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Measuring Response to Chemotherapy in Locally Advanced Breast Cancer: Methodological Considerations

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Breast Cancer

Abstract

In this chapter the findings of response-monitoring studies in breast cancer, using [18F]2-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET), are summarised. These studies indicate that there is a strong relationship between response and decrease in FDG signal even at an early stage of therapy. The review concentrates on methodological aspects of monitoring response with FDG: timing of serial scans, ROI definition approach, method of quantification, pitfalls of FDG and future directions in functional imaging. For the sake of optimal clinical applicability there now is need to standardise methodology. This is necessary to establish firm cut-off values for discriminating responders from non-responders, which in turn will provide a means for optimal treatment for as many patients as possible.

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References

  • Aboagye EO, Price PM (2003) Use of positron emission tomography in anticancer drug development. Invest New Drugs 21:169–181

    Article  PubMed  CAS  Google Scholar 

  • Avril N, Rose CA, Schelling M et al (2000) Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol 18:3495–3502

    PubMed  CAS  Google Scholar 

  • Bading JR, Alauddin MM, Fissekis JD et al (2000) Blocking catabolism with eniluracil enhances PET studies of 5-[18F]fluorouracil pharmacokinetics J Nucl Med 2000 41:1714–1724

    PubMed  CAS  Google Scholar 

  • Bassa P, Kim EE, Inoue T et al (1996) Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. J Nucl Med 37:931–938

    PubMed  CAS  Google Scholar 

  • Beenken SW, Urist MM, Zhang Y et al (2003) Axillary lymph node status, but not tumor size, predicts locoregional recurrence and overall survival after mastectomy for breast cancer. Ann Surg 237:732–739

    Article  PubMed  Google Scholar 

  • Boellaard R, Krak NC, Hoekstra OS et al (2004) Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med 45:1519–1527

    PubMed  Google Scholar 

  • Botker HE, Bottcher M, Schmitz O et al (1997) Glucose uptake and lumped constant variability in normal human hearts determined with [18F]fluorodeoxyglucose. J Nucl Cardiol 4:125–132

    Article  PubMed  CAS  Google Scholar 

  • Bos R, van Der Hoeven JJ, van Der Wall E et al (2002) Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 20:379–387

    Article  PubMed  CAS  Google Scholar 

  • Breslin TM, Cohen L, Sahin A et al (2000) Sentinel lymph node biopsy is accurate after neoadjuvant chemotherapy for breast cancer. J Clin Oncol 18:3480–3486

    PubMed  CAS  Google Scholar 

  • Bruce DM, Evans NT, Heys SD et al (1995) Positron emission tomography: 2-deoxy-2-[18F]-fluoro-D-glucose uptake in locally advanced breast cancers. Eur J Surg Oncol 21:280–283

    Article  PubMed  CAS  Google Scholar 

  • Buchmann I, Vogg AT, Glatting G et al (2003) [18F]5-fluoro-2-deoxyuridine-PET for imaging of malignant tumors and for measuring tissue proliferation. Cancer Biother Radiopharm 18:327–337

    Article  PubMed  CAS  Google Scholar 

  • Burcombe RJ, Makris A, Pittam M et al (2002) Evaluation of good clinical response to neoadjuvant chemotherapy in primary breast cancer using [18F]-fluorodeoxyglucose positron emission tomography. Eur J Cancer 38:375–379

    Article  PubMed  CAS  Google Scholar 

  • Cheung YC, Chen SC, Su MY et al (2003) Monitoring the size and response of locally advanced breast cancers to neoadjuvant chemotherapy (weekly paclitaxel and epirubicin) with serial enhanced MRI. Breast Cancer Res Treat 78:51–58

    Article  PubMed  CAS  Google Scholar 

  • Crippa F, Gerali A, Alessi A et al (2004) FDG-PET for axillary lymph node staging in primary breast cancer. Eur J Nucl Med Mol Imaging 31:S97–S102

    Article  PubMed  Google Scholar 

  • Delille JP, Slanetz PJ, Yeh ED et al (2003) Invasive ductal breast carcinoma response to neoadjuvant chemotherapy: noninvasive monitoring with functional MR imaging pilot study. Radiology 228:63–69

    Article  PubMed  Google Scholar 

  • Dixon JM, Jackson J, Renshaw L et al (2003) Neoadjuvant tamoxifen and aromatase inhibitors: comparisons and clinical outcomes. J Steroid Biochem Mol Biol 86:295–299

    Article  PubMed  CAS  Google Scholar 

  • Eltahir A, Heys SD, Hutcheon AW et al (1998) Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy. Am J Surg 175:127–132

    Article  PubMed  CAS  Google Scholar 

  • Erselcan T, Turgut B, Dogan D et al (2002) Lean body massbased standardized uptake value, derived from a predictive equation, might be misleading in PET studies. Eur J Nucl Med Mol Imaging 29:1630–1638

    Article  PubMed  Google Scholar 

  • Fisher B, Bryant J, Wolmark N et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685

