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Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

  • B. B. Koolen
  • M. J. T. F. D. Vrancken Peeters
  • J. Wesseling
  • E. H. Lips
  • W. V. Vogel
  • T. S. Aukema
  • E. van Werkhoven
  • K. G. A. Gilhuijs
  • S. Rodenhuis
  • E. J. Th. Rutgers
  • R. A. Valdés Olmos
Original Article

Abstract

Purpose

The aim of this study was to evaluate the association of primary tumour 18F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake.

Methods

PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUVmax). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses.

Results

In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUVmax was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUVmax.

Conclusion

Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT.

Keywords

Breast cancer PET/CT Subtype Prognosis Characteristics Response monitoring 

Notes

Acknowledgements

This study was performed within the framework of CTMM, the Center for Translational and Molecular Medicine (www.ctmm.nl), project Breast CARE (grant 03O-104).

Conflicts of interest

None.

References

  1. 1.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277–300.PubMedCrossRefGoogle Scholar
  2. 2.
    Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, et al. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 2008;26:2373–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Simpson JF, Gray R, Dressler LG, Cobau CD, Falkson CI, Gilchrist KW, et al. Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189. J Clin Oncol 2000;18:2059–69.PubMedGoogle Scholar
  4. 4.
    van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002;415:530–6.CrossRefGoogle Scholar
  5. 5.
    Miles KA, Williams RE. Warburg revisited: imaging tumour blood flow and metabolism. Cancer Imaging 2008;8:81–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Paesmans M, Berghmans T, Dusart M, Garcia C, Hossein-Foucher C, Lafitte JJ, et al. Primary tumor standardized uptake value measured on fluorodeoxyglucose positron emission tomography is of prognostic value for survival in non-small cell lung cancer: update of a systematic review and meta-analysis by the European Lung Cancer Working Party for the International Association for the Study of Lung Cancer Staging Project. J Thorac Oncol 2010;5:612–9.PubMedGoogle Scholar
  7. 7.
    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
  8. 8.
    Hodgson NC, Gulenchyn KY. Is there a role for positron emission tomography in breast cancer staging? J Clin Oncol 2008;26:712–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Aukema TS, Straver ME, Peeters MJ, Russell NS, Gilhuijs KG, Vogel WV, et al. Detection of extra-axillary lymph node involvement with FDG PET/CT in patients with stage II–III breast cancer. Eur J Cancer 2010;46:3205–10.PubMedCrossRefGoogle Scholar
  10. 10.
    Koolen BB, Vrancken Peeters MJ, Aukema TS, Vogel WV, Oldenburg HS, van der Hage JA, et al. 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;131:117–26.PubMedCrossRefGoogle Scholar
  11. 11.
    Aukema TS, Rutgers EJT, Vogel WV, Teertstra HJ, Oldenburg HS, Vrancken Peeters MT, et al. The role of FDG PET/CT in patients with locoregional breast cancer recurrence: a comparison to conventional imaging techniques. Eur J Surg Oncol 2010;36:387–92.PubMedCrossRefGoogle Scholar
  12. 12.
    Morris PG, Lynch C, Feeney JN, Patil S, Howard J, Larson SM, et al. Integrated positron emission tomography/computed tomography may render bone scintigraphy unnecessary to investigate suspected metastatic breast cancer. J Clin Oncol 2010;28:3154–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Groheux D, Giacchetti S, Espié M, Rubello D, Moretti JL, Hindié E. Early monitoring of response to neoadjuvant chemotherapy in breast cancer with 18F-FDG PET/CT: defining a clinical aim. Eur J Nucl Med Mol Imaging 2011;38:419–25.PubMedCrossRefGoogle Scholar
  14. 14.
    Schwarz-Dose J, Untch M, Tiling R, Sassen S, Mahner S, Kahlert S, et al. Monitoring primary systemic therapy of large and locally advanced breast cancer by using sequential positron emission tomography imaging with [18F]fluorodeoxyglucose. J Clin Oncol 2009;27:535–41.PubMedCrossRefGoogle Scholar
  15. 15.
    van Quarles Ufford HM, van Tinteren H, Stroobants SG, Riphagen II, Hoekstra OS. Added value of baseline 18F-FDG uptake in serial 18F-FDG PET for evaluation of response of solid extracerebral tumors to systemic cytotoxic neoadjuvant treatment: a meta-analysis. J Nucl Med 2010;51:1507–16.CrossRefGoogle Scholar
  16. 16.
    Groheux D, Giacchetti S, Moretti J-L, Porcher R, Espié M, Lehmann-Che J, et al. Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer. Eur J Nucl Med Mol Imaging 2011;38:426–35.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedCrossRefGoogle Scholar
