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18F-FDG PET/CT in the early prediction of pathological response in aggressive subtypes of breast cancer: review of the literature and recommendations for use in clinical trials

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Abstract

Early assessment of response to neoadjuvant chemotherapy (NAC) might be helpful in avoiding the toxicity of ineffective chemotherapy and allowing refinement of treatment. We conducted a review of the literature regarding the applicability of 18F-FDG PET/CT to the prediction of an early pathological response in different subgroups of breast cancer. Clinical research in this field has intensified in the last few years. Early studies by various groups have shown the potential of 18F-FDG PET/CT in the early assessment of response to NAC. However, interim PET/CT in breast cancer has not yet gained wide acceptance compared to its use in other settings such as lymphomas. This is in part due to a lack of consensus that early evaluation of response can be used to direct change in therapy in the neoadjuvant breast cancer setting, and only limited data showing that response-adaptive therapy leads to improved outcomes. However, one major element that has hampered the use of 18F-FDG PET/CT in directing neoadjuvant therapy is its evaluation in populations with mixed subtypes of breast cancer. However, major improvements have occurred in recent years. Pilot studies have highlighted the need for considering breast cancer subtype and the type of treatment, and have offered criteria for the use of PET/CT for the early prediction of response in specific settings. 18F-FDG PET/CT has considerable potential for the early prediction of pathological complete response to NAC in aggressive subtypes such as triple-negative or HER2-positive breast cancers. The results of a multicentre trial that used early metabolic response on 18F-FDG PET/CT as a means to select poor responders to adapt neoadjuvant treatment have recently been published. Other trials are ongoing or being planned.

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References

  1. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 1. 2016. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.

  2. Gralow JR, Burstein HJ, Wood W, Hortobagyi GN, Gianni L, von Minckwitz G, et al. Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol. 2008;26:814–9.

    Article  PubMed  Google Scholar 

  3. Smith IC, Welch AE, Hutcheon AW, Miller ID, Payne S, Chilcott F, et al. Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol. 2000;18:1676–88.

    CAS  PubMed  Google Scholar 

  4. Schelling M, Avril N, Nährig J, Kuhn W, Römer W, Sattler D, et al. Positron emission tomography using [(18)F]Fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol. 2000;18:1689–95.

    CAS  PubMed  Google Scholar 

  5. Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Schubert EK, Tseng J, et al. Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy. J Nucl Med. 2003;44:1806–14.

    PubMed  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. Berriolo-Riedinger A, Touzery C, Riedinger J-M, 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.

    Article  CAS  PubMed  Google Scholar 

  8. McDermott GM, Welch A, Staff RT, Gilbert FJ, Schweiger L, Semple SIK, et al. Monitoring primary breast cancer throughout chemotherapy using FDG-PET. Breast Cancer Res Treat. 2007;102:75–84.

    Article  CAS  PubMed  Google Scholar 

  9. Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Specht JM, et al. Tumor metabolism and blood flow changes by positron emission tomography: relation to survival in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. J Clin Oncol. 2008;26:4449–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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.

    Article  PubMed  Google Scholar 

  11. Kumar A, Kumar R, Seenu V, Gupta SD, Chawla M, Malhotra A, et al. The role of 18F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Eur Radiol. 2009;19:1347–57.

    Article  PubMed  Google Scholar 

  12. Duch J, Fuster D, Muñoz M, Fernández PL, Paredes P, Fontanillas M, et al. 18F-FDG PET/CT for early prediction of response to neoadjuvant chemotherapy in breast cancer. Eur J Nucl Med Mol Imaging. 2009;36:1551–7.

    Article  CAS  PubMed  Google Scholar 

  13. Schneider-Kolsky ME, Hart S, Fox J, Midolo P, Stuckey J, Hofman M, et al. The role of chemotherapeutic drugs in the evaluation of breast tumour response to chemotherapy using serial FDG-PET. Breast Cancer Res. 2010;12:R37.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wang Y, Zhang C, Liu J, Huang G. Is 18F-FDG PET accurate to predict neoadjuvant therapy response in breast cancer? A meta-analysis. Breast Cancer Res Treat. 2012;131:357–69.