    PubMed  CAS  Google Scholar 

  • Formenti SC, Volm M, Skinner KA et al (2003) Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicinbased chemotherapy in locally advanced breast cancer: a phase I/II trial. J Clin Oncol 21:864–870

    Article  PubMed  CAS  Google Scholar 

  • Freedman NM, Sundaram SK, Kurdziel K et al (2003) Comparison of SUV and Patlak slope for monitoring of cancer therapy using serial PET scans. Eur J Nucl Med Mol Imaging 30:46–53

    Article  PubMed  Google Scholar 

  • Gajdos C, Tartter PI, Estabrook A et al (2002) Relationship of clinical and pathologic response to neoadjuvant chemotherapy and outcome of locally advanced breast cancer. J Surg Oncol 80:4–11

    Article  PubMed  Google Scholar 

  • de Geus-Oei LF, Visser EP, Krabbe PF et al (2006) Comparison of image-derived and arterial input functions for estimating the rate of glucose metabolism in therapy-monitoring 18F-FDG PET studies. J Nucl Med 47:945–949

    PubMed  Google Scholar 

  • Graham MM, Peterson LM, Hayward RM (2000) Comparison of simplified quantitative analysis of FDG uptake. Nucl Med Biology 27:647–655

    Article  CAS  Google Scholar 

  • Graham MM, Muzi M, Spence AM et al (2002) The FDG lumped constant in normal human brain. J Nucl Med 43:1157–1166

    PubMed  Google Scholar 

  • Greijer AE, de Jong MC, Scheffer GL et al (2005) Hypoxiainduced acidification causes mitoxantrone resistance not mediated by drug transporters in human breast cancer cells. Cell Oncol 27:43–49

    PubMed  CAS  Google Scholar 

  • Herrada J, Iyer RB, Atkinson EN et al (1997) Relative value of physical examination, mammography, and breast sonography in evaluating the size of the primary tumor and regional lymph node metastases in women receiving neoadjuvant chemotherapy for locally advanced breast carcinoma. Clin Cancer Res 3:1565–1569

    PubMed  CAS  Google Scholar 

  • Helvie MA, Joynt LK, Cody RL et al (1996) Locally advanced breast carcinoma: accuracy of mammography versus clinical examination in the prediction of residual disease after chemotherapy. Radiology 198:327–332

    PubMed  CAS  Google Scholar 

  • Hendrikse NH, de Vries EG, Eriks-Fluks L et al (1999) A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier. Cancer Res 59:2411–2416

    PubMed  CAS  Google Scholar 

  • Herholz K, Pietrzyk U, Voges J et al (1993) Correlation of glucose consumption and tumor cell density in astrocytomas. A stereotactic PET study. J Neurosurg 79:853–858

    Article  PubMed  CAS  Google Scholar 

  • Higashi K, Clavo AC, Wahl RL (1993) Does FDG uptake measure proliferative activity of human cancer cells? In vitro comparison with DNA flow cytometry and tritiated thymidine uptake. J Nucl Med 34:414–419

    PubMed  CAS  Google Scholar 

  • Hoekstra CJ, Paglianiti I, Hoekstra OS et al (2000) Monitoring response to therapy in cancer using [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography: an overview of different analytical methods. Eur J Nucl Med 27:731–743

    Article  PubMed  CAS  Google Scholar 

  • Hoekstra CJ, Hoekstra OS, Stroobants SG et al (2002) Methods to monitor response to chemotherapy in non-small cell lung cancer with 18F-FDG PET. J Nucl Med 43:1304–1309

    PubMed  CAS  Google Scholar 

  • Honkoop AH, Pinedo HM, De Jong JS et al (1997) Effects of chemotherapy on pathologic and biologic characteristics of locally advanced breast cancer. Am J Clin Pathol 107:211–218

    PubMed  CAS  Google Scholar 

  • Honkoop AH, van Diest PJ, de Jong JS et al (1998) Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer. Br J Cancer 77:621–626

    PubMed  CAS  Google Scholar 

  • Huang SC (2000) Anatomy of SUV. Nucl Med Biol 27:643–646

    Article  PubMed  CAS  Google Scholar 

  • Huang SC, Phelps ME, Hoffman EJ et al (1980) Noninvasive determination of local cerebral metabolic rate of glucose in man. Am J Physiol 238:E69–E82

    PubMed  CAS  Google Scholar 

  • Hunter GJ, Hamberg LM, Alpert NM et al (1996) Simplified measurement of deoxyglucose utilization rate. J Nucl Med 37:950–955

    PubMed  CAS  Google Scholar 

  • Hutcheon AW, Heys SD, Sarkar TK (2003) Neoadjuvant docetaxel in locally advanced breast cancer. Breast Cancer Res Treat 79:S19–S24

    Article  PubMed  CAS  Google Scholar 

  • Jansson T, Westlin JE, Ahlstrom H et al (1995) Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation? J Clin Oncol 13:1470–1477

