Daniel F Hayes

Concordia University–Ann Arbor, Ann Arbor, Michigan, United States

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Publications (373)3618.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiomyopathy is a known complication of anthracycline-based adjuvant chemotherapy and is more commonly reported in population-based studies of breast cancer survivors than in clinical trials. This study prospectively evaluated the prevalence of elevated cardiac biomarkers in unselected patients who had been treated with doxorubicin for early-stage breast cancer and the prevalence of reduced LVEF in patients with an elevated biomarker. All participants underwent an examination, symptom inventory, medical record review, and biomarker analysis for BNP, troponin, and plasma and urine NT-proBNP. Patients who had one or more elevated biomarkers were referred for echocardiogram; systolic dysfunction was defined as LVEF less than 55 %. Multivariable logistic regression was used to determine the associations between age, BMI, cumulative dose of doxorubicin, diabetes, hypertension, and left-sided radiation therapy and the risk of reduced LVEF. Among the 269 patients who underwent lab testing (mean age 56 years, mean time since completion of doxorubicin-based chemotherapy 6 years), 192 (72 %) had one or more elevated biomarker. Among the 166 patients who completed an echocardiogram, 11.5 % had a LVEF < 55 %. After adjusting for covariates known to affect cardiac function, multivariable logistic regression revealed plasma NT-proBNP to be the only measured cardiac biomarker associated with systolic dysfunction. There is a relationship between NT-proBNP and the frequency of reduced LVEF in women treated with doxorubicin for curative intent; further study of NT-proBNP as a potential biomarker for subclinical cardiac dysfunction after exposure to anthracyclines is warranted.
    Breast Cancer Research and Treatment 06/2015; DOI:10.1007/s10549-015-3454-8 · 4.20 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P6-08-50-P6-08-50. DOI:10.1158/1538-7445.SABCS14-P6-08-50 · 9.28 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P6-03-08-P6-03-08. DOI:10.1158/1538-7445.SABCS14-P6-03-08 · 9.28 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):OT2-1-01-OT2-1-01. DOI:10.1158/1538-7445.SABCS14-OT2-1-01 · 9.28 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P3-11-16-P3-11-16. DOI:10.1158/1538-7445.SABCS14-P3-11-16 · 9.28 Impact Factor
  • Daniel F Hayes, Anne F Schott
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    ABSTRACT: Neoadjuvant chemotherapy has several appealing potential benefits compared with classic adjuvant chemotherapy. Of these, the only proven benefit is to facilitate the surgical approach, either by converting an inoperable cancer to one that is operable, or by converting a patient who is felt to be a candidate for mastectomy to one who might be treated successfully with breast conserving therapy. Randomized trials comparing neoadjuvant chemotherapy with postoperative chemotherapy have failed to demonstrate prolongation of overall survival. The benefits of monitoring apparent response during neoadjuvant chemotherapy have not been proven. Conduct of phase II drug development trials in the neoadjuvant setting may be advantageous compared with performing such trials in the metastatic setting. However, such trials raise concerns that are not unavoidable but need to be addressed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    JNCI Monographs 05/2015; 2015(51):36-9. DOI:10.1093/jncimonographs/lgv004
  • Anne F Schott, Charles M Perou, Daniel F Hayes
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    ABSTRACT: This is an exciting time to be in cancer medicine. New technologies, such as next-generation sequencing (NGS), have increased our understanding of the molecular aberrations that define cancer. This, in turn, has led to the identification of cancer-specific molecular targets and potential drugs to confront these targets. As these new technologies move toward clinical application, a new vocabulary of "genome medicine" has been introduced to the field of oncology. Unfortunately, unclear or incorrect use of the new terminology has led to semantic misunderstandings that impair communication between the basic research and clinical practice arenas. These misunderstandings have led to assumptions regarding the clinical application of NGS and other technologies that may or may not be true. For example, some organizations that perform NGS testing on clinical samples have endorsed use of the results of such tests to direct specific therapies based on laboratory hypotheses, but without clinical testing of the hypotheses to show utility for these potential predictive claims. Here, we review some simple, and hopefully universally acceptable, definitions, concepts, and trial designs so that laboratory researchers and clinicians can move closer toward speaking the same language. Cancer Res; 75(10); 1-6. ©2015 AACR. ©2015 American Association for Cancer Research.
