Molecular imaging approaches in the diagnosis of breast cancer: A systematic review and meta-analysis

Document Type: Systematic Review/Meta-analysis

Authors

1 Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 International Campus, Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Physics, College of Natural Sciences, Aksum University, Aksum, Ethiopia

4 Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran

5 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

6 PET/CT and Cyclotron Center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

7 Department of Public Health, College of Medical and Health Sciences, Ambo University, Ambo, Ethiopia

8 Department of Physics, Faculty of Natural Sciences, Debre Tabor University, Debre Tabor, Ethiopia

9 Department of Biology, College of Natural Sciences, Jimma University, Jimma, Ethiopia

10 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

11 Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Introduction:The accuracy of positron emission tomography with computed tomography (PET/CT), positron emission mammography (PEM), and breast specific-gamma imaging (BSGI) in diagnosing breast cancer has never been systematically assessed, the present systematic review was aimed to address this issue. 
Methods:PubMed, Scopus and EMBASE were searched for studies dealt with the detection of breast cancer by PET/CT, PEM or BSGI. Histopathologic examination and/or at least six months imaging follow-up were used as a golden reference. To calculate diagnostic test parameters: sensitivity, specificity, summary receiver operating characteristic curves (SROC) and to test for heterogeneity, true positive (TP), true negative (TN), false positive (FP) and false negative (FN) were extracted.
Results: Thirty one studies were included in the analysis. On per-patient basis, the pooled sensitivities after corrected for threshold effect for 18F-FDG PET/CT, PEM, and 99mTc-MIBI BSGI were 0.89 (95% CI: 0.78- 0.95), 0.73 (95% CI: 0.41 - 0.92), and 0.80 (95% CI: 0.72 - 0.86) respectively. The pooled specificities for detection of breast cancer using FDG PET/CT, PEM, and 99mTc-MIBI BSGI were 0.93 (95 % CI, 0.86 - 0.96), 0.91 (95 % CI, 0.77- 96), and 0.78 (95 % CI, 0.64 - 0.88), respectively. AUC of FDG PET/CT, PEM, and BSGI were 0.9549, 0.8852 and 0.8573, respectively.
Conclusion: This meta-analysis indicated that PET/CT showed better diagnostic accuracy than PEM, and BSGI on per-patient basis. On per-lesion analysis, PEM with the highest AUC, DOR and Q* was better than PET/CT, and BSGI for detecting breast cancer.