    PubMed  CAS  Google Scholar 

  • Keen HG, Dekker BA, Disley L et al (2005) Imaging apoptosis in vivo using 124I-annexin V and PET. Nucl Med Biol 32:395–402

    Article  PubMed  CAS  Google Scholar 

  • Keyes JW Jr (1995) SUV: standard uptake or silly useless value? J Nucl Med 36:1836–1839

    PubMed  Google Scholar 

  • Kim SJ, Kim SK, Lee ES et al (2004) Predictive value of [18F]FDG PET for pathological response of breast cancer to neo-adjuvant chemotherapy. Ann Oncol 15:1352–1357

    Article  PubMed  Google Scholar 

  • Krak NC, Boellaard R, Hoekstra OS et al (2005) Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging 32:294–301

    Article  PubMed  Google Scholar 

  • Krak NC, van der Hoeven JJ, Hoekstra OS et al (2003) Measuring [18F]FDG uptake in breast cancer during chemotherapy: comparison of analytical methods. Eur J Nucl Med Mol Imaging 30:674–681

    Article  PubMed  CAS  Google Scholar 

  • Kroep JR, Van Groeningen CJ, Cuesta MA (2003) Positron emission tomography using 2-deoxy-2-[18F]-fluoro-Dglucose for response monitoring in locally advanced gastroesophageal cancer; a comparison of different analytical methods. Mol Imaging Biol 5:337–346

    Article  PubMed  Google Scholar 

  • Kuerer HM, Newman LA, Buzdar AU et al (1998) Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer. Am J Surg 176:502–509

    Article  PubMed  CAS  Google Scholar 

  • Kurebayashi J (2005) Resistance to endocrine therapy in breast cancer. Cancer Chemother Pharmacol 56:S39–S46

    Article  CAS  Google Scholar 

  • Lammertsma AA, Hoekstra CJ, Giaconne G et al (2006) How should we analyse FDG PET studies for monitoring tumour response? Eur J Nucl Med Mol Imaging 33(Suppl 1):16–21

    Article  PubMed  Google Scholar 

  • Lind P, Igerc I, Beyer T et al (2004) Advantages and limitations of FDG PET in the follow-up of breast cancer. Eur J Nucl Med Mol Imaging 31:S125–S134

    Article  PubMed  Google Scholar 

  • Machiavelli MR, Romero AO, Perez JE et al (1998) 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 4:125–131

    PubMed  CAS  Google Scholar 

  • Mankoff DA, Dunnwald LK, Gralow JR et al (2002) Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy. J Nucl Med 43:500–509

    PubMed  Google Scholar 

  • Mankoff DA, Dunnwald LK, Gralow JR et al (2003) Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy. J Nucl Med 44:1806–1814

    PubMed  Google Scholar 

  • McIntosh SA, Ogston KN, Payne S et al (2003) Local recurrence in patients with large and locally advanced breast cancer treated with primary chemotherapy. Am J Surg 185:525–531

    Article  PubMed  Google Scholar 

  • Moll UM, Chumas J (1997) Morphologic effects of neoadjuvant chemotherapy in locally advanced breast cancer. Pathol Res Pract 193:187–196

    PubMed  CAS  Google Scholar 

  • Moneer M, Ismael S, Khaled H et al (2001) A new surgical strategy for breast conservation in locally advanced breast cancer that achieves a good locoregional control rate: preliminary report. Breast 10:220–224

    Article  PubMed  CAS  Google Scholar 

  • Mortimer JE, Dehdashti F, Siegel BA et al (2001) Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 19:2797–2803

    PubMed  CAS  Google Scholar 

  • Newman LA, Pernick NL, Adsay V et al (2003) Histopathologic evidence of tumor regression in the axillary lymph nodes of patients treated with preoperative chemotherapy correlates with breast cancer outcome. Ann Surg Oncol 10:734–739

    Article  PubMed  Google Scholar 

  • Oshida M et al, Uno K, Suzuki M et al (1998) Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose. Cancer 82:2227–2234

    Article  PubMed  CAS  Google Scholar 

  • Patlak CS, Blasberg RG, Fenstermacher JD (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1–7

    PubMed  CAS  Google Scholar 

  • Phelps ME, Huang SC, Hoffman EJ et al (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 6:371–388

    Article  PubMed  CAS  Google Scholar 

  • Pinedo HM, de Gruijl TD, van Der Wall E et al (2000) Biological concepts of prolonged neoadjuvant treatment plus GM-CSF in locally advanced tumors. Oncologist 5:497–500

    Article  PubMed  CAS  Google Scholar 

  • Pio BS, Park CK, Pietras R et al (2006) Usefulness of 3’-[F-18]fluoro-3’-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol Imaging Biol 8:36–42

    Article  PubMed  Google Scholar 

  • Pupa SM, Bufalino R, Invernizzi AM et al (1996) Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas. J Clin Oncol 14:85–94

    PubMed  CAS  Google Scholar 

  • