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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 8/2018

04.04.2018 | Original Article

Tumor metabolism assessed by FDG-PET/CT and tumor proliferation assessed by genomic grade index to predict response to neoadjuvant chemotherapy in triple negative breast cancer

verfasst von: David Groheux, L. Biard, J. Lehmann-Che, L. Teixeira, F. A. Bouhidel, B. Poirot, P. Bertheau, P. Merlet, M. Espié, M. Resche-Rigon, C. Sotiriou, P. de Cremoux

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 8/2018

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Abstract

Purpose

Survival is increased when pathological complete response (pCR) is reached after neoadjuvant chemotherapy (NAC), especially in triple-negative breast cancer (TNBC) patients. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) and the genomic grade index (GGI), each separately, showed good potential to predict pCR. Our study was designed to evaluate the predictive value for the therapeutic response of a combination of parameters based on FDG-PET, histoclinical features and molecular markers of proliferation.

Methods

Molecular parameters were measured on pre-treatment biopsy. Tumor metabolic activity was measured using two PET/CT scans, one before and one after 2 cycles of NAC. The pCR was determined on specimen after NAC. Event-free survival (EFS) was estimated using the Kaplan Meier method.

Results

Of 55 TNBC patients, 19 (35%) reached pCR after NAC. Tumor grade and Ki67 were not associated with pCR whereas GGI (P = 0.04) and its component KPNA2 (P = 0.04) showed a predictive value. The change of FDG uptake between PET1 and PET2 (ΔSUVmax) was highly associated with pCR (P = 0.0001) but the absolute value of baseline SUVmax was not (P = 0.11). However, the AUC of pCR prediction increased from 0.63 to 0.76 when baseline SUVmax was combined with the GGI (P = 0.016). The only two parameters associated with EFS were ΔSUVmax (P = 0.048) and pathological response (P = 0.014).