    Cancer Research 04/2015; 75(10). DOI:10.1158/0008-5472.CAN-15-0174 · 9.28 Impact Factor
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    ABSTRACT: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. In this review, we discuss the key steps in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before initiation of the study. Application of the methodology outlined above should result in a more efficient and effective approach to the development of cancer biomarkers as well as the reporting of cancer biomarker studies. With rigorous application, all stakeholders, and especially patients, would be expected to benefit. © 2015 American Association for Clinical Chemistry.
    Clinical Chemistry 04/2015; 61(6). DOI:10.1373/clinchem.2015.239863 · 7.77 Impact Factor
  • Journal of Clinical Oncology 04/2015; 33(14). DOI:10.1200/JCO.2014.60.5519 · 17.88 Impact Factor
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    ABSTRACT: Circulating Tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). We tested whether EpCAM based capture system (CellSearch®) is effective in patients with triple negative (TN) MBC, and whether CTC-apoptosis and clustering enhances the prognostic role of CTC. CTC enumeration and apoptosis was determined using the CXC CellSearch® kit at baseline and days 15 and 29 in blood drawn from TN MBC patients who participated in a prospective randomized phase II trial of nanoparticle albumin-bound paclitaxel (nab-PAC) with or without tigatuzumab (TIG). Association between levels of CTC and patient outcomes was assessed using logistic regression, Kaplan Meier curves, and Cox proportional hazards modeling. Nineteen of 52 (36.5%), 14/52 (26.9%), and 13/49 (26.5%) patients who were evaluable had elevated CTC (≥5CTC/7.5 ml WB) at baseline, days 15 and 29, respectively. Patients with elevated vs. not elevated CTC at each time point had worse progression free survival (PFS) (p=0.005, 0.0003, 0.0002, respectively). The odds of clinical benefit response for those who had elevated vs. low CTC at baseline and days 15 and 29 were 0.25 (95% CI: 0.08-0.84, p=0.024), 0.19 (95% CI: 0.05-0.17, p=0.014), and 0.06 (95% CI: 0.01-0.33, p=0.001), respectively. There was no apparent prognostic effect comparing CTC-apoptosis vs. non-apoptosis. Presence of CTC-cluster at day 15, and day 29 was associated with shorter PFS. CTC were detected using CellSearch® assay in approximately one-third of TN MBC patients. Elevated CTC at baseline and days 15 and 29 were prognostic, and reductions in CTC levels reflected response. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 03/2015; DOI:10.1158/1078-0432.CCR-14-2781 · 8.19 Impact Factor
  • Journal of Clinical Oncology 03/2015; 33(11). DOI:10.1200/JCO.2014.59.7559 · 17.88 Impact Factor
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    ABSTRACT: Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference <0.6 and Maximum Absolute Deviation from reference <1.0 (log2-transformed data). Prespecified success criteria for tissue microarray scoring required intraclass correlation significantly >0.70 but aiming for observed intraclass correlation ≥0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95% credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.Modern Pathology advance online publication, 20 February 2015; doi:10.1038/modpathol.2015.38.
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    ABSTRACT: Purpose: Endocrine therapy (ET) fails to induce a response in one-half of patients with hormone receptor (HR) positive metastatic breast cancer (MBC) and almost all will eventually become refractory to ET. Circulating Tumor Cells (CTC) are associated with worse prognosis in MBC patients, but enumeration alone is insufficient to predict the absolute odds of benefit from any therapy, including ET. We developed a multi-parameter CTC-Endocrine Therapy Index (CTC-ETI), which we hypothesize may predict resistance to ET in patients with HR positive MBC. Experimental Design: The CTC-ETI combines enumeration and CTC expression of four markers: estrogen receptor (ER), B-cell lymphoma 2 (BCL-2), Human Epidermal Growth Factor Receptor 2 (HER2), and Ki67. The CellSearch® System and reagents were used to capture CTC and measure protein expression by immunofluorescent staining on CTC. Results: The feasibility of determining CTC-ETI was initially established in vitro and then in a prospective single-institution pilot study in MBC patients. CTC-ETI was successfully determined in 44/50 (88%) patients. Eighteen (41%), 9 (20%), and 17 (39%) patients had low, intermediate, and high CTC-ETI scores, respectively. Inter-observer concordance of CTC-ETI determination was 94-95% (Kappa statistic 0.90-0.91). Inter- and cell-to-cell intra-patient heterogeneity of expression of each of the CTC-markers was observed. CTC biomarker expression was discordant from both primary and metastatic tissue. Conclusions: CTC expression of ER, BCL-2, HER2, and Ki67 can be reproducibly measured with high analytical validity using the CellSearch® System. The clinical implications of CTC-ETI, and of the heterogeneity of CTC-biomarker expression, are being evaluated in an ongoing prospective trial.