    Article  CAS  PubMed  Google Scholar 

  15. Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Müeller SP, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32:3048–58.

    Article  PubMed  Google Scholar 

  16. Bardia A, Baselga J. Neoadjuvant therapy as a platform for drug development and approval in breast cancer. Clin Cancer Res. 2013;19:6360–70.

    Article  CAS  PubMed  Google Scholar 

  17. Rigter LS, Loo CE, Linn SC, Sonke GS, van Werkhoven E, Lips EH, et al. Neoadjuvant chemotherapy adaptation and serial MRI response monitoring in ER-positive HER2-negative breast cancer. Br J Cancer. 2013;109:2965–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Coudert B, Pierga J-Y, Mouret-Reynier M-A, Kerrou K, Ferrero J-M, Petit T, et al. Use of [(18)F]-FDG PET to predict response to neoadjuvant trastuzumab and docetaxel in patients with HER2-positive breast cancer, and addition of bevacizumab to neoadjuvant trastuzumab and docetaxel in [(18)F]-FDG PET-predicted non-responders (AVATAXHER): an open-label, randomised phase 2 trial. Lancet Oncol. 2014;15:1493–502.

    Article  CAS  PubMed  Google Scholar 

  19. Bos R, van Der Hoeven JJM, van Der Wall E, van Der Groep P, van Diest PJ, Comans EFI, et al. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol. 2002;20:379–87.

    Article  CAS  PubMed  Google Scholar 

  20. Specht JM, Kurland BF, Montgomery SK, Dunnwald LK, Doot RK, Gralow JR, et al. Tumor metabolism and blood flow as assessed by positron emission tomography varies by tumor subtype in locally advanced breast cancer. Clin Cancer Res. 2010;16:2803–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Groheux D, Giacchetti S, Espié M, Rubello D, Moretti J-L, Hindié E. Early monitoring of response to neoadjuvant chemotherapy in breast cancer with (18)F-FDG PET/CT: defining a clinical aim. Eur J Nucl Med Mol Imaging. 2011;38:419–25.

    Article  PubMed  Google Scholar 

  22. Groheux D, Majdoub M, Sanna A, de Cremoux P, Hindié E, Giacchetti S, et al. Early metabolic response to neoadjuvant treatment: FDG PET/CT criteria according to breast cancer subtype. Radiology. 2015;277:358–71.

    Article  PubMed  Google Scholar 

  23. Groheux D, Hindié E, Giacchetti S, Delord M, Hamy A-S, de Roquancourt A, et al. Triple-negative breast cancer: early assessment with 18F-FDG PET/CT during neoadjuvant chemotherapy identifies patients who are unlikely to achieve a pathologic complete response and are at a high risk of early relapse. J Nucl Med. 2012;53:249–54.

    Article  CAS  PubMed  Google Scholar 

  24. Humbert O, Berriolo-Riedinger A, Riedinger JM, Coudert B, Arnould L, Cochet A, et al. Changes in 18F-FDG tumor metabolism after a first course of neoadjuvant chemotherapy in breast cancer: influence of tumor subtypes. Ann Oncol. 2012;23:2572–7.

    Article  CAS  PubMed  Google Scholar 

  25. Zucchini G, Quercia S, Zamagni C, Santini D, Taffurelli M, Fanti S, et al. Potential utility of early metabolic response by 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography in a selected group of breast cancer patients receiving preoperative chemotherapy. Eur J Cancer. 2013;49:1539–45.

    Article  CAS  PubMed  Google Scholar 

  26. Groheux D, Hatt M, Hindié E, Giacchetti S, de Cremoux P, Lehmann-Che J, et al. Estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast tumors: early prediction of chemosensitivity with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography during neoadjuvant chemotherapy. Cancer. 2013;119:1960–8.