Keywords

Main Subjects


  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424.
  2. Habib S, Maseeh-uz-Zaman, Hameed A, Niaz K, Hashmi H, Kamal S. Diagnostic accuracy of Tc-99m-MIBI for breast carcinoma in correlation with mammography and sonography. J Coll Physicians Surg Pak. 2009 Oct;19(10):622-6.
  3. Khatcheressian JL, Wolff AC, Smith TJ, Grunfeld E, Muss HB, Vogel VG, Halberg F, Somerfield MR, Davidson NE. American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol. 2006 Nov 1;24(31):5091-7.
  4. Rissanen TJ, Mäkäräinen HP, Mattila SI, Lindholm EL, Heikkinen MI, Kiviniemi HO. Breast cancer recurrence after mastectomy: diagnosis with mammography and US. Radiology. 1993 Aug;188(2):463-7.
  5. Rosenberg RD, Hunt WC, Williamson MR, Gilliland FD, Wiest PW, Kelsey CA, Key CR, Linver MN. Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico. Radiology. 1998 Nov;209(2):511-8.
  6. Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G, Chiarelli A, Minkin S, Yaffe MJ. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007 Jan 18;356(3):227-36.
  7. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009 Jul 21;6(7):e1000100.
  8. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003 Nov 10;3:25.
  9. Fleiss JL. Statistical methods for rates and proportions. 2nd ed. Wiley-Interscience;1981.
  10. Sadeghi R.Treglia G. Systematic reviews and meta-analyses of diagnostic studies: a practical guideline. Clin Transl Imaging 2017;5(2):83-87.
  11. Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 1993 Jul 30;12(14):1293-316.
  12. Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005 Oct;58(10):982-90.
  13. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002 Jun 15;21(11):1539-58.
  14. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997 Sep 13;315(7109):629-34.
  15. Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol. 2003 Nov;56(11):1129-35.
  16. Aukema TS, Rutgers EJ, Vogel WV, Teertstra HJ, Oldenburg HS, Vrancken Peeters MT, Wesseling J, Russell NS, Valdés Olmos RA. The role of FDG PET/CT in patients with locoregional breast cancer recurrence: a comparison to conventional imaging techniques. Eur J Surg Oncol. 2010 Apr;36(4):387-92.
  17. Berg WA, Madsen KS, Schilling K, Tartar M, Pisano ED, Larsen LH, Narayanan D, Ozonoff A, Miller JP, Kalinyak JE. Breast cancer: comparative effectiveness of positron emission mammography and MR imaging in presurgical planning for the ipsilateral breast. Radiology. 2011 Jan;258(1):59-72.
  18. Brem RF, Ruda RC, Yang JL, Coffey CM, Rapelyea JA. Breast-Specific γ-Imaging for the Detection of Mammographically Occult Breast Cancer in Women at Increased Risk. J Nucl Med. 2016 May;57(5):678-84.
  19. Champion L, Brain E, Giraudet AL, Le Stanc E, Wartski M, Edeline V, Madar O, Bellet D, Pecking A, Alberini JL. Breast cancer recurrence diagnosis suspected on tumor marker rising: value of whole-body 18FDG-PET/CT imaging and impact on patient management. Cancer. 2011 Apr 15;117(8):1621-9.
  20. Cho MJ, Yang JH, Yu YB, Park KS Chung HW, So Y, Choi N, Kim MY. Validity of breast-specific gamma imaging for Breast Imaging Reporting and Data System 4 lesions on mammography and/or ultrasound. Ann Surg Treat Res. 2016 Apr;90(4):194-200.
  21. Dai D, Song X, Wang M, Li L, Ma W, Xu W, Ma Y, Liu J, Zhang J, Liu P, Gu X, Su Y. Comparison of Diagnostic Performance of Three-Dimensional Positron Emission Mammography versus Whole Body Positron Emission Tomography in Breast Cancer. Contrast Media Mol Imaging. 2017 Jul 3;2017:5438395.
  22. Jung NY, Yoo IR, Kang BJ, Kim SH, Chae BJ, Seo YY. Clinical significance of FDG-PET/CT at the postoperative surveillance in the breast cancer patients. Breast Cancer. 2016 Jan;23(1):141-148.
  23. Kalinyak JE, Berg WA, Schilling K, Madsen KS, Narayanan D, Tartar M. Breast cancer detection using high-resolution breast PET compared to whole-body PET or PET/CT. Eur J Nucl Med Mol Imaging. 2014 Feb;41(2):260-75.
