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Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer

  • David GroheuxEmail author
  • Sylvie Giacchetti
  • Jean-Luc Moretti
  • Raphael Porcher
  • Marc Espié
  • Jacqueline Lehmann-Che
  • Anne de Roquancourt
  • Anne-Sophie Hamy
  • Caroline Cuvier
  • Laetitia Vercellino
  • Elif Hindié
Original Article

Abstract

Purpose

The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on 18F-fluorodeoxyglucose (FDG) uptake. Only women with tumours larger than 20 mm (T2–T4) were included in order to minimize bias of partial volume effect.

Methods

In this prospective study, 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy. Maximum standardized uptake values (SUVmax) were compared to tumour characteristics as assessed on core biopsy.

Results

There was no influence of T and N stage on SUV. Invasive ductal carcinoma showed higher SUV than lobular carcinoma. However, the highest uptake was found for metaplastic tumours, representing 5% of patients in this series. Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake: the median of SUVmax was 9.7 for grade 3 tumours vs 4.8 for the lower grades (p < 0.0001); negativity for oestrogen receptors (ER) was associated with higher SUV (ER+ SUV = 5.5; ER− SUV = 7.6; p = 0.003); triple-negative tumours (oestrogen and progesterone receptor negative, no overexpression of c-erbB-2) had an SUV of 9.2 vs 5.8 for all others (p = 0005); p53 mutated tumours also had significantly higher SUV (7.8 vs 5.0; p < 0.0001). Overexpression of c-erbB-2 had no effect on the SUV value.

Conclusion

Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans. Also, findings that FDG uptake is highest in those patients with poor prognostic features (high grade, hormone receptor negativity, triple negativity, metaplastic tumours) is helpful to determine who are the best candidates for baseline staging.

Keywords

SUV 18F-FDG uptake PET/CT Breast cancer Molecular biomarkers 

Notes

Acknowledgements

We are grateful to “Fondation Clarence” for their help in editing this manuscript.

Financial support

None.

Conflicts of interest

None.

