[18F]FDG-PET predicts complete pathological response of breast cancer to neoadjuvant chemotherapy

  • Alina Berriolo-Riedinger
  • Claude Touzery
  • Jean-Marc Riedinger
  • Michel Toubeau
  • Bruno Coudert
  • Laurent Arnould
  • Christophe Boichot
  • Alexandre Cochet
  • Pierre Fumoleau
  • François Brunotte
Original Article

Abstract

Purpose

To evaluate, in breast cancer patients treated by neoadjuvant chemotherapy, the predictive value of reduction in FDG uptake with regard to complete pathological response (pCR).

Methods

Forty-seven women with non-metastatic, non-inflammatory, large or locally advanced breast cancer were included. Tumour uptake of FDG was evaluated before and after the first course of neoadjuvant chemotherapy. Four indices were used: maximal and average SUV without or with correction by body surface area and glycaemia (SUVmax, SUVavg, SUVmax-BSA-G and SUVavg-BSA-G, respectively). The predictive value of reduction in FDG uptake with respect to pCR was studied by logistic regression analysis. Relationships between baseline [18F]FDG uptake and prognostic parameters were assessed.

Results

The relative decrease in FDG uptake (ΔSUV) after the first course of neoadjuvant chemotherapy was significantly greater in the pCR group than in the non-pCR group (p < 0.000066). The four FDG uptake indices were all strongly correlated with each other. A decrease in SUVmax-BSA-G of 85.4% ± 21.9% was found in pCR patients, versus 22.6% ± 36.6% in non-pCR patients. ΔSUVmax-BSA-G <−60% predicted the pCR with an accuracy of 87% and ΔSUVs were found to be only factors predictive of the pCR at multivariate analysis. An elevated baseline SUV was associated with high mitotic activity (p < 0.0016), tumour grading (p < 0.004), high nuclear pleomorphism score (p < 0.03) and negative hormonal receptor status (p < 0.005).

Conclusion

In breast cancer patients, after only one course of neoadjuvant chemotherapy the reduction in FDG uptake is an early and powerful predictor of pCR.