    Clinical Cancer Research 11/2014; 21(11). DOI:10.1158/1078-0432.CCR-14-1913 · 8.19 Impact Factor
  • Daniel F Hayes
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    ABSTRACT: A tumor biomarker is a molecular or process-based change that reflects the status of an underlying malignancy. A tumor biomarker may be identified and measured by one or more assays, or tests, for the biomarker. Increasingly, tumor biomarker tests are being used to drive patient management, either by identifying patients who do not require any, or any further, treatment, or by identifying patients whose tumors are so unlikely to respond to a given type of treatment that it will cause more harm than good. A tumor biomarker assay should only be used to guide management if it has analytical validity, meaning that it is accurate, reproducible, and reliable, and if it has been shown to have clinical utility. The latter implies that high levels of evidence are available that demonstrate that application of the tumor biomarker test for a given use context results in better outcomes, or similar outcomes with less cost, than if the assay were not applied. Use contexts include risk categorization, screening, differential diagnosis, prognosis, prediction of therapeutic activity or monitoring disease course. Very few tumor biomarker tests have passed these high bars for routine clinical application. However, if tumor biomarker tests are going to be used to drive patient care, than an understanding, and careful assessment, of these concepts are essential, since "A Bad Tumor Biomarker Test Is as Bad as a Bad Drug." Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
    Molecular Oncology 10/2014; 9(5). DOI:10.1016/j.molonc.2014.10.004 · 5.94 Impact Factor
  • N Lynn Henry, Anne F Schott, Daniel F Hayes
    Journal of Clinical Oncology 09/2014; 32(29). DOI:10.1200/JCO.2014.57.6132 · 17.88 Impact Factor
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    ABSTRACT: The aim of this study is to use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. Patients treated with (n = 28) or without chemotherapy (n = 37) and healthy controls (n = 32) were scanned coincident with pre- and one-month post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response, characterized by higher spatial variance in executive network activity, than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction.
    Breast Cancer Research and Treatment 08/2014; 147(2). DOI:10.1007/s10549-014-3092-6 · 4.20 Impact Factor
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    ABSTRACT: BACKGROUND Aromatase inhibitor (AI) therapy results in substantial survival benefits for patients with hormone receptor-positive breast cancer. The rates of poor adherence and discontinuation of AI therapy are high, primarily because of treatment-related toxicities like musculoskeletal pain. Although pain-related symptoms may worsen during AI therapy, the authors hypothesized that nonpersistence with AI therapy was associated with symptoms that were present before treatment initiation.METHODS Postmenopausal women initiating AI therapy who were enrolled in a prospective clinical trial completed questionnaires at baseline to assess sleep, fatigue, mood, and pain. Reasons for treatment discontinuation during the first year of treatment were recorded. Associations between baseline patient-reported symptoms and treatment discontinuation because of toxicity were identified using logistic regression.RESULTSFour hundred forty-nine patients were evaluable. The odds of treatment discontinuation were higher in patients who reported a greater number of symptoms before AI initiation. Baseline poor sleep quality was associated with early treatment discontinuation, with an odds ratio (OR) of 1.91 (95% confidence interval [CI], 1.26-2.89; P = .002). Baseline presence of tired feeling and forgetfulness had similar ORs for discontinuation (tired feeling: OR, 1.76; 95% CI, 1.15-2.67; P = .009; forgetfulness: OR, 1.66; 95% CI, 1.11-2.48; P = .015). An increasing total number of baseline symptoms was associated with an increased likelihood of treatment discontinuation, with an OR of 1.89 (95% CI, 1.20-2.96; P = .006) for 3 to 5 symptoms versus 0 to 2 symptoms.CONCLUSIONS Symptom clusters in breast cancer survivors that are present before the initiation of adjuvant AI therapy may have a negative impact on a patient's persistence with therapy. Interventions to manage these symptoms may improve breast cancer outcomes and quality of life. Cancer 2014. © 2014 American Cancer Society.