  24. Kim BS. Usefulness of breast-specific gamma imaging as an adjunct modality in breast cancer patients with dense breast: a comparative study with MRI. Ann Nucl Med. 2012 Feb;26(2):131-7.
  25. Kim S, Plemmons J, Hoang K, Chaudhuri D, Kelley A, Cunningham T, Hoefer R. Breast-specific gamma imaging versus mri: comparing the diagnostic performance in assessing treatment response after neoadjuvant chemotherapy in patients with breast cancer. AJR Am J Roentgenol. 2019 Mar;212(3):696-705.
  26. Kim YH, Lee JA, Baek JM, Sung GY, Lee DS, Won JM. The clinical significance of standardized uptake value in breast cancer measured using 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Nucl Med Commun. 2015 Aug;36(8):790-4.
  27. Koolen BB, van der Leij F, Vogel WV, Rutgers EJ, Vrancken Peeters MJ, Elkhuizen PH, Valdés Olmos RA. Accuracy of 18F-FDG PET/CT for primary tumor visualization and staging in T1 breast cancer. Acta Oncol. 2014 Jan;53(1):50-7.
  28. Koolen BB, Vrancken Peeters MJ, Aukema TS, Vogel WV, Oldenburg HS, van der Hage JA, Hoefnagel CA, Stokkel MP, Loo CE, Rodenhuis S, Rutgers EJ, Valdés Olmos RA. 18F-FDG PET/CT as a staging procedure in primary stage II and III breast cancer: comparison with conventional imaging techniques. Breast Cancer Res Treat. 2012 Jan;131(1):117-26.
  29. Lee A, Chang J, Lim W, Kim BS, Lee JE, Cha ES, Moon BI. Effectiveness of breast-specific gamma imaging (BSGI) for breast cancer in Korea: a comparative study. Breast J. 2012 Sep;18(5):453-8.
  30. Lee HS, Ko BS, Ahn SH, Son BH, Lee JW, Kim HJ, Yu JH, Kim SB, Jung KH, Ahn JH, Cha JH, Kim HH, Lee HJ, Song IH, Gong G, Park SH, Lee JJ, Moon DH. Diagnostic performance of breast-specific gamma imaging in the assessment of residual tumor after neoadjuvant chemotherapy in breast cancer patients Breast Cancer Res Treat. 2014 May;145(1):91-100.
  31. Magometschnigg HF, Baltzer PA, Fueger B, Helbich TH, Karanikas G, Dubsky P, Rudas M, Weber M, Pinker K. Diagnostic accuracy of (18)F-FDG PET/CT compared with that of contrast-enhanced MRI of the breast at 3 T. Eur J Nucl Med Mol Imaging. 2015 Oct;42(11):1656-1665.
  32. Meissnitzer T, Seymer A, Keinrath P, Holzmannhofer J Pirich C, Hergan K, Meissnitzer MW. Added value of semi-quantitative breast-specific gamma imaging in the work-up of suspicious breast lesions compared to mammography, ultrasound and 3-T MRI. Br J Radiol. 2015 Jul;88(1051):20150147.
  33. Müller FHH, Michael H, Müller AG, Farahati J. PEM tests will have a high accuracy detecting breast cancer, if an individualized dosage of F-18-FDG is used. Cancer Res. 2015; DOI: 10.1158/1538-7445.
  34. Murakami R, Kumita S, Yoshida T, Ishihara K, Kiriyama T, Hakozaki K, Yanagihara K, Iida S, Tsuchiya S. FDG-PET/CT in the diagnosis of recurrent breast cancer. Acta Radiol. 2012 Feb 1;53(1):12-6.
  35. Nakajo M, Kajiya Y, Kaneko T, Kaneko Y, Takasaki T, Tani A, Ueno M, Koriyama C, Nakajo M. FDG PET/CT and diffusion-weighted imaging for breast cancer: prognostic value of maximum standardized uptake values and apparent diffusion coefficient values of the primary lesion. Eur J Nucl Med Mol Imaging. 2010 Nov;37(11):2011-20.
  36. Niikura N, Costelloe CM, Madewell JE, Hayashi N, Yu TK, Liu J, Palla SL, Tokuda Y, Theriault RL, Hortobagyi GN, Ueno NT. FDG-PET/CT compared with conventional imaging in the detection of distant metastases of primary breast cancer. Oncologist. 2011;16(8):1111-9.
  37. Park JS, Lee AY, Jung KP, Choi SJ, Lee SM, Kyun Bae S. Diagnostic Performance of Breast-Specific Gamma Imaging (BSGI) for Breast Cancer: Usefulness of Dual-Phase Imaging with (99m)Tc-sestamibi. Nucl Med Mol Imaging. 2013 Mar;47(1):18-26.
  38. Park KS, Chung HW, Yoo YB, Yang JH, Choi N, So Y. Complementary role of semiquantitative analysis of breast-specific gamma imaging in the diagnosis of breast cancer. AJR Am J Roentgenol. 2014 Mar;202(3):690-5.
