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Published in: Pathology & Oncology Research 2/2020

Open Access 01-04-2020 | Breast Cancer | Original Article

Dynamic FDG-PET/CT in the Initial Staging of Primary Breast Cancer: Clinicopathological Correlations

Authors: Kornélia Kajáry, Zsolt Lengyel, Anna-Mária Tőkés, Janina Kulka, Magdolna Dank, Tímea Tőkés

Published in: Pathology & Oncology Research | Issue 2/2020

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Abstract

Our aim was to evaluate correlation between clinicopathological features (clinical T and clinical N stages; histological type; nuclear grade; hormone-receptor and HER2 status, proliferation activity and tumor subtypes) of breast cancer and kinetic parameters measured by staging dynamic FDG-PET/CT examinations. Following ethical approval and patients’ informed consent we included 34 patients with 35 primary breast cancers in our prospective study. We performed dynamic PET imaging, and assessed plasma activity noninvasively. To delineate primary tumors we applied a frame-by-frame semi-automatic software-based correction of motion artefacts. FDG two-compartment kinetic modelling was applied to assess K1, k2, k3 rate coefficients and to calculate Ki (tracer flux constant) and MRFDG (FDG metabolic rate). We found that k3, Ki and MRFDG were significantly higher in higher grade (p = 0.0246, 0.0089 and 0.0076, respectively), progesterone-receptor negative (p = 0.0344, 0.0217 and 0.0132) and highly-proliferating (p = 0.0414, 0.0193 and 0.0271) tumors as well as in triple-negative and hormone-receptor negative/HER2-positive subtypes (p = 0.0310, 0.0280 and 0.0186). Ki and MRFDG were significantly higher in estrogen-receptor negative tumors (p = 0.0300 and 0.0247, respectively). Ki was significantly higher in node-positive than in node-negative disease (p = 0.0315). None of the assessed FDG-kinetic parameters showed significant correlation with stromal TIL. In conclusion, we confirmed a significant relationship between kinetic parameters measured by dynamic PET and the routinely assessed clinicopathological factors of breast cancer: high-grade, hormone-receptor negative tumors with high proliferation rate are characterized by higher cellular FDG-uptake and FDG-phosphorylation rate. Furthermore, we found that kinetic parameters based on the dynamic examinations are probably not influenced by stromal TIL infiltration.
Literature
1.
go back to reference International Atomic Energy Agency (2013) Standard operation procedures for PET/CT: a practical approach for use in adult oncology. IAEA Human Health Series No.26, Vienna International Atomic Energy Agency (2013) Standard operation procedures for PET/CT: a practical approach for use in adult oncology. IAEA Human Health Series No.26, Vienna
2.
go back to reference Groheux D, Espie M, Giacchetti S, Hindie E (2013) Performance of FDG PET/CT in the clinical management of breast cancer. Radiology 266:388–405CrossRef Groheux D, Espie M, Giacchetti S, Hindie E (2013) Performance of FDG PET/CT in the clinical management of breast cancer. Radiology 266:388–405CrossRef
3.
go back to reference Kajáry K, Tőkés T, Dank M, Kulka J, Szakáll S Jr, Lengyel Z (2015) Correlation of the value of 18F-FDG uptake, described by SUVmax, SUVavg, metabolic tumour volume and total lesion glycolysis, to clinicopathological prognostic factors and biological subtypes in breast cancer. Nucl Med Comm 36:28–37CrossRef Kajáry K, Tőkés T, Dank M, Kulka J, Szakáll S Jr, Lengyel Z (2015) Correlation of the value of 18F-FDG uptake, described by SUVmax, SUVavg, metabolic tumour volume and total lesion glycolysis, to clinicopathological prognostic factors and biological subtypes in breast cancer. Nucl Med Comm 36:28–37CrossRef
5.
go back to reference Morris ED, Endres CJ, Schmidt KC, Christian BT, Muic RJ, Fisher RE (2004) Kinetic modeling in positron emission tomography. In: Wernick MN, Aarsvold JN (eds) Emission tomography. The fundamentals of PET and SPECT. Elsevier Academic Press, San Diego, pp 499–540CrossRef Morris ED, Endres CJ, Schmidt KC, Christian BT, Muic RJ, Fisher RE (2004) Kinetic modeling in positron emission tomography. In: Wernick MN, Aarsvold JN (eds) Emission tomography. The fundamentals of PET and SPECT. Elsevier Academic Press, San Diego, pp 499–540CrossRef
6.
go back to reference Kelloff GJ, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY et al (2005) Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 11:2785–2808CrossRef Kelloff GJ, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY et al (2005) Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 11:2785–2808CrossRef
7.