  19. 19.
    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
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    Loo CE, Straver ME, Rodenhuis S, Muller SH, Wesseling J, Vrancken Peeters MJ, et al. Magnetic resonance imaging response monitoring of breast cancer during neoadjuvant chemotherapy: relevance of breast cancer subtype. J Clin Oncol 2011;29:660–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Vidal-Scart S, Aukema TS, Vogel WV, Hoefnagel CA, Valdés-Olmos RA. Added value of prone position technique for PET-TAC in breast cancer patients. Rev Esp Med Nucl 2010;29:230–5.CrossRefGoogle Scholar
  23. 23.
    Boellaard R, Oyen WJG, Hoekstra CJ, Hoekstra OS, Visser EP, Willemsen AT, et al. The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials. Eur J Nucl Med Mol Imaging 2008;35:2320–33.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    Lips EH, Mulder L, de Ronde JJ, Mandjes IA, Vincent A, Vrancken Peeters MT, et al. Neoadjuvant chemotherapy in ER+ HER2- breast cancer: response prediction based on immunohistochemical and molecular characteristics. Breast Cancer Res Treat 2012;131:827–36.PubMedCrossRefGoogle Scholar
  26. 26.
    Parker JS, Mullins M, Cheang MCU, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009;27:1160–7.PubMedCrossRefGoogle Scholar
  27. 27.
    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.PubMedCrossRefGoogle Scholar
  28. 28.
    Nakajo M, Kajiya Y, Kaneko T, Kaneko Y, Takasaki T, Tani A, et al. 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;37:2011–20.PubMedCrossRefGoogle Scholar
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    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.PubMedCrossRefGoogle Scholar
  31. 31.
    Henson DE, Chu KC, Levine PH. Histologic grade, stage, and survival in breast carcinoma: comparison of African American and Caucasian women. Cancer 2003;98:908–17.PubMedCrossRefGoogle Scholar
  32. 32.
    Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California Cancer Registry. Cancer 2007;109:1721–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Cristofanilli M, Gonzalez-Angulo A, Sneige N, Kau SW, Broglio K, Theriault RL, et al. Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. J Clin Oncol 2005;23:41–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 2006;24:5652–7.PubMedCrossRefGoogle Scholar
  35. 35.
    de Ronde JJ, Hannemann J, Halfwerk H, Mulder L, Straver ME, Vrancken Peeters MJ, et al. Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response. Breast Cancer Res Treat 2010;119:119–26.PubMedCrossRefGoogle Scholar
  36. 36.
    Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ, Decker T, Eusebi V, et al. Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res 2010;12:207.PubMedGoogle Scholar
  37. 37.
    Harris GC, Denley HE, Pinder SE, Lee AH, Ellis IO, Elston CW, et al. Correlation of histologic prognostic factors in core biopsies and therapeutic excisions of invasive breast carcinoma. Am J Surg Pathol 2003;27:11–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Fletcher JW, Djulbegovic B, Soares HP, Siegel BA, Lowe VJ, Lyman GH, et al. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med 2008;49:480–508.PubMedCrossRefGoogle Scholar
  39. 39.
    Straver ME, Rutgers EJT, Rodenhuis S, Linn SC, Loo CE, Wesseling J, et al. The relevance of breast cancer subtypes in the outcome of neoadjuvant chemotherapy. Ann Surg Oncol 2010;17:2411–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • B. B. Koolen
    • 1
    • 2
  • M. J. T. F. D. Vrancken Peeters
    • 2
  • J. Wesseling
    • 3
  • E. H. Lips
    • 3
  • W. V. Vogel
    • 1
  • T. S. Aukema
    • 1
    • 2
  • E. van Werkhoven
    • 4
  • K. G. A. Gilhuijs
    • 5
    • 7
  • S. Rodenhuis
    • 6
  • E. J. Th. Rutgers
    • 2
  • R. A. Valdés Olmos
    • 1
  1. 1.Department of Nuclear MedicineNetherlands Cancer Institute-Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  2. 2.Department of Surgical OncologyNetherlands Cancer Institute-Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  3. 3.Department of Pathology and Experimental TherapyNetherlands Cancer Institute-Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  4. 4.Department of BiometricsNetherlands Cancer Institute-Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  5. 5.Department of RadiologyNetherlands Cancer Institute-Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  6. 6.Department of Medical OncologyNetherlands Cancer Institute-Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  7. 7.Department of RadiologyUniversity Medical Centre UtrechtUtrechtThe Netherlands

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