References

  1. 1.
    Groheux D, Giacchetti S, Rubello D, Al-Nahhas A, Moretti JL, Espié M, et al. The evolving role of PET/CT in breast cancer. Nucl Med Commun 2010;31:271–3.CrossRefPubMedGoogle Scholar
  2. 2.
    Berriolo-Riedinger A, Touzery C, Riedinger JM, Toubeau M, Coudert B, Arnould L, et al. [18F]FDG-PET predicts complete pathological response of breast cancer to neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging 2007;34:1915–24.CrossRefPubMedGoogle Scholar
  3. 3.
    Dehdashti F, Mortimer JE, Siegel BA, Griffeth LK, Bonasera TJ, Fusselman MJ, et al. Positron tomographic assessment of estrogen receptors in breast cancer: comparison with FDG-PET and in vitro receptor assays. J Nucl Med 1995;36:1766–74.PubMedGoogle Scholar
  4. 4.
    Crippa F, Seregni E, Agresti R, Chiesa C, Pascali C, Bogni A, et al. Association between [18F]fluorodeoxyglucose uptake and postoperative histopathology, hormone receptor status, thymidine labelling index and p53 in primary breast cancer: a preliminary observation. Eur J Nucl Med 1998;25:1429–34.CrossRefPubMedGoogle Scholar
  5. 5.
    Avril N, Menzel M, Dose J, Schelling M, Weber W, Jänicke F, et al. Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis. J Nucl Med 2001;42:9–16.PubMedGoogle Scholar
  6. 6.
    Buck A, Schirrmeister H, Kühn T, Shen C, Kalker T, Kotzerke J, et al. FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. Eur J Nucl Med Mol Imaging 2002;29:1317–23.CrossRefPubMedGoogle Scholar
  7. 7.
    Bos R, van Der Hoeven JJ, van Der Wall E, van Der Groep P, van Diest PJ, Comans EF, et al. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 2002;20:379–87.CrossRefPubMedGoogle Scholar
  8. 8.
    Kumar R, Chauhan A, Zhuang H, Chandra P, Schnall M, Alavi A. Clinicopathologic factors associated with false negative FDG-PET in primary breast cancer. Breast Cancer Res Treat 2006;98:267–74.CrossRefPubMedGoogle Scholar
  9. 9.
    Groheux D, Moretti JL, Baillet G, Espie M, Giacchetti S, Hindie E, et al. Effect of (18)F-FDG PET/CT imaging in patients with clinical stage II and III breast cancer. Int J Radiat Oncol Biol Phys 2008;71:695–704.CrossRefPubMedGoogle Scholar
  10. 10.
    Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 2002;20:3628–36.CrossRefPubMedGoogle Scholar
  11. 11.
    Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991;19:403–10. Comment in Histopathology 2002;41:151–2.CrossRefPubMedGoogle Scholar
  12. 12.
    Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999;17:1474–81.PubMedGoogle Scholar
  13. 13.
    Zafrani B, Aubriot MH, Mouret E, De Crémoux P, De Rycke Y, Nicolas A, et al. High sensitivity and specificity of immunohistochemistry for the detection of hormone receptors in breast carcinoma: comparison with biochemical determination in a prospective study of 793 cases. Histopathology 2000;37:536–45.CrossRefPubMedGoogle Scholar
  14. 14.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 2007;131:18–43.PubMedGoogle Scholar
  15. 15.
    Flaman JM, Frebourg T, Moreau V, Charbonnier F, Martin C, Chappuis P, et al. A simple p53 functional assay for screening cell lines, blood, and tumors. Proc Natl Acad Sci U S A 1995;92:3963–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Avril N, Rosé CA, Schelling M, Dose J, Kuhn W, Bense S, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol 2000;18:3495–502.PubMedGoogle Scholar
  17. 17.
    Gil-Rendo A, Martínez-Regueira F, Zornoza G, García-Velloso MJ, Beorlegui C, Rodriguez-Spiteri N. Association between [18F]fluorodeoxyglucose uptake and prognostic parameters in breast cancer. Br J Surg 2009;96:166–70.CrossRefPubMedGoogle Scholar
  18. 18.
    Buck AK, Schirrmeister H, Mattfeldt T, Reske SN. Biological characterisation of breast cancer by means of PET. Eur J Nucl Med Mol Imaging 2004;31:S80–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Jung SY, Kim HY, Nam BH, Min SY, Lee SJ, Park C, et al. Worse prognosis of metaplastic breast cancer patients than other patients with triple-negative breast cancer. Breast Cancer Res Treat 2010;120:627–37.CrossRefPubMedGoogle Scholar
  20. 20.
    Ikenaga N, Otomo N, Toyofuku A, Ueda Y, Toyoda K, Hayashi T, et al. Standardized uptake values for breast carcinomas assessed by fluorodeoxyglucose-positron emission tomography correlate with prognostic factors. Am Surg 2007;73:1151–7.PubMedGoogle Scholar
  21. 21.
    Shimoda W, Hayashi M, Murakami K, Oyama T, Sunagawa M. The relationship between FDG uptake in PET scans and biological behavior in breast cancer. Breast Cancer 2007;14:260–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Mavi A, Cermik TF, Urhan M, Puskulcu H, Basu S, Yu JQ, et al. The effects of estrogen, progesterone, and C-erbB-2 receptor states on 18F-FDG uptake of primary breast cancer lesions. J Nucl Med 2007;48:1266–72.CrossRefPubMedGoogle Scholar
  23. 23.
    Osborne JR, Port E, Gonen M, Doane A, Yeung H, Gerald W, et al. 18F-FDG PET of locally invasive breast cancer and association of estrogen receptor status with standardized uptake value: microarray and immunohistochemical analysis. J Nucl Med 2010;51:543–50.CrossRefPubMedGoogle Scholar
  24. 24.
    Laudański P, Koda M, Kozłowski L, Swiatecka J, Wojtukiewicz M, Sulkowski S, et al. Expression of glucose transporter GLUT-1 and estrogen receptors ER-alpha and ER-beta in human breast cancer. Neoplasma 2004;51:164–8.PubMedGoogle Scholar
