezolizumab. Methods In this phase 3 trial, we...
Article
Importance The humanized monoclonal antibody atezolizumab targets programmed death-ligand 1 and has demonstrated durable single-agent activity in a subset of metastatic triple-negative breast cancers. To extend the observed activity, combinatorial approaches are being tested with standard cytotoxic chemotherapies known to induce immunogenic tumor c...
Article
Immune-checkpoint blockade (ICB), in particular PD-1 inhibition, has rapidly changed the treatment landscape and altered therapeutic paradigms across many tumor types, with unprecedented rates of durable clinical responses in a number of cancers. Despite this success, only a subset of patients responds to ICB and, as a result, predictive biomarkers...
Article
The immune system encompasses a broad array of defense mechanisms against foreign threats, including invading pathogens and transformed neoplastic cells. Toll-like receptors (TLRs) are critically involved in innate immunity, serving as pattern recognition receptors whose stimulation leads to additional innate and adaptive immune responses. Malignan...
Article
Triple negative breast cancer (TNBC) is a heterogeneous disease that comprises 15-20% of all breast cancers and is more frequently seen in younger women, African-Americans, and BRCA1 expression. Advanced TNBC carries aggressive features and is associated with overall poor outcomes. Unfortunately, there are no targeted therapies available for non-BR...
Article
Background: Recent data support the use of post-mastectomy radiation therapy (PMRT) in women with one to three positive lymph nodes; however, the benefit of PMRT in patients with micrometastatic nodal disease (N1mi) is unknown. We evaluated the survival impact of PMRT in patients with N1mi within the National Cancer Database. Methods: The patter...
Article
Environmental nutrient levels impact cancer cell metabolism, resulting in context-dependent gene essentiality. Here, using RNAi-based loss of function screening, we identify environmental oxygen level as a major driver of differential essentiality between in vitro model systems and in vivo tumours. Above the 3-8% oxygen concentration typical of mos...
Article
Introduction: Outcomes for patients (pts) with mTNBC remain poor, with chemotherapy as a historic mainstay treatment. Atezo (anti-PD-L1) demonstrated single-agent activity in mTNBC, and initial data suggested the addition of chemotherapy was safe with encouraging activity (Adams, 2016). Here we report long-term outcomes, with OS, for atezo + nab-pa...
Article
The matrix metalloproteinases (MMP) are a family of proteolytic enzymes that degrade multiple components of the extracellular matrix. A large body of experimental and clinical evidence has implicated MMPs in tumor invasion, neoangiogenesis, and metastasis, and therefore they represent ideal pharmacologic targets for cancer therapy. From the 1990s t...
Article
Purpose: This study examined the feasibility, efficacy (abscopal effect) and immune effects of TGFβ blockade during radiotherapy in metastatic breast cancer patients. Experimental design: Prospective randomized trial comparing two doses of TGFβ blocking antibody fresolimumab. Metastatic breast cancer patients with at least three distinct metasta...
Article
Advances in cancer immunotherapy and a growing body of research have focused on the role of the antitumor response in breast cancer. Triple-negative breast cancer (TNBC) is the most immunogenic breast cancer subtype, and there is strong evidence that tumor-infiltrating lymphocytes in TNBC have prognostic value and are associated with clinical outco...
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Background and purpose: Resistance to endocrine therapies in hormone receptor (HR)-positive breast cancer is a significant challenge. Prior studies have shown that low-dose oral cyclophosphamide can transiently deplete regulatory T cells (Tregs) and improve anti-tumor immunity. We investigated the combination of exemestane with cyclophosphamide in...