Publications by authors named "Frederick Howard"

Background: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have improved the efficacy of endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) and are now used in both early-stage and metastatic disease. Recent case reports suggest that pseudo-serum creatinine (Scr) elevations are likely a class effect of CDK4/6i.

Methods: This single-center retrospective analysis included patients aged ≥18 years who received at least one dose of palbociclib, ribociclib, or abemaciclib for the treatment of HR+/HER2- BC in the early or advanced setting.

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Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of molecular features. These approaches distill cancer histologic images into high-level features, which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom generative adversarial network-HistoXGAN-capable of reconstructing representative histology using feature vectors produced by common feature extractors.

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Background: For patients with breast cancer undergoing neoadjuvant chemotherapy (NACT), most of the existing prediction models of pathologic complete response (pCR) using clinicopathological features were based on standard statistical models like logistic regression, while models based on machine learning mostly utilized imaging data and/or gene expression data. This study aims to develop a robust and accessible machine learning model to predict pCR using clinicopathological features alone, which can be used to facilitate clinical decision-making in diverse settings.

Methods: The model was developed and validated within the National Cancer Data Base (NCDB, 2018-2020) and an external cohort at the University of Chicago (2010-2020).

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Article Synopsis
  • The CREATE-X trial showed that adjuvant capecitabine can improve survival for high-risk triple-negative breast cancer patients, but the standard dose is often hard to tolerate for many in the US.
  • A retrospective study at the University of Chicago Medicine evaluated the safety and tolerability of capecitabine in 67 TNBC patients, looking specifically at their relative dose intensity (RDI) and side effects over eight treatment cycles.
  • Results indicated that the average RDI was significantly lower than in the CREATE-X trial, with hand-foot syndrome, diarrhea, and fatigue being the most common side effects; the study found no major differences in tolerability based on age, race, BMI, or initial dosage.
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In this era of precision medicine, incorporating quantitative measures of estrogen receptor (ER)/progesterone receptor (PR)/Ki-67 expressions and genomic assays could more precisely identify neoadjuvant systemic therapy with the highest likelihood of response and tumor downstaging. In our recent study, we quantified the likelihood of achieving breast-conserving surgery (BCS vs. mastectomy) after neoadjuvant chemotherapy or endocrine therapy as a function of demographics, quantitative ER/PR/Ki-67 expressions, 21-gene recurrence scores, or 70-gene risk scores in early-stage, hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

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Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer.

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Background: Given increased neoadjuvant therapy use in early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer, we sought to quantify likelihood of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) or endocrine therapy (NET) as a function of ER%/PR%/Ki-67%, 21-gene recurrence scores (RS), or 70-gene risk groups.

Methods: We analyzed the 2010-2020 National Cancer Database. Surgery was categorized as "mastectomy/BCS.

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Background: Deployment and access to state-of-the-art precision medicine technologies remains a fundamental challenge in providing equitable global cancer care in low-resource settings. The expansion of digital pathology in recent years and its potential interface with diagnostic artificial intelligence algorithms provides an opportunity to democratize access to personalized medicine. Current digital pathology workstations, however, cost thousands to hundreds of thousands of dollars.

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Background: Since the COVID-19 pandemic began, we have seen rapid growth in telemedicine use. However, telehealth care and services are not equally distributed, and not all patients with breast cancer have equal access across US regions. There are notable gaps in existing literature regarding the influence of neighborhood-level socioeconomic status on telemedicine use in patients with breast cancer and oncology services offered through telehealth versus in-person visits.

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Background: The use of large language models (LLM) has recently gained popularity in diverse areas, including answering questions posted by patients as well as medical professionals.

Objective: To evaluate the performance and limitations of LLMs in providing the correct diagnosis for a complex clinical case.

Design: Seventy-five consecutive clinical cases were selected from the Massachusetts General Hospital Case Records, and differential diagnoses were generated by OpenAI's GPT3.

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Given high costs of Oncotype DX (ODX) testing, widely used in recurrence risk assessment for early-stage breast cancer, studies have predicted ODX using quantitative clinicopathologic variables. However, such models have incorporated only small cohorts. Using a cohort of patients from the National Cancer Database (NCDB, n = 53,346), we trained machine learning models to predict low-risk (0-25) or high-risk (26-100) ODX using quantitative estrogen receptor (ER)/progesterone receptor (PR)/Ki-67 status, quantitative ER/PR status alone, and no quantitative features.

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Purpose: Artificial intelligence (AI) models can generate scientific abstracts that are difficult to distinguish from the work of human authors. The use of AI in scientific writing and performance of AI detection tools are poorly characterized.

Methods: We extracted text from published scientific abstracts from the ASCO 2021-2023 Annual Meetings.

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Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of novel molecular features. These approaches distill cancer histologic images into high-level features which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom generative adversarial network - HistoXGAN - capable of reconstructing representative histology using feature vectors produced by common feature extractors.