go back to reference Curigliano G, Burstein HJ, Winer EP, Gnant M, Dubsky P, Loibl S et al (2017) De-escalating and escalating treatments for early-stage breast cancer: the St Gallen international expert consensus conference on the primary therapy of early breast Cancer 2017. Ann Oncol 28:1700–1712CrossRef Curigliano G, Burstein HJ, Winer EP, Gnant M, Dubsky P, Loibl S et al (2017) De-escalating and escalating treatments for early-stage breast cancer: the St Gallen international expert consensus conference on the primary therapy of early breast Cancer 2017. Ann Oncol 28:1700–1712CrossRef
8.
go back to reference Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G et al (2015) The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILsWorking Group 2014. Ann Oncol 26:259–271CrossRef Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G et al (2015) The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILsWorking Group 2014. Ann Oncol 26:259–271CrossRef
10.
go back to reference Soret M, Bacharach SL, Buvat I (2007) Partial-volume effect in PET tumor imaging. J Nucl Med 48:932–945CrossRef Soret M, Bacharach SL, Buvat I (2007) Partial-volume effect in PET tumor imaging. J Nucl Med 48:932–945CrossRef
11.
go back to reference Brierley JD, Gospodarowicz MK, Wittekind C, editors in chief (2017) TNM classification of malignant tumours. Eighth Edition. Oxford: Wiley Brierley JD, Gospodarowicz MK, Wittekind C, editors in chief (2017) TNM classification of malignant tumours. Eighth Edition. Oxford: Wiley
12.
go back to reference Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168 Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168
13.
go back to reference Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ et al (2007) 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 25:118–145CrossRef Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ et al (2007) 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 25:118–145CrossRef
14.
go back to reference Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31:3997–4013CrossRef Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31:3997–4013CrossRef
15.
go back to reference Dowsett M, Nielsen TO, A'Hern R, Bartlett J, Coombes RC, Cuzick J et al (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103:1656–1664CrossRef Dowsett M, Nielsen TO, A'Hern R, Bartlett J, Coombes RC, Cuzick J et al (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103:1656–1664CrossRef
16.
go back to reference Pathmanathan N, Balleine RL (2013) Ki67 and proliferation in breast cancer. J Clin Pathol 66:512–516CrossRef Pathmanathan N, Balleine RL (2013) Ki67 and proliferation in breast cancer. J Clin Pathol 66:512–516CrossRef
17.
go back to reference Tokes AM, Szasz AM, Geszti F, Lukacs LV, Kenessey I, Turanyi E et al (2015) Expression of proliferation markers Ki67, cyclin A, geminin and aurora-kinase A in primary breast carcinomas and corresponding distant metastases. J Clin Pathol 68:274–282CrossRef Tokes AM, Szasz AM, Geszti F, Lukacs LV, Kenessey I, Turanyi E et al (2015) Expression of proliferation markers Ki67, cyclin A, geminin and aurora-kinase A in primary breast carcinomas and corresponding distant metastases. J Clin Pathol 68:274–282CrossRef
18.
go back to reference Shankar LK, Hoffman JM, Bacharach S, Graham MM, Karp J, Lammertsma AA et al (2006) Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. J Nucl Med 47:1059–1066PubMed Shankar LK, Hoffman JM, Bacharach S, Graham MM, Karp J, Lammertsma AA et al (2006) Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. J Nucl Med 47:1059–1066PubMed
19.
go back to reference Boellaard R, O'Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG et al (2010) FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging 37:181–200CrossRef Boellaard R, O'Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG et al (2010) FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging 37:181–200CrossRef
20.
go back to reference Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Charlop A, Lawton TJ et al (2002) Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy. J Nucl Med 43:500–509PubMed Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Charlop A, Lawton TJ et al (2002) Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy. J Nucl Med 43:500–509PubMed
21.
go back to reference Dunnwald LK, Doot RK, Specht JM, Gralow JR, Ellis GK, Livingston RB et al (2011) PET tumor metabolism in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy: value of static versus kinetic measures of fluorodeoxyglucose uptake. Clin Cancer Res 17:2400–2409CrossRef Dunnwald LK, Doot RK, Specht JM, Gralow JR, Ellis GK, Livingston RB et al (2011) PET tumor metabolism in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy: value of static versus kinetic measures of fluorodeoxyglucose uptake. Clin Cancer Res 17:2400–2409CrossRef
