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John  Heine

John Heine, PhD

Program: Cancer Epidemiology

Research Program: Cancer Epidemiology Program


  • Overview

    Traditional breast cancer risk factors and subject history merged with risk factors derived from mammograms may result in better treatment decisions.


    • Cancer Epidemiology
    • Cancer Chemoprevention Research Interest Group
    • Cancer Epidemiology Program
    • Cancer Imaging & Technology Center of Excellence

    Education & Training


    • University of South Florida, MS - Physics
    • University of South Florida, PhD - Engineering Science
  • Research Interest

    Dr. Heine’s current research blends imaging physics with statistical learning methods to address unresolved issues in epidemiology with an emphasis on breast cancer risk assessments. Mammographic breast density is a significant breast cancer risk factor, not used clinically due to measurement difficulties.  Dr. Heine has made significant inroads into developing methods of calibrating mammograms to adjust for the acquisition technique differences and developing automated measures of breast density  that show strong association with breast cancer.  In parallel, Dr Heine is developing novel methods of incorporating statistical learning techniques into epidemiology for improved risk modeling. The near term objective of this discipline fusion research is to develop an automated system for data collection and analysis to enable both population and individual level risk assessments at the breast clinics within Moffitt Cancer Center.

  • Participating Trials

    Clinical Trial 19209
    Combined Imaging and Blood Biomarkers for Breast Cancer Diagnosis
    Condition: Healthy Subjects
    Status: Open

    If you believe you are eligible for one of these trials or studies, please call
    813-745-6100 or toll-free 1-800-679-0775.