    Cancer 08/2014; 120(16). DOI:10.1002/cncr.28756 · 4.90 Impact Factor
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    ABSTRACT: Purpose Increased circulating tumor cells (CTCs; five or more CTCs per 7.5 mL of whole blood) are associated with poor prognosis in metastatic breast cancer (MBC). A randomized trial of patients with persistent increase in CTCs tested whether changing chemotherapy after one cycle of first-line chemotherapy would improve the primary outcome of overall survival (OS). Patients and Methods Patients with MBC who did not have increased CTCs at baseline remained on initial therapy until progression (arm A). Patients with initially increased CTCs that decreased after 21 days of therapy remained on initial therapy (arm B). Patients with persistently increased CTCs after 21 days of therapy were randomly assigned to continue initial therapy (arm C1) or change to an alternative chemotherapy (arm C2). Results Of 595 eligible and evaluable patients, 276 (46%) did not have increased CTCs (arm A). Of those with initially increased CTCs, 31 (10%) were not retested, 165 were assigned to arm B, and 123 were randomly assigned to arm C1 or C2. No difference in median OS was observed between arm C1 and C2 (10.7 and 12.5 months, respectively; P = .98). CTCs were strongly prognostic. Median OS for arms A, B, and C (C1 and C2 combined) were 35 months, 23 months, and 13 months, respectively (P < .001). Conclusion This study confirms the prognostic significance of CTCs in patients with MBC receiving first-line chemotherapy. For patients with persistently increased CTCs after 21 days of first-line chemotherapy, early switching to an alternate cytotoxic therapy was not effective in prolonging OS. For this population, there is a need for more effective treatment than standard chemotherapy. (C) 2014 by American Society of Clinical Oncology
    Journal of Clinical Oncology 06/2014; 32(31). DOI:10.1200/JCO.2014.56.2561 · 17.88 Impact Factor
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    Journal of Clinical Oncology 04/2014; DOI:10.1200/JCO.2014.55.0673 · 17.88 Impact Factor
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    ABSTRACT: Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. The NCCN Guidelines specific to management of large clinical stage II and III tumors are discussed in this article. These guidelines are the work of the members of the NCCN Breast Cancer Panel. Expert medical clinical judgment is required to apply these guidelines in the context of an individual patient to provide optimal care. Although not stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer.
    Journal of the National Comprehensive Cancer Network: JNCCN 04/2014; 12(4):542-90. · 4.24 Impact Factor

Publication Stats

22k Citations
3,618.82 Total Impact Points


  • 2001–2015
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • Washington DC VA Medical Center
      Washington, Washington, D.C., United States
  • 2003–2014
    • University of Michigan
      • • Department of Internal Medicine
      • • Division of Hematology and Oncology
      Ann Arbor, Michigan, United States
  • 2012
    • American Society of Clinical Oncology
      Alexandria, Virginia, United States
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
  • 2010
    • University of Utah
      Salt Lake City, Utah, United States
  • 2004–2010
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, Indiana, United States
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 2009
    • Loyola University Medical Center
      Maywood, Illinois, United States
    • National Cancer Institute (USA)
      • Biometrics Research Branch
      Maryland, United States
    • Brigham and Women's Hospital
      • Department of Pathology
      Boston, MA, United States
  • 2007
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Duke University
      Durham, North Carolina, United States
    • Fred Hutchinson Cancer Research Center
      Seattle, Washington, United States
  • 2002–2007
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
  • 1998–2007
    • Georgetown University
      • Lombardi Cancer Center
      Washington, Washington, D.C., United States
  • 2006
    • Johns Hopkins Medicine
      • Department of Medicine
      Baltimore, Maryland, United States
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 2005
    • Stanford Medicine
      • Stanford Emergency Department (Hospitals and Clinics)
      Stanford, California, United States
    • University of North Carolina at Chapel Hill
      • Lineberger Comprehensive Cancer Center
      Chapel Hill, NC, United States
  • 2000
    • Roswell Park Cancer Institute
      Buffalo, New York, United States
  • 1986–1999
    • Dana-Farber Cancer Institute
      • • Department of Radiation Oncology
      • • Lank Center for Genitourinary Oncology
      Boston, Massachusetts, United States
  • 1996
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States
  • 1990–1993
    • Harvard Medical School
      • • Department of Pathology
      • • Department of Radiation Oncology
      Boston, Massachusetts, United States
  • 1987
    • University of Massachusetts Boston
      Boston, Massachusetts, United States