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Article Synopsis
  • Deep learning methods are becoming essential for analyzing histopathological images, but many existing approaches are limited to specific domains and tools, with few open-source options available for interactive use.
  • Slideflow is a newly developed, flexible deep learning library designed specifically for digital pathology, providing various methods and a fast interface for deploying trained models.
  • With features like efficient stain normalization, weakly-supervised classification, and rapid whole-slide image processing, Slideflow allows researchers to experiment easily with different deep learning methods using Tensorflow or PyTorch on various devices, including Raspberry Pi.
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Background: Guidelines recommend the use of genomic assays such as OncotypeDx to aid in decisions regarding the use of chemotherapy for hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer. The RSClin prognostic tool integrates OncotypeDx and clinicopathologic features to predict distant recurrence and chemotherapy benefit, but further validation is needed before broad clinical adoption.

Methods: This study included patients from the National Cancer Data Base (NCDB) who were diagnosed with stage I-III HR+/HER2- breast cancer from 2010 to 2020 and received adjuvant endocrine therapy with or without chemotherapy.

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Purpose: To externally evaluate a mammography-based deep learning (DL) model (Mirai) in a high-risk racially diverse population and compare its performance with other mammographic measures.

Materials And Methods: A total of 6435 screening mammograms in 2096 female patients (median age, 56.4 years ± 11.

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Purpose: To assess whether measurement of the bilateral asymmetry of semiquantitative and quantitative perfusion parameters from ultrafast dynamic contrast-enhanced MRI (DCE-MRI), allows early prediction of pathologic response after neoadjuvant chemotherapy (NAC) in patients with HER2+ breast cancer.

Materials And Methods: Twenty-eight female patients with HER2+ breast cancer treated with NAC who underwent pre-NAC ultrafast DCE-MRI (3-9 s/phase) were enrolled for this study. Four semiquantitative and two quantitative parenchymal parameters were calculated for each patient.

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Article Synopsis
  • Artificial intelligence, particularly deep neural networks (DNN), can classify tumors from histology samples quickly and accurately, often matching or surpassing human pathologists' abilities.
  • There is a challenge in understanding how these neural networks make their predictions, but new explainability tools are being developed, including the use of synthetic histology created by conditional generative adversarial networks (cGAN).
  • The synthetic histology not only helps visualize key histologic features linked to tumor molecular types but also enhances the training of pathologists by providing intuitive visual aids for better understanding tumor biology.
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Background: Endocrine-resistant HR+/HER2- breast cancer (BC) and triple-negative BC (TNBC) are of interest for molecularly informed treatment due to their aggressive natures and limited treatment profiles. Patients of African Ancestry (AA) experience higher rates of TNBC and mortality than European Ancestry (EA) patients, despite lower overall BC incidence. Here, we compare the molecular landscapes of AA and EA patients with HR+/HER2- BC and TNBC in a real-world cohort to promote equity in precision oncology by illuminating the heterogeneity of potentially druggable genomic and transcriptomic pathways.

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OncotypeDX and MammaPrint assays have not been validated to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in early-stage breast cancer patients. We analyzed the 2010-2019 National Cancer Database and found that high OncotypeDX recurrence scores or high MammaPrint scores were associated with greater odds of pCR. Our findings suggest that OncotypeDX and MammaPrint testing predict pCR after NACT and could facilitate clinical decision-making between clinicians and patients.

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Purpose: There are a paucity of data and a pressing need to evaluate response to neoadjuvant chemotherapy (NACT) and determine long-term outcomes in young Black women with early-stage breast cancer (EBC).

Methods: We analyzed data from 2196 Black and White women with EBC treated at the University of Chicago over the last 2 decades. Patients were divided into groups based on race and age at diagnosis: Black women [Formula: see text] 40 years, White women [Formula: see text] 40 years, Black women [Formula: see text] 55 years, and White women [Formula: see text] 55 years.

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Large language models such as ChatGPT can produce increasingly realistic text, with unknown information on the accuracy and integrity of using these models in scientific writing. We gathered fifth research abstracts from five high-impact factor medical journals and asked ChatGPT to generate research abstracts based on their titles and journals. Most generated abstracts were detected using an AI output detector, 'GPT-2 Output Detector', with % 'fake' scores (higher meaning more likely to be generated) of median [interquartile range] of 99.

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Gene expression-based recurrence assays are strongly recommended to guide the use of chemotherapy in hormone receptor-positive, HER2-negative breast cancer, but such testing is expensive, can contribute to delays in care, and may not be available in low-resource settings. Here, we describe the training and independent validation of a deep learning model that predicts recurrence assay result and risk of recurrence using both digital histology and clinical risk factors. We demonstrate that this approach outperforms an established clinical nomogram (area under the receiver operating characteristic curve of 0.

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Importance: Among patients with breast cancer, inconsistent findings have been published on racial disparities in achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT).

Objective: To investigate whether racial disparities exist in achieving pCR and what factors contribute to them.

Design, Setting, And Participants: Within the ongoing Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), which consists of a prospectively ascertained cohort of patients with breast cancer, 690 patients with stage I to III breast cancer receiving NACT were identified for this single-institution study at the University of Chicago Medicine.

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