  • Publications

    • Yaghjyan L, Wang Z, Warner ET, Rosner B, Heine J, Tamimi RM. Reproductive factors related to childbearing and a novel automated mammographic measure, V. Cancer Epidemiol Biomarkers Prev. 2024 Mar. Pubmedid: 38497795.
    • Barnard ME, DuPré NC, Heine JJ, Fowler EE, Murthy DJ, Nelleke RL, Chan A, Warner ET, Tamimi RM. Reproductive risk factors for breast cancer and association with novel breast density measurements among Hispanic, Black, and White women. Breast Cancer Res Treat. 2024 Apr.204(2):309-325. Pubmedid: 38095811. Pmcid: PMC10948301.
    • Heine J, Fowler EEE, Weinfurtner RJ, Hume E, Tworoger SS. Breast density analysis of digital breast tomosynthesis. Sci Rep. 2023 Oct.13(1):18760. Pubmedid: 37907569. Pmcid: PMC10618274.
    • Heine J, Fowler EEE, Berglund A, Schell MJ, Eschrich S. Techniques to produce and evaluate realistic multivariate synthetic data. Sci Rep. 2023 Jul.13(1):12266. Pubmedid: 37507387. Pmcid: PMC10382509.
    • Heine J, Fowler EEE, Weinfurtner RJ, Hume E, Tworoger SS. Breast Density Analysis Using Digital Breast Tomosynthesis. bioRxiv. 2023 Feb. Pubmedid: 36824710. Pmcid: PMC9948963.
    • Liu Y, Chen H, Heine J, Lindstrom S, Turman C, Warner ET, Winham SJ, Vachon CM, Tamimi RM, Kraft P, Jiang X. A genome-wide association study of mammographic texture variation. Breast Cancer Res. 2022 Nov.24(1):76. Pubmedid: 36344993. Pmcid: PMC9639267.
    • Yaghjyan L, Smotherman C, Heine J, Colditz GA, Rosner B, Tamimi RM. Associations of Oral Contraceptives with Mammographic Breast Density in Premenopausal Women. Cancer Epidemiol Biomarkers Prev. 2022 Feb.31(2):436-442. Pubmedid: 34862209. Pmcid: PMC8825703.
    • Warner ET, Rice MS, Zeleznik OA, Fowler EE, Murthy D, Vachon CM, Bertrand KA, Rosner BA, Heine J, Tamimi RM. Automated percent mammographic density, mammographic texture variation, and risk of breast cancer: a nested case-control study. NPJ Breast Cancer. 2021 May.7(1):68. Pubmedid: 34059687. Pmcid: PMC8166859.
    • Heine J, Fowler E, Scott CG, Jensen MR, Shepherd J, Hruska CB, Winham SJ, Brandt KR, Wu FF, Norman AD, Pankratz VS, Miglioretti DL, Kerlikowske K, Vachon CM. Mammographic Variation Measures, Breast Density, and Breast Cancer Risk. Ajr Am J Roentgenol. 2021 Aug.217(2):326-335. Pubmedid: 34161135. Pmcid: PMC9009534.
    • Rustagi AS, Scott CG, Winham SJ, Brandt KR, Norman AD, Jensen MR, Shepherd JA, Hruska C, Heine JJ, Pankratz VS, Kerlikowske K, Vachon CM. Association of Daily Alcohol Intake, Volumetric Breast Density, and Breast Cancer Risk. JNCI Cancer Spectr. 2021 Apr.5(2). Pubmedid: 33733051. Pmcid: PMC7952225.
    • Fowler EE, Berglund A, Schell MJ, Sellers TA, Eschrich S, Heine J. Empirically-derived synthetic populations to mitigate small sample sizes. J Biomed Inform. 2020 May.105:103408. Pubmedid: 32173502. Pmcid: PMC7839232.
    • Oh H, Rice MS, Warner ET, Bertrand KA, Fowler E, Eliassen AH, Rosner BA, Heine J, Tamimi RM. Early-Life and Adult Anthropometrics in Relation to Mammographic Image Intensity Variation in the Nurses' Health Studies. Cancer Epidemiol Biomarkers Prev. 2020 Feb.29(2):343-351. Pubmedid: 31826913. Pmcid: PMC7007347.
    • Fowler EE, Smallwood A, Khan N, Miltich C, Drukteinis J, Sellers TA, Heine J. Calibrated Breast Density Measurements. Acad Radiol. 2019 Sep.26(9):1181-1190. Pubmedid: 30545682. Pmcid: PMC6557684.
    • Fowler EEE, Hathaway C, Tillman F, Weinfurtner R, Sellers TA, Heine J. Spatial Correlation and Breast Cancer Risk. Biomed Phys Eng Express. 2019 Jul.5(4). Pubmedid: 33304615. Pmcid: PMC7725237.
    • Fowler E, Smallwood A, Khan N, Kilpatrick K, Sellers TA, Heine J. Technical challenges in generalizing calibration techniques for breast density measurements. Med Phys. 2019 Feb.46(2):679-688. Pubmedid: 30525207. Pmcid: PMC6367025.
    • Engmann NJ, Scott C, Jensen MR, Winham SJ, Ma L, Brandt KR, Mahmoudzadeh A, Whaley DH, Hruska CB, Wu FF, Norman AD, Hiatt RA, Heine J, Shepherd J, Pankratz VS, Miglioretti DL, Kerlikowski K, Vachon CM. Longitudinal Changes in Volumetric Breast Density in Healthy Women across the Menopausal Transition. Cancer Epidemiol Biomarkers Prev. 2019 Aug.28(8):1324-1330. Pubmedid: 31186265. Pmcid: PMC6677580.