  39. Schilling K, Narayanan D, Kalinyak JE, The J, Velasquez MV, Kahn S, Saady M, Mahal R, Chrystal L. Positron emission mammography in breast cancer presurgical planning: comparisons with magnetic resonance imaging. Eur J Nucl Med Mol Imaging. 2011 Jan;38(1):23-36.
  40. Vassiou K, Kanavou T, Vlychou M, Poultsidi A, Athanasiou E, Arvanitis DL, Fezoulidis IV. Characterization of breast lesions with CE-MR multimodal morphological and kinetic analysis: comparison with conventional mammography and high-resolution ultrasound. Eur J Radiol. 2009 Apr;70(1):69-76.
  41. Yamamoto Y, Ozawa Y, Kubouchi K, Nakamura S, Nakajima Y, Inoue T. Comparative analysis of imaging sensitivity of positron emission mammography and whole-body PET in relation to tumor size. Clin Nucl Med. 2015 Jan;40(1):21-5.
  42. Yano F, Itoh M, Hirakawa H, Yamamoto S, Yoshikawa A, Hatazawa J. Diagnostic Accuracy of Positron Emission Mammography with 18F-fluorodeoxyglucose in Breast Cancer Tumor of Less than 20 mm in Size. Asia Ocean J Nucl Med Biol. 2019 Winter;7(1):13-21.
  43. Yu X, Hu G, Zhang Z, Qiu F, Shao X, Wang X, Zhan H, Chen Y, Deng Y, Huang J. Retrospective and comparative analysis of (99m)Tc-Sestamibi breast specific gamma imaging versus mammography, ultrasound, and magnetic resonance imaging for the detection of breast cancer in Chinese women. BMC Cancer. 2016 Jul 11;16:450.
  44. Berg WA, Madsen KS, Schilling K, Tartar M, Pisano ED, Larsen LH, Narayanan D, Kalinyak JE. Comparative effectiveness of positron emission mammography and MRI in the contralateral breast of women with newly diagnosed breast cancer. AJR Am J Roentgenol. 2012 Jan;198(1):219-32.
  45. Bitencourt AG, Lima EN, Macedo BR, Conrado JL, Marques EF, Chojniak R. Can positron emission mammography help to identify clinically significant breast cancer in women with suspicious calcifications on mammography? Eur Radiol. 2017 May;27(5):1893-1900.
  46. Müller FHH, Hentschel M, Müller AG, Farahati J. High accuracy of Positron Emission Mammography (PEM) in diagnosis of breast cancer. Eur J Nucl Med Mol Imaging. 2014;(41):S472.
  47. Kalles V, Zografos GC, Provatopoulou X, Koulocheri D, Gounaris A. The current status of positron emission mammography in breast cancer diagnosis. Breast Cancer. 2013 Apr;20(2):123-30.
  48. Rong J, Wang S, Ding Q, Yun M, Zheng Z, Ye S. Comparison of 18 FDG PET-CT and bone scintigraphy for detection of bone metastases in breast cancer patients. A meta-analysis. Surg Oncol. 2013 Jun;22(2):86-91.
  49. Tatsumi M, Cohade C, Mourtzikos KA, Fishman EK, Wahl RL. Wahl, Initial experience with FDG-PET/CT in the evaluation of breast cancer. Eur J Nucl Med Mol Imaging. 2006 Mar;33(3):254-62.
  50. Xiao Y, Wang L, Jiang X, She W, He L, Hu G. Diagnostic efficacy of 18F-FDG-PET or PET/CT in breast cancer with suspected recurrence: a systematic review and meta-analysis. Nucl Med Commun. 2016 Nov;37(11):1180-8.
  51. Eubank WB, Mankoff D, Bhattacharya M, Gralow J, Linden H, Ellis G, Lindsley S, Austin-Seymour M, Livingston R. Impact of FDG PET on defining the extent of disease and on the treatment of patients with recurrent or metastatic breast cancer. AJR Am J Roentgenol. 2004 Aug;183(2):479-86.
  52. Radan L, Ben-Haim S, Bar-Shalom R, Guralnik L, Israel O. The role of FDG‐PET/CT in suspected recurrence of breast cancer. Cancer. 2006 Dec 1;107(11):2545-51.
  53. Caldarella C, Treglia G, Giordano A. Diagnostic performance of dedicated positron emission mammography using fluorine-18-fluorodeoxyglucose in women with suspicious breast lesions: a meta-analysis. Clin Breast Cancer. 2014 Aug;14(4):241-8.
  54. Levine EA, Freimanis RI, Perrier ND, Morton K, Lesko NM, Bergman S, Geisinger KR, Williams RC, Sharpe C, Zavarzin V, Weinberg IN, Stepanov PY, Beylin D, Lauckner K, Doss M, Lovelace J, Adler LP. Positron emission mammography: initial clinical results. Annals of Ann Surg Oncol. 2003 Jan-Feb;10(1):86-91.