Conclusions

The early tumor metabolic change during NAC is a powerful parameter to predict pCR and outcome in TNBC patients. The GGI, determined on pretreatment biopsy, is also predictive of pCR and the combination GGI and baseline SUVmax improves the prediction.
Literatur
1.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
2.
Zurück zum Zitat Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006;98:262–72.CrossRefPubMed Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006;98:262–72.CrossRefPubMed
3.
Zurück zum Zitat Liedtke C, Hatzis C, Symmans WF, Desmedt C, Haibe-Kains B, Valero V, et al. Genomic grade index is associated with response to chemotherapy in patients with breast cancer. J Clin Oncol. 2009;27:3185–91.CrossRefPubMedPubMedCentral Liedtke C, Hatzis C, Symmans WF, Desmedt C, Haibe-Kains B, Valero V, et al. Genomic grade index is associated with response to chemotherapy in patients with breast cancer. J Clin Oncol. 2009;27:3185–91.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Bertucci F, Finetti P, Roche H, Le Doussal JM, Marisa L, Martin AL, et al. Comparison of the prognostic value of genomic grade index, Ki67 expression and mitotic activity index in early node-positive breast cancer patients. Ann Oncol. 2013;24:625–32.CrossRefPubMed Bertucci F, Finetti P, Roche H, Le Doussal JM, Marisa L, Martin AL, et al. Comparison of the prognostic value of genomic grade index, Ki67 expression and mitotic activity index in early node-positive breast cancer patients. Ann Oncol. 2013;24:625–32.CrossRefPubMed
5.
Zurück zum Zitat Toussaint J, Sieuwerts AM, Haibe-Kains B, Desmedt C, Rouas G, Harris AL, et al. Improvement of the clinical applicability of the genomic grade index through a qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded tissues. BMC Genomics. 2009;10:424.CrossRefPubMedPubMedCentral Toussaint J, Sieuwerts AM, Haibe-Kains B, Desmedt C, Rouas G, Harris AL, et al. Improvement of the clinical applicability of the genomic grade index through a qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded tissues. BMC Genomics. 2009;10:424.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Wang Y, Zhang C, Liu J, Huang G. Is 18F-FDG PET accurate to predict neoadjuvant therapy response in breast cancer? A Meta-Anal Breast Cancer Res Treat. 2012;131:357–69.CrossRefPubMed Wang Y, Zhang C, Liu J, Huang G. Is 18F-FDG PET accurate to predict neoadjuvant therapy response in breast cancer? A Meta-Anal Breast Cancer Res Treat. 2012;131:357–69.CrossRefPubMed
7.
Zurück zum Zitat Groheux D, Mankoff D, Espié M, Hindié E. (18)F-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. 2016;43:983–93.CrossRefPubMed Groheux D, Mankoff D, Espié M, Hindié E. (18)F-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. 2016;43:983–93.CrossRefPubMed
8.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
9.
Zurück zum Zitat Humbert O, Riedinger J-M, 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. Humbert O, Riedinger J-M, 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.
10.
Zurück zum Zitat Groheux D, Biard L, Giacchetti S, Teixeira L, Hindié E, Cuvier C, et al. 18F-FDG PET/CT for the early evaluation of response to neoadjuvant treatment in triple-negative breast Cancer: influence of the chemotherapy regimen. J Nucl Med. 2016;57:536–43.CrossRefPubMed Groheux D, Biard L, Giacchetti S, Teixeira L, Hindié E, Cuvier C, et al. 18F-FDG PET/CT for the early evaluation of response to neoadjuvant treatment in triple-negative breast Cancer: influence of the chemotherapy regimen. J Nucl Med. 2016;57:536–43.CrossRefPubMed
11.
Zurück zum Zitat Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn H-J, et al. Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast Cancer 2011. Ann Oncol. 2011;22:1736–47.CrossRefPubMedPubMedCentral Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn H-J, et al. Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast Cancer 2011. Ann Oncol. 2011;22:1736–47.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast Cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedPubMedCentral Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast Cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Denkert C, Loibl S, Müller BM, Eidtmann H, Schmitt WD, Eiermann W, et al. Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol. 2013;24:2786–93.CrossRefPubMed Denkert C, Loibl S, Müller BM, Eidtmann H, Schmitt WD, Eiermann W, et al. Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol. 2013;24:2786–93.CrossRefPubMed
14.
Zurück zum Zitat Hao S, He Z-X, Yu K-D, Yang W-T, Shao Z-M. New insights into the prognostic value of Ki-67 labeling index in patients with triple-negative breast cancer. Oncotarget. 2016;7:24824–31.PubMedPubMedCentral Hao S, He Z-X, Yu K-D, Yang W-T, Shao Z-M. New insights into the prognostic value of Ki-67 labeling index in patients with triple-negative breast cancer. Oncotarget. 2016;7:24824–31.PubMedPubMedCentral
15.
Zurück zum Zitat Royston P, Altman DG. Visualizing and assessing discrimination in the logistic regression model. Stat Med. 2010;29:2508–20.CrossRefPubMed Royston P, Altman DG. Visualizing and assessing discrimination in the logistic regression model. Stat Med. 2010;29:2508–20.CrossRefPubMed
16.
Zurück zum Zitat Koolen BB, Pengel KE, Wesseling J, Vogel WV, Vrancken Peeters M-JTFD, 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.CrossRefPubMed Koolen BB, Pengel KE, Wesseling J, Vogel WV, Vrancken Peeters M-JTFD, 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.CrossRefPubMed
17.
Zurück zum Zitat Groheux D, Hindié E, Delord M, Giacchetti S, Hamy A-S, de Bazelaire C, et al. Prognostic impact of 18FDG-PET-CT findings in clinical stage III and IIB breast Cancer. J Natl Cancer Inst. 2012;104:1879–87.CrossRefPubMedPubMedCentral Groheux D, Hindié E, Delord M, Giacchetti S, Hamy A-S, de Bazelaire C, et al. Prognostic impact of 18FDG-PET-CT findings in clinical stage III and IIB breast Cancer. J Natl Cancer Inst. 2012;104:1879–87.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Ohno S, Chow LWC, Sato N, Masuda N, Sasano H, Takahashi F, et al. Randomized trial of preoperative docetaxel with or without capecitabine after 4 cycles of 5-fluorouracil– epirubicin–cyclophosphamide (FEC) in early-stage breast cancer: exploratory analyses identify Ki67 as a predictive biomarker for response to neoadjuvant chemotherapy. Breast Cancer Res Treat. 2013;142:69–80.CrossRefPubMedPubMedCentral Ohno S, Chow LWC, Sato N, Masuda N, Sasano H, Takahashi F, et al. Randomized trial of preoperative docetaxel with or without capecitabine after 4 cycles of 5-fluorouracil– epirubicin–cyclophosphamide (FEC) in early-stage breast cancer: exploratory analyses identify Ki67 as a predictive biomarker for response to neoadjuvant chemotherapy. Breast Cancer Res Treat. 2013;142:69–80.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Besusparis J, Plancoulaine B, Rasmusson A, Augulis R, Green AR, Ellis IO, et al. Impact of tissue sampling on accuracy of Ki67 immunohistochemistry evaluation in breast cancer. Diagn Pathol. 2016;11:82.CrossRefPubMedPubMedCentral Besusparis J, Plancoulaine B, Rasmusson A, Augulis R, Green AR, Ellis IO, et al. Impact of tissue sampling on accuracy of Ki67 immunohistochemistry evaluation in breast cancer. Diagn Pathol. 2016;11:82.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Abubakar M, Orr N, Daley F, Coulson P, Ali HR, Blows F, et al. Prognostic value of automated KI67 scoring in breast cancer: a centralised evaluation of 8088 patients from 10 study groups. Breast Cancer Res. 2016;18:104.CrossRefPubMedPubMedCentral Abubakar M, Orr N, Daley F, Coulson P, Ali HR, Blows F, et al. Prognostic value of automated KI67 scoring in breast cancer: a centralised evaluation of 8088 patients from 10 study groups. Breast Cancer Res. 2016;18:104.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Ignatiadis M, Singhal SK, Desmedt C, Haibe-Kains B, Criscitiello C, Andre F, et al. Gene modules and response to neoadjuvant chemotherapy in breast cancer subtypes: a pooled analysis. J Clin Oncol. 2012;30:1996–2004.CrossRefPubMed Ignatiadis M, Singhal SK, Desmedt C, Haibe-Kains B, Criscitiello C, Andre F, et al. Gene modules and response to neoadjuvant chemotherapy in breast cancer subtypes: a pooled analysis. J Clin Oncol. 2012;30:1996–2004.CrossRefPubMed
Metadaten
Titel
Tumor metabolism assessed by FDG-PET/CT and tumor proliferation assessed by genomic grade index to predict response to neoadjuvant chemotherapy in triple negative breast cancer
verfasst von
David Groheux
L. Biard
J. Lehmann-Che
L. Teixeira
F. A. Bouhidel
B. Poirot
P. Bertheau
P. Merlet
M. Espié
M. Resche-Rigon
C. Sotiriou
P. de Cremoux
Publikationsdatum
04.04.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 8/2018
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-018-3998-z

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