22.
go back to reference Doot RK, Dunnwald LK, Schubert EK, Muzi M, Peterson LM, Kinahan PE et al (2007) Dynamic and static approaches to quantifying 18F-FDG uptake for measuring cancer response to therapy, including the effect of granulocyte CSF. J Nucl Med 48:920–925CrossRef Doot RK, Dunnwald LK, Schubert EK, Muzi M, Peterson LM, Kinahan PE et al (2007) Dynamic and static approaches to quantifying 18F-FDG uptake for measuring cancer response to therapy, including the effect of granulocyte CSF. J Nucl Med 48:920–925CrossRef
23.
go back to reference Partridge SC, Vanantwerp RK, Doot RK, Chai X, Kurland BF, Eby PR et al (2010) Association between serial dynamic contrast-enhanced MRI and dynamic 18F-FDG PET measures in patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer. J Magn Reson Imaging 32:1124–1131CrossRef Partridge SC, Vanantwerp RK, Doot RK, Chai X, Kurland BF, Eby PR et al (2010) Association between serial dynamic contrast-enhanced MRI and dynamic 18F-FDG PET measures in patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer. J Magn Reson Imaging 32:1124–1131CrossRef
24.
go back to reference Tseng J, Dunnwald LK, Schubert EK, Link JM, Minoshima S, Muzi M et al (2004) 18F-FDG kinetics in locally advanced breast cancer: correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. J Nucl Med 45:1829–1837PubMed Tseng J, Dunnwald LK, Schubert EK, Link JM, Minoshima S, Muzi M et al (2004) 18F-FDG kinetics in locally advanced breast cancer: correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. J Nucl Med 45:1829–1837PubMed
25.
go back to reference Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Specht JM et al (2008) 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 26:4449–4457CrossRef Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Specht JM et al (2008) 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 26:4449–4457CrossRef
26.
go back to reference Eby PR, Partridge SC, White SW, Doot RK, Dunnwald LK, Schubert EK et al (2008) Metabolic and vascular features of dynamic contrast-enhanced breast magnetic resonance imaging and (15)O-water positron emission tomography blood flow in breast cancer. Acad Radio 15:1246–1254CrossRef Eby PR, Partridge SC, White SW, Doot RK, Dunnwald LK, Schubert EK et al (2008) Metabolic and vascular features of dynamic contrast-enhanced breast magnetic resonance imaging and (15)O-water positron emission tomography blood flow in breast cancer. Acad Radio 15:1246–1254CrossRef
27.
go back to reference Wangerin KA, Muzi M, Peterson LM, Linden HM, Novakova A, Mankoff DA et al (2017) A virtual clinical trial comparing static versus dynamic PET imaging in measuring response to breast cancer therapy. Phys Med Biol 62:3639–3655CrossRef Wangerin KA, Muzi M, Peterson LM, Linden HM, Novakova A, Mankoff DA et al (2017) A virtual clinical trial comparing static versus dynamic PET imaging in measuring response to breast cancer therapy. Phys Med Biol 62:3639–3655CrossRef
28.
go back to reference Lee S, Choi S, Kim SY, Yun MJ, Kim HI (2017) Potential utility of FDG PET-CT as a non-invasive tool for monitoring local immune responses. J Gastric Cancer 17:384–393CrossRef Lee S, Choi S, Kim SY, Yun MJ, Kim HI (2017) Potential utility of FDG PET-CT as a non-invasive tool for monitoring local immune responses. J Gastric Cancer 17:384–393CrossRef
29.
go back to reference Lopci E, Toschi L, Grizzi F, Rahal D, Olivari L, Castino GF et al (2016) Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery. Eur J Nucl Med Mol Imaging 43:1954–1961CrossRef Lopci E, Toschi L, Grizzi F, Rahal D, Olivari L, Castino GF et al (2016) Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery. Eur J Nucl Med Mol Imaging 43:1954–1961CrossRef
30.
go back to reference Fujii T, Yanai K, Tokuda S, Nakazawa Y, Kurozumi S, Obayashi S et al (2018) Relationship between FDG uptake and neutrophil/lymphocyte ratio in patients with invasive ductal breast cancer. Anticancer Res 38:4927–4931CrossRef Fujii T, Yanai K, Tokuda S, Nakazawa Y, Kurozumi S, Obayashi S et al (2018) Relationship between FDG uptake and neutrophil/lymphocyte ratio in patients with invasive ductal breast cancer. Anticancer Res 38:4927–4931CrossRef
Metadata
Title
Dynamic FDG-PET/CT in the Initial Staging of Primary Breast Cancer: Clinicopathological Correlations
Authors
Kornélia Kajáry
Zsolt Lengyel
Anna-Mária Tőkés
Janina Kulka
Magdolna Dank
Tímea Tőkés
Publication date
01-04-2020
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 2/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-019-00641-0

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