  55. Murthy K, Aznar M, Thompson CJ, Loutfi A, Lisbona R, Gagnon JH. Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG. J Nucl Med. 2000 Nov;41(11):1851-8.
  56. Tafra L, Cheng Z, Uddo J, Lobrano MB, Stein W, Berg WA, Levine E, Weinberg IN, Narayanan D, Ross E, Beylin D, Yarnall S, Keen R, Sawyer K, Van Geffen J, Freimanis RL, Staab E, Adler LP, Lovelace J, Shen P, Stewart J, Dolinsky S. Pilot clinical trial of 18F-fluorodeoxyglucose positron-emission mammography in the surgical management of breast cancer. Am J Surg. 2005 Oct;190(4):628-32.
  57. Eo JS, Chun IK, Paeng JC, Kang KW, Lee SM, Han W, Noh DY, Chung JK, Lee DS. Imaging sensitivity of dedicated positron emission mammography in relation to tumor size. Breast. 2012 Feb;21(1):66-71.
  58. Berg WA, Weinberg IN, Narayanan D, Lobrano ME, Ross E, Amodei L, Tafra L, Adler LP, Uddo J, Stein W 3rd, Levine EA; Positron Emission Mammography Working Group. High-resolution fluorodeoxyglucose positron emission tomography with compression ("positron emission mammography") is highly accurate in depicting primary breast cancer. Breast J. 2006 Jul-Aug;12(4):309-23.
  59. Brem RF, Ioffe M, Rapelyea JA, Yost KG, Weigert JM, Bertrand ML, Stern LH. Invasive lobular carcinoma: detection with mammography, sonography, MRI, and breast-specific gamma imaging. AJR Am J Roentgenol. 2009 Feb;192(2):379-83.
  60. Hruska CB, O'Connor MK. Quantification of lesion size, depth, and uptake using a dual-head molecular breast imaging system. Med Phys. 2008 Apr;35(4):1365-76.
  61. Zhang A, Li P, Liu Q, Song S. Breast-specific gamma camera imaging with 99mTc-MIBI has better diagnostic performance than magnetic resonance imaging in breast cancer patients: A meta-analysis. Hell J Nucl Med. 2017 Jan-Apr;20(1):26-35.
  62. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989 Jan 1;63(1):181-7.
  63. Sun Y, Wei W, Yang HW, Liu JL. Clinical usefulness of breast-specific gamma imaging as an adjunct modality to mammography for diagnosis of breast cancer: a systemic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2013 Feb;40(3):450-63.
  64. Berg WA, Gutierrez L, NessAiver MS, Carter WB, Bhargavan M, Lewis RS, Ioffe OB. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology. 2004 Dec;233(3):830-49.
  65. Krecke KN, Gisvold JJ. Invasive lobular carcinoma of the breast: mammographic findings and extent of disease at diagnosis in 184 patients. AJR Am J Roentgenol. 1993 Nov;161(5):957-60.
  66. Uchiyama N, Miyakawa K, Moriyama N, Kumazaki T. Radiographic features of invasive lobular carcinoma of the breast. Radiat Med. 2001 Jan-Feb;19(1):19-25.
  67. Spanu A, Farris A, Chessa F, Sanna D, Pittalis M, Manca A, Madeddu G. Planar scintimammography and SPECT in neoadjuvant chemo or hormonotherapy response evaluation in locally advanced primary breast cancer. Int J Oncol. 2008 Jun;32(6):1275-83.
  68. Kessler R, Sutcliffe JB, Bell L, Bradley YC, Anderson S, Banks KP. Negative predictive value of breast-specific gamma imaging in low suspicion breast lesions: a potential means for reducing benign biopsies. Breast J. 2011 May-Jun;17(3):319-21.
  69. Rhodes DJ, Hruska CB, Phillips SW, Whaley DH, O'Connor MK. Dedicated dual-head gamma imaging for breast cancer screening in women with mammographically dense breasts. Radiology. 2011 Jan;258(1):106-18.
  70. Hruska CB, Weinmann AL, O'Connor MK. Proof of concept for low-dose molecular breast imaging with a dual-head CZT gamma camera. Part I. Evaluation in phantoms. Med Phys. 2012 Jun;39(6):3466-75.
  71. Hruska CB, Weinmann AL, Tello Skjerseth CM, Wagenaar EM, Conners AL, Tortorelli CL, Maxwell RW, Rhodes DJ, O'Connor MK. Proof of concept for low-dose molecular breast imaging with a dual-head CZT gamma camera. Part II. Evaluation in patients. Med Phys. 2012 Jun;39(6):3476-83.