    • Engmann NJ, Scott CG, Jensen MR, Winham S, Miglioretti DL, Ma L, Brandt K, Mahmoudzadeh A, Whaley DH, Hruska C, Wu F, Norman AD, Hiatt RA, Heine J, Shepherd J, Pankratz VS, Vachon CM, Kerlikowske K. Combined effect of volumetric breast density and body mass index on breast cancer risk. Breast Cancer Res Treat. 2019 Aug.177(1):165-173. Pubmedid: 31129803. Pmcid: PMC6640105.
    • Liu Y, Wang H, Li Q, McGettigan MJ, Balagurunathan Y, Garcia AL, Thompson ZJ, Heine JJ, Ye Z, Gillies RJ, Schabath MB. Radiologic Features of Small Pulmonary Nodules and Lung Cancer Risk in the National Lung Screening Trial: A Nested Case-Control Study. Radiology. 2018 Jan.286(1):298-306. Pubmedid: 28837413. Pmcid: PMC5738292.
    • Fowler EEE, Smallwood A, Miltich C, Drukteinis J, Sellers TA, Heine JJ. Generalized breast density metrics. Phys Med Biol. 2018 Dec.64(1):015006. Pubmedid: 30523909. Pmcid: PMC7034052.
    • Engmann NJ, Scott C, Jensen MR, Ma L, Brandt KR, Mahmoudzadeh A, Malkov S, Whaley DH, Hruska C, Wu FF, Winham S, Miglioretti DL, Norman AD, Heine J, Shepherd J, Pankratz VS, Vachon CM, Kerlikowske K. Longitudinal Changes in Volumetric Breast Density with Tamoxifen and Aromatase Inhibitors. Cancer Epidemiol Biomarkers Prev. 2017 Jun.26(6):930-937. Pubmedid: 28148596. Pmcid: PMC5457346.
    • Brandt KR, Scott CG, Ma L, Mahmoudzadeh AP, Jensen MR, Whaley DH, Wu FF, Malkov S, Hruska CB, Norman AD, Heine J, Shepherd J, Pankratz VS, Kerlikowske K, Vachon CM. Comparison of Clinical and Automated Breast Density Measurements: Implications for Risk Prediction and Supplemental Screening. Radiology. 2016 Jun.279(3):710-719. Pubmedid: 26694052. Pmcid: PMC4886704.
    • Wang H, Schabath MB, Liu Y, Stringfield O, Balagurunathan Y, Heine JJ, Eschrich SA, Ye Z, Gillies RJ. Association Between Computed Tomographic Features and Kirsten Rat Sarcoma Viral Oncogene Mutations in Patients With Stage I Lung Adenocarcinoma and Their Prognostic Value. Clin Lung Cancer. 2016 Jul.17(4):271-278. Pubmedid: 26712103. Pmcid: PMC4887405.
    • Burton A, Byrnes G, Stone J, Tamimi RM, Heine J, Vachon C, Ozmen V, Pereira A, Garmendia ML, Scott C, Hipwell JH, Dickens C, Schüz J, Aribal ME, Bertrand K, Kwong A, Giles GG, Hopper J, Pérez Gómez B, Pollán M, Teo SH, Mariapun S, Taib NA, Lajous M, Lopez-Riduara R, Rice M, Romieu I, Flugelman AA, Ursin G, Qureshi S, Ma H, Lee E, Sirous R, Sirous M, Lee JW, Kim J, Salem D, Kamal R, Hartman M, Miao H, Chia KS, Nagata C, Vinayak S, Ndumia R, van Gils CH, Wanders JO, Peplonska B, Bukowska A, Allen S, Vinnicombe S, Moss S, Chiarelli AM, Linton L, Maskarinec G, Yaffe MJ, Boyd NF, Dos-Santos-Silva I, McCormack VA. Mammographic density assessed on paired raw and processed digital images and on paired screen-film and digital images across three mammography systems. Breast Cancer Res. 2016 Dec.18(1):130. Pubmedid: 27993168. Pmcid: PMC5168805.
    • Wang H, Schabath MB, Liu Y, Berglund AE, Bloom GC, Kim J, Stringfield O, Eikman EA, Klippenstein DL, Heine JJ, Eschrich SA, Ye Z, Gillies RJ. Semiquantitative Computed Tomography Characteristics for Lung Adenocarcinoma and Their Association With Lung Cancer Survival. Clin Lung Cancer. 2015 Nov.16(6):e141-e163. Pubmedid: 26077095. Pmcid: PMC4609593.
    • Lu B, Smallwood AM, Sellers TA, Drukteinis JS, Heine JJ, Fowler EE. Calibrated breast density methods for full field digital mammography: a system for serial quality control and inter-system generalization. Med Phys. 2015 Feb.42(2):623-636. Pubmedid: 25652480. Pmcid: PMC4304962.
    • Kim S, Ramakrishnan R, Lavilla-Alonso S, Chinnaiyan P, Rao N, Fowler E, Heine J, Gabrilovich DI. Radiation-induced autophagy potentiates immunotherapy of cancer via up-regulation of mannose 6-phosphate receptor on tumor cells in mice. Cancer Immunol Immun. 2014 Oct.63(10):1009-1021. Pubmedid: 24943275. Pmcid: PMC4330093.
