Advertisement

HER2-positive breast cancer: 18F-FDG PET for early prediction of response to trastuzumab plus taxane-based neoadjuvant chemotherapy

  • Olivier HumbertEmail author
  • Alexandre Cochet
  • Jean-Marc Riedinger
  • Alina Berriolo-Riedinger
  • Laurent Arnould
  • Bruno Coudert
  • Isabelle Desmoulins
  • Michel Toubeau
  • Inna Dygai-Cochet
  • Séverine Guiu
  • Charles Coutant
  • Pierre Fumoleau
  • François Brunotte
Original Article

Abstract

Purpose

To investigate the value of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) to predict a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Material and methods

Fifty-seven consecutive women with HER2-positive breast cancer, treated with trastuzumab plus taxane-based NAC, were prospectively included. Maximum Standardized Uptake Value of the primary tumor and axillary nodes were measured at baseline (PET1.SUVmax) and after the first course of NAC (PET2.SUVmax). Tumor metabolic volumes were assessed to determine Total Lesion Glycolysis (TLG). The tumor metabolic response (ΔSUVmax and ΔTLG) was calculated.

Results

In univariate analysis, negative hormonal receptor status (p = 0.04), high tumor grade (p = 0.03), and low tumor PET 2 .SUVmax (p = 0.001) were predictive of pCR. Tumor ΔSUVmax correlated with pCR (p = 0.03), provided that tumors with low metabolic activity at baseline were excluded. ΔTLG did not correlate with pCR. In multivariate analysis, tumor PET2.SUVmax < 2.1 was the best independent predictive factor (Odds ratio =14.3; p = 0.004) with both negative and positive predictive values of 76 %. Although the metabolic features of the primary tumor did not depend on hormonal receptor status, both the baseline metabolism and early response of axillary nodes were higher if estrogen receptors were not expressed (p = 0.01 and p = 0.03, respectively).

Conclusion

In HER2-positive breast cancer, very low tumor residual metabolism after the first cycle of NAC (SUVmax < 2.1) was the main predictor of pCR. These results should be further explored in multicenter studies and incorporated into the design of clinical trials.

Keywords

Breast cancer Neoadjuvant chemotherapy PET HER2 Response monitoring 

Notes

Acknowledgments

This study is part of the PharmImage® project. We thank Mr Bastable for proof-reading the text.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Gralow JR, Burstein HJ, Wood W, Hortobagyi GN, Gianni L, von MG, et al. Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol. 2008;26:814–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15:2483–93.PubMedGoogle Scholar
  3. 3.
    Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005;97:188–94.PubMedCrossRefGoogle Scholar
  4. 4.
    Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17:460–9.PubMedGoogle Scholar
  5. 5.
    Perou CM, Sorlie T, Eisen MB, van de RM, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedCrossRefGoogle Scholar
  6. 6.
    Sorlie 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.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003;100:8418–23.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23:3676–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375:377–84.PubMedCrossRefGoogle Scholar
  10. 10.
    von MG, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRefGoogle Scholar
  11. 11.
    Vaz-Luis I, Ottesen RA, Hughes ME, Marcom PK, Moy B, Rugo HS, et al. Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study. Breast Cancer Res. 2012;14:R129.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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
  14. 14.
    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
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedCrossRefGoogle Scholar
  17. 17.
    Groheux D, Giacchetti S, Hatt M, Marty M, Vercellino L, de RA, 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.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedCrossRefGoogle Scholar
  19. 19.
    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. C. W. Elston & I. O. Ellis. Histopathology. 1991; 19; 403–410. Histopathology. 2002; 41:151–2, discussion.Google Scholar
  20. 20.
    Zafrani B, Aubriot MH, Mouret E, De CP, De RY, 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.PubMedCrossRefGoogle Scholar
  21. 21.
    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. J Clin Oncol. 2007;25:118–45.PubMedCrossRefGoogle Scholar
  22. 22.
    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
  23. 23.
    McDermott GM, Welch A, Staff RT, Gilbert FJ, Schweiger L, Semple SI, et al. Monitoring primary breast cancer throughout chemotherapy using FDG-PET. Breast Cancer Res Treat. 2007;102:75–84.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Hatt M, Groheux D, Martineau A, Espie M, Hindie 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.PubMedCrossRefGoogle Scholar
  26. 26.
    Barrington SF, Qian W, Somer EJ, Franceschetto A, Bagni B, Brun E, et al. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging. 2010;37:1824–33.PubMedCrossRefGoogle Scholar
  27. 27.
    Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011;29:4491–7.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Heim S, Teixeira MR, Dietrich CU, Pandis N. Cytogenetic polyclonality in tumors of the breast. Cancer Genet Cytogenet. 1997;95:16–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Teixeira MR, Pandis N, Bardi G, Andersen JA, Heim S. Karyotypic comparisons of multiple tumorous and macroscopically normal surrounding tissue samples from patients with breast cancer. Cancer Res. 1996;56:855–9.PubMedGoogle Scholar
  30. 30.
    Gluck S, Arteaga CL, Osborne CK. Optimizing chemotherapy-free survival for the ER/HER2-positive metastatic breast cancer patient. Clin Cancer Res. 2011;17:5559–61.PubMedCrossRefGoogle Scholar
  31. 31.
    Groheux D, Giacchetti S, Moretti JL, Porcher R, Espie 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.PubMedCrossRefGoogle Scholar
  32. 32.
    Dunnwald LK, Doot RK, Specht JM, Gralow JR, Ellis GK, Livingston RB, et al. PET tumor metabolism in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy: value of static versus kinetic measures of fluorodeoxyglucose uptake. Clin Cancer Res. 2011;17:2400–9.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Gebhart G, Gamez C, Holmes E, Robles J, Garcia C, Cortes 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. doi: 10.2967/112.119271.PubMedGoogle Scholar
  34. 34.
    Boellaard R. Standards for PET image acquisition and quantitative data analysis. J Nucl Med. 2009;50 Suppl 1:11S–20S.PubMedCrossRefGoogle Scholar
  35. 35.
    Boellaard R. Need for standardization of 18F-FDG PET/CT for treatment response assessments. J Nucl Med. 2011;52 Suppl 2:93S–100S.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Olivier Humbert
    • 1
    • 5
    • 6
    Email author
  • Alexandre Cochet
    • 1
    • 6
  • Jean-Marc Riedinger
    • 1
    • 2
  • Alina Berriolo-Riedinger
    • 1
  • Laurent Arnould
    • 2
  • Bruno Coudert
    • 3
  • Isabelle Desmoulins
    • 3
  • Michel Toubeau
    • 1
  • Inna Dygai-Cochet
    • 1
  • Séverine Guiu
    • 3
  • Charles Coutant
    • 4
  • Pierre Fumoleau
    • 3
  • François Brunotte
    • 1
    • 5
    • 6
  1. 1.Department of Nuclear MedicineCentre GF LeclercDijonFrance
  2. 2.Department of Biology and PathologyCentre GF LeclercDijonFrance
  3. 3.Department of Medical OncologyCentre GF LeclercDijonFrance
  4. 4.Department of SurgeryCentre GF LeclercDijonFrance
  5. 5.Imaging DepartmentCHU Le BocageDijonFrance
  6. 6.Université de Bourgogne, UMR CNRS 5158DijonFrance

Personalised recommendations