    Article  CAS  PubMed  Google Scholar 

  27. Groheux D, Giacchetti S, Hatt M, Marty M, Vercellino L, de Roquancourt A, et al. HER2-overexpressing breast cancer: FDG uptake after two cycles of chemotherapy predicts the outcome of neoadjuvant treatment. Br J Cancer. 2013;109:1157–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Koolen BB, Pengel KE, Wesseling J, Vogel WV, Vrancken Peeters MJ, Vincent AD, et al. FDG PET/CT during neoadjuvant chemotherapy may predict response in ER-positive/HER2-negative and triple negative, but not in HER2-positive breast cancer. Breast. 2013;22:691–7.

    Article  PubMed  Google Scholar 

  29. Gebhart G, Gámez C, Holmes E, Robles J, Garcia C, Cortés M, et al. 18F-FDG PET/CT for early prediction of response to neoadjuvant lapatinib, trastuzumab, and their combination in HER2-positive breast cancer: results from Neo-ALTTO. J Nucl Med. 2013;54:1862–8.

    Article  CAS  PubMed  Google Scholar 

  30. Koolen BB, Pengel KE, Wesseling J, Vogel WV, Vrancken Peeters MJ, Vincent AD, et al. Sequential (18)F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging. 2014;41:32–40.

    Article  CAS  PubMed  Google Scholar 

  31. Groheux D, Hindié E, Giacchetti S, Hamy A-S, Berger F, Merlet P, et al. Early assessment with 18F-fluorodeoxyglucose positron emission tomography/computed tomography can help predict the outcome of neoadjuvant chemotherapy in triple negative breast cancer. Eur J Cancer. 2014;50:1864–71.

    Article  PubMed  Google Scholar 

  32. Humbert O, Berriolo-Riedinger A, Cochet A, Gauthier M, Charon-Barra C, Guiu S, et al. Prognostic relevance at 5 years of the early monitoring of neoadjuvant chemotherapy using (18)F-FDG PET in luminal HER2-negative breast cancer. Eur J Nucl Med Mol Imaging. 2014;41:416–27.

    Article  CAS  PubMed  Google Scholar 

  33. Humbert O, Cochet A, Riedinger J-M, Berriolo-Riedinger A, Arnould L, Coudert B, et al. HER2-positive breast cancer: 18F-FDG PET for early prediction of response to trastuzumab plus taxane-based neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging. 2014;41:1525–33.

    Article  CAS  PubMed  Google Scholar 

  34. Connolly RM, Leal JP, Goetz MP, Zhang Z, Zhou XC, Jacobs LK, et al. TBCRC 008: early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer. J Nucl Med. 2015;56:31–7.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Groheux D, Sanna A, Majdoub M, de Cremoux P, Giacchetti S, Teixeira L, et al. Baseline tumor 18F-FDG uptake and modifications after 2 cycles of neoadjuvant chemotherapy are prognostic of outcome in ER+/HER2- breast cancer. J Nucl Med. 2015;56:824–31.

    Article  CAS  PubMed  Google Scholar 

  36. Humbert O, Riedinger JM, Charon-Barra C, Berriolo-Riedinger A, Desmoulins I, Lorgis V, et al. Identification of biomarkers including 18FDG-PET/CT for early prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer. Clin Cancer Res. 2015;21:5460–8.

    Article  CAS  PubMed  Google Scholar 

  37. Groheux D, Biard L, Giacchetti S, Teixeira L, Hindié E Cuvier L, et al. 18FDG-PET/CT for the early evaluation of response to neoadjuvant treatment in triple negative breast cancer: influence of the chemotherapy regimen. J Nucl Med. 2015. doi:10.2967/jnumed.115.163907.

  38. 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.

    CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. Groheux D, Giacchetti S, Moretti J-L, Porcher R, Espié M, Lehmann-Che J, et al. Correlation of high (18)F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer. Eur J Nucl Med Mol Imaging. 2011;38:426–35.

    Article  PubMed  Google Scholar 

  41. 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.

    Article  CAS  PubMed  Google Scholar 

  42. Alvarez JV, Belka GK, Pan T-C, Chen C-C, Blankemeyer E, Alavi A, et al. Oncogene pathway activation in mammary tumors dictates FDG-PET uptake. Cancer Res. 2014;74:7583–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.

