Publications by authors named "Mankoff D"

The ternary complex of PGRMC1-σ2R/TMEM97-LDLR has recently been discovered and plays a role in cholesterol transport. This study investigated whether individual components of that complex are prognostic breast cancer biomarkers and defined expression in established molecular subtypes. 4,463 invasive breast cancers were analyzed as a function of molecular and phenotypic markers, estimates of cellular proliferation, and recurrence-free survival.

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Poly(adenosine diphosphate-ribose) polymerase-1 (PARP1) inhibitors have improved ovarian cancer treatment outcomes. However, clinical response remains heterogeneous. Existing biomarkers, mainly breast cancer susceptibility genes 1 and 2 (), are suboptimal.

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The poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have demonstrated efficacy in ovarian, breast, and prostate cancers, but current biomarkers do not consistently predict clinical benefit. F-fluorthanatrace (F-FTT) is an analog to rucaparib, a clinically approved PARPi, and is a candidate biomarker for PARPi response. This study intends to characterize F-FTT pharmacokinetics in breast cancer and optimize image timing for clinical trials.

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As molecular imaging use expands for patients with breast cancer, it is important for breast radiologists to have a basic understanding of molecular imaging, including PET. Although breast radiologists may not directly interpret such studies, basic knowledge of molecular imaging will enable the radiologist to better direct diagnostic workup of patients as well as discuss diagnostic imaging with the patient and other treating physicians. Several new tracers are now available to complement imaging glucose metabolism with FDG.

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Article Synopsis
  • - A 78-year-old woman with invasive lobular breast cancer and left axillary node metastasis underwent 18 F-fluoroestradiol (FES) PET/CT for evaluation of right axillary lymph nodes previously seen on another imaging scan.
  • - The 18 F-FES PET/CT imaging detected abnormal nodes in the right axilla and cervical region, which were confirmed as metastases through biopsy, resulting in the patient's cancer being upstaged from stage II to IV.
  • - This case highlights the effectiveness of 18 F-FES PET/CT in accurately staging metastatic invasive lobular carcinoma, aligning with guidelines that suggest its use in such evaluations.
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F-16α-Fluoroestradiol (F-FES) is a radiolabeled estrogen analogue positron emission tomography (PET) imaging agent that binds to the estrogen receptor (ER) in the nucleus of ER-expressing cells. Proof-of-concept studies of F-FES demonstrated expected correlation between tumoral F-FES-positivity on PET-imaging and ER+ status assessed on biopsy samples by radioligand binding and immunohistochemistry. After decades of study, F-FES PET/CT gained clinical approval in 2016 in France and 2020 in the United States for use in patients with ER+ metastatic or recurrent breast cancer.

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Article Synopsis
  • Institutional radiation safety committees assess research protocols to weigh the benefits of patient outcomes against radiation risks, often leading to delays in approvals.
  • A study of 110 protocols at the University of Pennsylvania showed that only 23% received outright approval, with many requiring edits or more information, contributing to an average approval time of 80.1 days.
  • The findings suggest the need for improvements in the review process, such as creating standardized documentation and promoting prompt responses to stipulations to expedite approvals without sacrificing quality.
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Background: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases.

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Background: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients with bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[F]fluoro-D-glucose (F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases.

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The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis.

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The estrogen receptor (ER), a steroid hormone receptor important in female physiology, is a significant contributor to breast carcinogenesis and progression and, as such, is an important therapeutic target. Approximately 70% of breast cancers will express ER at presentation, and the determination of ER expression by tissue assay, usually by immunohistochemistry, is part of the standard of care for newly diagnosed breast cancer. ER expression is important in guiding the approach to treatment, especially with the increase in relevant systemic therapies.

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In triple-negative breast cancer (TNBC) that relies on catabolism of amino acid glutamine, glutaminase (GLS) converts glutamine to glutamate, which facilitates glutathione synthesis by mediating the enrichment of intracellular cystine via xCT antiporter activity. To overcome chemo resistant TNBC, we have tested a strategy of disrupting cellular redox balance by inhibition of GLS and xCT by CB839 and Erastin, respectively. Key findings of our study include: 1.

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Purpose: To investigate combined MRI and F-FDG PET for assessing breast tumor metabolism/perfusion mismatch and predicting pathological response and recurrence-free survival (RFS) in women treated for breast cancer.

Methods: Patients undergoing neoadjuvant chemotherapy (NAC) for locally-advanced breast cancer were imaged at three timepoints (pre, mid, and post-NAC), prior to surgery. Imaging included diffusion-weighted and dynamic contrast-enhanced (DCE-) MRI and quantitative F-FDG PET.

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Introduction: Right ventricular (RV) function is a major determinant of outcome in patients with precapillary pulmonary hypertension (PH). We studied the effect of ranolazine on RV function over 6 months using multi-modality imaging and biochemical markers in patients with precapillary PH (groups I, III, and IV) and RV dysfunction [CMR imaging ejection fraction (EF) < 45%] in a longitudinal, randomized, double-blinded, placebo-controlled, multicenter study of ranolazine treatment.

Methods: Enrolled patients were assessed using cardiac magnetic resonance (CMR) imaging, C-acetate and -F-FDG positron emission tomography (PET), and plasma metabolomic profiling, at baseline and at the end of treatment.

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Article Synopsis
  • [18F]fluoroestradiol (FES) PET is a government-approved imaging method that helps assess how well hormone therapy might work for patients.
  • FES positivity indicates that patients are likely to benefit from endocrine therapies, similar to results seen with immunohistochemistry (IHC).
  • Recent research showed that measuring tumor heterogeneity with FES can predict treatment success and track changes in estrogen receptor activity during and after treatment.
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PET imaging with 16α-F-fluoro-17β-fluoroestradiol (F-FES), a radiolabeled form of estradiol, allows whole-body, noninvasive evaluation of estrogen receptor (ER). F-FES is approved by the U.S.

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In the United States, breast cancer is the second leading cause of cancer death in all women and the leading cause of cancer death in Black women. The breast cancer receptor profile, assessed with immunohistochemical staining of tissue samples, allows prediction of outcomes and direction of patient treatment. Approximately 80% of newly diagnosed breast cancers are hormone receptor (HR) positive, which is defined as estrogen receptor (ER) and/or progesterone receptor (PR) positive.

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