    • Fowler EE, Vachon CM, Scott CG, Sellers TA, Heine JJ. Automated Percentage of Breast Density Measurements for Full-field Digital Mammography Applications. Acad Radiol. 2014 Aug.21(8):958-970. Pubmedid: 25018067. Pmcid: PMC4166439.
    • Fowler EE, Lu B, Heine JJ. A comparison of calibration data from full field digital mammography units for breast density measurements. Biomed Eng Online. 2013 Nov.12:114. Pubmedid: 24207013. Pmcid: PMC3829208.
    • Fowler EE, Sellers TA, Lu B, Heine JJ. Breast Imaging Reporting and Data System (BI-RADS) breast composition descriptors: automated measurement development for full field digital mammography. Med Phys. 2013 Nov.40(11):113502. Pubmedid: 24320473. Pmcid: PMC3820635.
    • Behera M, Heine JJ, Sica GL, Fowler EE, Tran H, Fu RW, Gal AA, Hermann R, Mayfield W, Khuri FR, Owonikoko TK, Ramalingam SS. Survival analysis of patients with stage I non-small-cell lung cancer using clinical and DNA repair pathway expression variables. Clin Lung Cancer. 2013 Mar.14(2):128-138. Pubmedid: 22921042. Pmcid: PMC5787388.
    • Vachon CM, Fowler EE, Tiffenberg G, Scott CG, Pankratz VS, Sellers TA, Heine JJ. Comparison of percent density from raw and processed full-field digital mammography data. Breast Cancer Res. 2013 Jan.15(1):R1. Pubmedid: 23289950. Pmcid: PMC3672765.
    • Olson JE, Sellers TA, Scott CG, Schueler BA, Brandt KR, Serie DJ, Jensen MR, Wu FF, Morton MJ, Heine JJ, Couch FJ, Pankratz VS, Vachon CM. The influence of mammogram acquisition on the mammographic density and breast cancer association in the Mayo Mammography Health Study cohort. Breast Cancer Res. 2012 Nov.14(6):R147. Pubmedid: 23152984. Pmcid: PMC3701143.
    • Kumar NB, Vadaparampil ST, Mahajan N, Lilienfeld HS, Lee JH, Laronga C, Hakam A, Hein JJ, Egan KM, Arun B, Pal T. Metformin- A Promising Agent for Chemoprevention in BRCA1 Carriers. Hereditary Genet. 2012 Jun.1(2). Pubmedid: 26097796. Pmcid: PMC4474476.
    • Heine JJ, Scott CG, Sellers TA, Brandt KR, Serie DJ, Wu FF, Morton MJ, Schueler BA, Couch FJ, Olson JE, Pankratz VS, Vachon CM. A novel automated mammographic density measure and breast cancer risk. J Natl Cancer Inst. 2012 Jul.104(13):1028-1037. Pubmedid: 22761274. Pmcid: PMC3634551.
    • Mathur R, Schaffer JD, Land WH, Heine JJ, Hernandez JM, Yeatman T. Perturbation and candidate analysis to combat overfitting of gene expression microarray data. Int J Comput Biol Drug Des. 2012 Apr.4(4):307-315. Pubmedid: 22199032.
    • Behera M, Fowler EE, Owonikoko TK, Land WH, Mayfield W, Chen Z, Khuri FR, Ramalingam SS, Heine JJ. Statistical learning methods as a preprocessing step for survival analysis: evaluation of concept using lung cancer data. Biomed Eng Online. 2011 Nov.10:97. Pubmedid: 22067671. Pmcid: PMC3280940.
    • Heine JJ, Fowler EE, Flowers CI. Full field digital mammography and breast density: comparison of calibrated and noncalibrated measurements. Acad Radiol. 2011 Nov.18(11):1430-1436. Pubmedid: 21971260. Pmcid: PMC3190123.
    • Heine JJ, Cao K, Rollison DE, Tiffenberg G, Thomas JA. A quantitative description of the percentage of breast density measurement using full-field digital mammography. Acad Radiol. 2011 May.18(5):556-564. Pubmedid: 21474058. Pmcid: PMC3154681.
    • Heine JJ, Cao K, Rollison DE. Calibrated measures for breast density estimation. Acad Radiol. 2011 May.18(5):547-555. Pubmedid: 21371912. Pmcid: PMC3073034.
    • Heine JJ, Land WH, Egan KM. Statistical learning techniques applied to epidemiology: a simulated case-control comparison study with logistic regression. BMC Bioinformatics. 2011 Jan.12:37. Pubmedid: 21272346. Pmcid: PMC3045299.
    • Heine JJ, Cao K, Thomas JA. Effective radiation attenuation calibration for breast density: compression thickness influences and correction. Biomed Eng Online. 2010 Nov.9:73. Pubmedid: 21080916. Pmcid: PMC3000415.
    • Manduca A, Carston MJ, Heine JJ, Scott CG, Pankratz VS, Brandt KR, Sellers TA, Vachon CM, Cerhan JR. Texture features from mammographic images and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2009 Mar.18(3):837-845. Pubmedid: 19258482. Pmcid: PMC2674983.