    Article  PubMed  Google Scholar 

  44. Groheux D. Predicting pathological complete response in breast cancer early. Lancet Oncol. 2014;15:1415–6.

    Article  PubMed  Google Scholar 

  45. Tateishi U, Miyake M, Nagaoka T, Terauchi T, Kubota K, Kinoshita T, et al. Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging – prospective assessment. Radiology. 2012;263:53–63.

    Article  PubMed  Google Scholar 

  46. Hatt M, Groheux D, Martineau A, Espié M, Hindié E, Giacchetti S, et al. Comparison between 18F-FDG PET image-derived indices for early prediction of response to neoadjuvant chemotherapy in breast cancer. J Nucl Med. 2013;54:341–9.

    Article  CAS  PubMed  Google Scholar 

  47. Doot RK, Dunnwald LK, Schubert EK, Muzi M, Peterson LM, Kinahan PE, et al. Dynamic and static approaches to quantifying 18F-FDG uptake for measuring cancer response to therapy, including the effect of granulocyte CSF. J Nucl Med. 2007;48:920–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.

    Article  CAS  PubMed  Google Scholar 

  49. Untch M, Fasching PA, Konecny GE, Hasmüller S, Lebeau A, Kreienberg R, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011;29:3351–7.

    Article  CAS  PubMed  Google Scholar 

  50. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379:633–40.

    Article  CAS  PubMed  Google Scholar 

  51. Gianni L, Pienkowski T, Im Y-H, Roman L, Tseng L-M, Liu M-C, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25–32.

    Article  CAS  PubMed  Google Scholar 

  52. Cheng J, Wang Y, Mo M, Bao X, Zhang Y, Liu G, et al. 18F-fluorodeoxyglucose (FDG) PET/CT after two cycles of neoadjuvant therapy may predict response in HER2-negative, but not in HER2-positive breast cancer. Oncotarget. 2015;6:29388–95.

  53. García Vicente AM, Soriano Castrejón A, León Martín A, Relea Calatayud F, Muñoz Sánchez MDM, Cruz Mora MA, et al. Early and delayed prediction of axillary lymph node neoadjuvant response by (18)F-FDG PET/CT in patients with locally advanced breast cancer. Eur J Nucl Med Mol Imaging. 2014;41:1309–18.

    Article  PubMed  Google Scholar 

  54. Groheux D, Majdoub M, Tixier F, Le Rest CC, Martineau A, Merlet P, et al. Do clinical, histological or immunohistochemical primary tumour characteristics translate into different (18)F-FDG PET/CT volumetric and heterogeneity features in stage II/III breast cancer? Eur J Nucl Med Mol Imaging. 2015;42:1682–91.

    Article  CAS  PubMed  Google Scholar 

  55. Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Delbeke D, Coleman RE, Guiberteau MJ, Brown ML, Royal HD, Siegel BA, et al. Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J Nucl Med. 2006;47:885–95.

    PubMed  Google Scholar 

  57. Hindié E, Groheux D. Pathological complete response in breast cancer. Lancet. 2015;385:114.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nuclear Medicine, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France

    David Groheux

  2. University Paris-Diderot, PRES Paris Cité, INSERM/CNRS UMR944/7212, Paris, France

    David Groheux & Marc Espié

  3. Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA

    David Mankoff

  4. Department of Medical Oncology, Breast Diseases Centre, Saint-Louis Hospital, Paris, France

    Marc Espié

  5. Department of Nuclear Medicine, Haut-Lévêque Hospital, University of Bordeaux, Bordeaux, France

    Elif Hindié

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  1. David Groheux
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Correspondence to David Groheux.

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Groheux, D., Mankoff, D., Espié, M. et al. 18F-FDG PET/CT in the early prediction of pathological response in aggressive subtypes of breast cancer: review of the literature and recommendations for use in clinical trials. Eur J Nucl Med Mol Imaging 43, 983–993 (2016). https://doi.org/10.1007/s00259-015-3295-z

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