  25. 25.
    Paik S, Kim C, Wolmark N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med 2008;358:1409–11.CrossRefPubMedGoogle Scholar
  26. 26.
    Ueda S, Tsuda H, Asakawa H, Shigekawa T, Fukatsu K, Kondo N, et al. Clinicopathological and prognostic relevance of uptake level using 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in primary breast cancer. Jpn J Clin Oncol 2008;38:250–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Bertheau P, Turpin E, Rickman DS, Espié M, de Reyniès A, Feugeas JP, et al. Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen. PLoS Med 2007;4:e90.CrossRefPubMedGoogle Scholar
  28. 28.
    Norberg T, Lennerstrand J, Inganäs M, Bergh J. Comparison between p53 protein measurements using the luminometric immunoassay and immunohistochemistry with detection of p53 gene mutations using cDNA sequencing in human breast tumors. Int J Cancer 1998;79:376–83.CrossRefPubMedGoogle Scholar
  29. 29.
    Manié E, Vincent-Salomon A, Lehmann-Che J, Pierron G, Turpin E, Warcoin M, et al. High frequency of TP53 mutation in BRCA1 and sporadic basal-like carcinomas but not in BRCA1 luminal breast tumors. Cancer Res 2009;69:663–71.CrossRefPubMedGoogle Scholar
  30. 30.
    Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E. The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res 2004;64:2627–33.CrossRefPubMedGoogle Scholar
  31. 31.
    Vousden KH, Ryan KM. p53 and metabolism. Nat Rev Cancer 2009;9:691–700.CrossRefPubMedGoogle Scholar
  32. 32.
    Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006;126:107–20.CrossRefPubMedGoogle Scholar
  33. 33.
    Smith TA, Sharma RI, Thompson AM, Paulin FE. Tumour 18F-FDG incorporation is enhanced by attenuation of P53 function in breast cancer cells in vitro. J Nucl Med 2006;47:1525–30.PubMedGoogle Scholar
  34. 34.
    Dawson SJ, Provenzano E, Caldas C. Triple negative breast cancers: clinical and prognostic implications. Eur J Cancer 2009;45 Suppl 1:27–40.CrossRefPubMedGoogle Scholar
  35. 35.
    Basu S, Chen W, Tchou J, Mavi A, Cermik T, Czerniecki B, et al. Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization. Cancer 2008;112:995–1000.CrossRefPubMedGoogle Scholar
  36. 36.
    Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98:10869–74.CrossRefPubMedGoogle Scholar
  37. 37.
    Troester MA, Herschkowitz JI, Oh DS, He X, Hoadley KA, Barbier CS, et al. Gene expression patterns associated with p53 status in breast cancer. BMC Cancer 2006;6:276.CrossRefPubMedGoogle Scholar
  38. 38.
    Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic markers in triple-negative breast cancer. Cancer 2007;109:25–32.CrossRefPubMedGoogle Scholar
  39. 39.
    Edge SB, Byrd DR, Conyton CC, Fritz AG, Greene FL, Trotti A. AJCC Cancer Staging Manual 7th Edition. Springer 2010.Google Scholar
  40. 40.
    van der Hoeven JJ, Krak NC, Hoekstra OS, Comans EF, Boom RP, van Geldere D, et al. 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer. J Clin Oncol 2004;22(7):1253–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Alberini JL, Lerebours F, Wartski M, Fourme E, Le Stanc E, Gontier E, et al. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging in the staging and prognosis of inflammatory breast cancer. Cancer 2009;115:5038–47.CrossRefPubMedGoogle Scholar
  42. 42.
    Fuster D, Duch J, Paredes P, Velasco M, Muñoz M, Santamaría G, et al. Preoperative staging of large primary breast cancer with [18F]fluorodeoxyglucose positron emission tomography/computed tomography compared with conventional imaging procedures. J Clin Oncol 2008;26:4746–51.CrossRefPubMedGoogle Scholar
  43. 43.
    Oshida M, Uno K, Suzuki M, Nagashima T, Hashimoto H, Yagata H, et al. Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose. Cancer 1998;82:2227–34.CrossRefPubMedGoogle Scholar
  44. 44.
    Inoue T, Yutani K, Taguchi T, Tamaki Y, Shiba E, Noguchi S. Preoperative evaluation of prognosis in breast cancer patients by [(18)F]2-deoxy-2-fluoro-D-glucose-positron emission tomography. J Cancer Res Clin Oncol 2004;130:273–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Uematsu T, Kasami M, Yuen S. Comparison of FDG PET and MRI for evaluating the tumor extent of breast cancer and the impact of FDG PET on the systemic staging and prognosis of patients who are candidates for breast-conserving therapy. Breast Cancer 2009;16:97–104.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • David Groheux
    • 1
    • 2
    Email author
  • Sylvie Giacchetti
    • 3
  • Jean-Luc Moretti
    • 1
    • 2
  • Raphael Porcher
    • 4
  • Marc Espié
    • 3
  • Jacqueline Lehmann-Che
    • 5
  • Anne de Roquancourt
    • 6
  • Anne-Sophie Hamy
    • 3
  • Caroline Cuvier
    • 3
  • Laetitia Vercellino
    • 1
  • Elif Hindié
    • 1
    • 2
  1. 1.Department of Nuclear Medicine, Saint-Louis Hospital,Assistance publique Hôpitaux de ParisParis Cedex 10France
  2. 2.IUH, Doctoral School, University of Paris VIIParisFrance
  3. 3.Department of Medical OncologyBreast Diseases Unit, Saint-Louis HospitalParisFrance
  4. 4.Department of Biostatistics and Medical InformationSaint-Louis HospitalParisFrance
  5. 5.Department of BiochemistrySaint-Louis HospitalParisFrance
  6. 6.Department of PathologySaint-Louis HospitalParisFrance

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