Keywords

18F-fluorodeoxyglucose Breast cancer PET scan Monitoring therapy SUV 

References

  1. 1.
    Honkoop AH, van Diest PJ, de Jong JS, Linn SC, Giaccone G, Hoekman K, et al. Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer. Br J Cancer 1998;77:621–6.PubMedGoogle Scholar
  2. 2.
    Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg 1995;180:297–306.PubMedGoogle Scholar
  3. 3.
    Feldman LD, Hortobagyi GN, Buzdar AU, Ames FC, Blumenschein GR. Pathological assessment of response to induction chemotherapy in breast cancer. Cancer Res 1986;46:2578–81.PubMedGoogle Scholar
  4. 4.
    Machiavelli MR, Romero AO, Perez JE, Lacava JA, Dominguez ME, Rodriguez R, et al. Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma. Cancer J Sci Am 1998;4:125–31.PubMedGoogle Scholar
  5. 5.
    Heller W, Mazhar D, Ward R, Sinnett HD, Lowdell C, Phillips R, et al. Neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy followed by docetaxel in refractory patients with locally advanced breast cancer. Oncol Rep 2007;17:253–9.PubMedGoogle Scholar
  6. 6.
    Sarid D, Ron IG, Sperber F, Stadler Y, Kahan P, Kovner F, et al. Neoadjuvant treatment with paclitaxel and epirubicin in invasive breast cancer: a phase II study. Clin Drug Investig 2006;26:691–701.PubMedCrossRefGoogle Scholar
  7. 7.
    Dieras V, Fumoleau P, Romieu G, Tubiana-Hulin M, Namer M, Mauriac L, et al. Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer. J Clin Oncol 2004;22:4958–65.PubMedCrossRefGoogle Scholar
  8. 8.
    Warburg O, Wind F, Neglers E. On the metabolism of tumors in the body. In: Warburg O, editor. Metabolism of tumors. London: Constable; 1930. p. 264–70.Google Scholar
  9. 9.
    Baum RP, Przetak C. Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET). Q J Nucl Med 2001;45:257–68.PubMedGoogle Scholar
  10. 10.
    Erdi YE, Macapinlac H, Rosenzweig KE, Humm JL, Larson SM, Erdi AK, et al. Use of PET to monitor the response of lung cancer to radiation treatment. Eur J Nucl Med 2000;27:861–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Findlay M, Young H, Cunningham D, Iveson A, Cronin B, Hickish T, et al. Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil. J Clin Oncol 1996;14:700–8.PubMedGoogle Scholar
  12. 12.
    Gennari A, Donati S, Salvadori B, Giorgetti A, Salvadori PA, Sorace O, et al. Role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients. Clin Breast Cancer 2000;1:156–61.PubMedCrossRefGoogle Scholar
  13. 13.
    Wahl RL, Zasadny K, Helvie M, Hutchins GD, Weber B, Cody R. Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 1993;11:2101–11.PubMedGoogle Scholar
  14. 14.
    Schelling M, Avril N, Nahrig J, Kuhn W, Romer W, Sattler D, et al. Positron emission tomography using [18F]fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 2000;18:1689–95.PubMedGoogle Scholar
  15. 15.
    Kim SJ, Kim SK, Lee ES, Ro J, Kang S. Predictive value of [18F]FDG PET for pathological response of breast cancer to neo-adjuvant chemotherapy. Ann Oncol 2004;15:1352–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer 1999;35:1773–82.PubMedCrossRefGoogle Scholar
  17. 17.
    UICC. TNM classification of malignant tumours. Sobin LH, Wittekind C, editors. 2002.Google Scholar
  18. 18.
    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
  19. 19.
    Browne J, Depierro AR. A row-acting alternative to the EM algorithm for maximizing likelihoods in emission tomography. IEEE Trans Ed Imaging 1996;15:687–99.CrossRefGoogle Scholar
  20. 20.
    Adam LE, Karp JS, Daube-Witherspoon ME, Smith RJ. Performance of a whole-body PET scanner using curve-plate NaI(Tl) detectors. J Nucl Med 2001;42:1821–30.PubMedGoogle Scholar
  21. 21.
    Wahl RL, Cody RL, Hutchins GD, Mudgett EE. Primary and metastatic breast carcinoma: initial clinical evaluation with PET with the radiolabeled glucose analogue 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1991;179:765–70.PubMedGoogle Scholar
  22. 22.
    Kim CK, Gupta NC, Chandramouli B, Alavi A. Standardized uptake values of FDG: body surface area correction is preferable to body weight correction. J Nucl Med 1994;35:164–7.PubMedGoogle Scholar
  23. 23.
    Lindholm P, Minn H, Leskinen-Kallio S, Bergman J, Ruotsalainen U, Joensuu H. Influence of the blood glucose concentration on FDG uptake in cancer—a PET study. J Nucl Med 1993;34:1–6.PubMedGoogle Scholar
  24. 24.
    Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Int Med 1916;17:863–71.Google Scholar
  25. 25.
    Akashi-Tanaka S, Fukutomi T, Watanabe T, Katsumata N, Nanasawa T, Matsuo K, et al. Accuracy of contrast-enhanced computed tomography in the prediction of residual breast cancer after neoadjuvant chemotherapy. Int J Cancer 2001;96:66–73.PubMedCrossRefGoogle Scholar
  26. 26.
    Smith IC, Welch AE, Hutcheon AW, Miller ID, Payne S, Chilcott F, et al. Positron emission tomography using [18F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol 2000;18:1676–88.PubMedGoogle Scholar
  27. 27.
    Burcombe RJ, Makris A, Pittam M, Lowe J, Emmott J, Wong WL. Evaluation of good clinical response to neoadjuvant chemotherapy in primary breast cancer using [18F]-fluorodeoxyglucose positron emission tomography. Eur J Cancer 2002;38:375–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Rousseau C, Devillers A, Sagan C, Ferrer L, Bridji B, Campion L, et al. Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F]fluorodeoxyglucose positron emission tomography. J Clin Oncol 2006;24:5366–72.PubMedCrossRefGoogle Scholar
  29. 29.
    Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 2003;88:406–12.PubMedCrossRefGoogle Scholar
  30. 30.
    Burcombe RJ, Makris A, Richman PI, Daley FM, Noble S, Pittam M, et al. Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer. Br J Cancer 2005;92:147–55.PubMedCrossRefGoogle Scholar
  31. 31.
    Avril N, Sassen S, Schmalfeldt B, Naehrig J, Rutke S, Weber WA, et al. Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer. J Clin Oncol 2005;23:7445–53.PubMedCrossRefGoogle Scholar
  32. 32.
    Kostakoglu L, Agress H Jr, Goldsmith SJ. Clinical role of FDG PET in evaluation of cancer patients. Radiographics 2003;23:315–40.PubMedCrossRefGoogle Scholar
  33. 33.
    Eubank WB, Mankoff DA. Evolving role of positron emission tomography in breast cancer imaging. Semin Nucl Med 2005;35:84–99.PubMedCrossRefGoogle Scholar
  34. 34.
    Inoue T, Kim EE, Wallace S, Yang DJ, Wong FC, Bassa P, et al. Positron emission tomography using [18F]fluorotamoxifen to evaluate therapeutic responses in patients with breast cancer: preliminary study. Cancer Biother Radiopharm 1996;11:235–45.PubMedGoogle Scholar
  35. 35.
    Inoue T, Yutani K, Taguchi T, Tamaki Y, Shiba E, Noguchi S. Preoperative evaluation of prognosis in breast cancer patients by [18F]2-deoxy-2-fluoro-D-glucose-positron emission tomography. J Cancer Res Clin Oncol 2004;5:273–8.CrossRefGoogle Scholar
  36. 36.
    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
  37. 37.
    Buck A, Schirrmeister H, Kuhn 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
  38. 38.
    Erdi YE, Mawlawi O, Larson SM, Imbriaco M, Yeung H, Finn R, et al. Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding. Cancer 1997;80:2505–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Hickeson M, Yun M, Matthies A, Zhuang H, Adam LE, Lacorte L, et al. Use of a corrected standardized uptake value based on the lesion size on CT permits accurate characterization of lung nodules on FDG-PET. Eur J Nucl Med Mol Imaging 2002;29:1639–47.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Alina Berriolo-Riedinger
    • 1
    • 5
  • Claude Touzery
    • 1
  • Jean-Marc Riedinger
    • 1
  • Michel Toubeau
    • 1
  • Bruno Coudert
    • 2
  • Laurent Arnould
    • 3
  • Christophe Boichot
    • 1
  • Alexandre Cochet
    • 1
  • Pierre Fumoleau
    • 2
  • François Brunotte
    • 1
    • 4
  1. 1.Department of Nuclear MedicineCentre Georges Francois LeclercDijonFrance
  2. 2.Department of Medical OncologyCentre Georges Francois LeclercDijonFrance
  3. 3.Department of PathologyCentre Georges Francois LeclercDijonFrance
  4. 4.CNRS UMR 5158DijonFrance
  5. 5.1rue du Professeur MarionDijonFrance

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