    • Heine JJ, Cao K, Beam C. Cumulative sum quality control for calibrated breast density measurements. Med Phys. 2009 Dec.36(12):5380-5390. Pubmedid: 20095250. Pmcid: PMC2787061.
    • Heine JJ, Carston MJ, Scott CG, Brandt KR, Wu FF, Pankratz VS, Sellers TA, Vachon CM. An automated approach for estimation of breast density. Cancer Epidemiol Biomarkers Prev. 2008 Nov.17(11):3090-3097. Pubmedid: 18990749. Pmcid: PMC2705972.
    • Heine JJ, Thomas JA. Effective x-ray attenuation coefficient measurements from two full field digital mammography systems for data calibration applications. Biomed Eng Online. 2008 Mar.7:13. Pubmedid: 18373863. Pmcid: PMC2365951.
    • Land WH, Heine JJ, Raway T, Mizaku A, Kovalchuk N, Yang JY, Yang MQ. New statistical learning theory paradigms adapted to breast cancer diagnosis/classification using image and non-image clinical data. Int J Funct Inform Personal Med. 2008 Jan.1(2):111-139. Pubmedid: 26430470. Pmcid: PMC4587773.
    • Heine J, Behera M. Effective x-ray attenuation measurements with full field digital mammography. Med Phys. 2006 Nov.33(11):4350-4366. Pubmedid: 17153414.
    • Heine J, Behera M. Aspects of signal-dependent noise characterization. J Opt Soc Am A Opt Image Sci Vis. 2006 Apr.23(4):806-815. Pubmedid: 16604760.
    • Kumar N, Allen K, Riccardi D, Kazi A, Heine J. Isoflavones in breast cancer chemoprevention: where do we go from here?. Front Biosci (Landmark Ed). 2004 Sep.9:2927-2934. Pubmedid: 15353326.
    • Kallergi M, Heine J, Berman C, Hersh M, Romilly A, Clark R. Improved interpretation of digitized mammography with wavelet processing: a localization response operating characteristic study. Ajr Am J Roentgenol. 2004 Mar.182(3):697-703. Pubmedid: 14975972.
    • Heine J, Velthuizen R. Spectral analysis of full field digital mammography data. Med Phys. 2002 May.29(5):647-661. Pubmedid: 12033559.
    • Heine J, Malhotra P. Mammographic tissue, breast cancer risk, serial image analysis, and digital mammography. Part 1. Tissue and related risk factors. Acad Radiol. 2002 Mar.9(3):298-316. Pubmedid: 11887946.
    • Heine J, Malhotra P. Mammographic tissue, breast cancer risk, serial image analysis, and digital mammography. Part 2. Serial breast tissue change and related temporal influences. Acad Radiol. 2002 Mar.9(3):317-335. Pubmedid: 11887947.
    • Heine J, Velthuizen R. A statistical methodology for mammographic density detection. Med Phys. 2000 Dec.27(12):2644-2651. Pubmedid: 11190946.
    • Heine J, Deans S, Gaudadharan D, Clarke L. Multiresolution analysis of two-dimensional 1/f processes: approximation methods for random variable transformations. Optical Eng J. 1999 Sep.38(9):1505-1516.
    • Heine, Deans, Velthuizen, Clarke. On the statistical nature of mammograms. Med Phys. 1999 Nov.26(11):2254-2265. Pubmedid: 10587206.
    • Heine J, Deans S, Clarke L. Multiresolution probability analysis of random fields. J Opt Soc Am. 1999 Jan.16(1):6-16. Pubmedid: noPMID.
    • Heine J, Deans S. Multiresolution probability analysis of gray-scaled images. J Opt Soc Am. 1998.A15:1048-1058. Pubmedid: noPMID.
    • Heine J, Deans S, Cullers D, Stauduhar R, Clarke L. Multiresolution statistical analysis of high-resolution digital mammograms. Ieee T Med Imaging. 1997 Oct.16(5):503-515. Pubmedid: 9368106.
    • Kallergi M, Berman C, Heine J, Hersh M, Hooper L, Kim J, Miller M, Galbo C, Thomas J, Clark R. Effect of default display and presentation protocol on softcopy mammography. In: Digital Mammography IWDM 2002. New York, NY: Springer-Verlag; 2003;202.
  • Grants

    • Title: Stromal Contributions to Breast Carcinogenesis
      Sponsor: Nat Institutes of Health
      PI: Heine, J.
    • Title: Quantitative Imaging Clinical Validation Center at Moffitt Cancer Center
      Sponsor: Nat Institutes of Health
      PI (Contact): Heine, J., PI (MPI): Schabath, M.

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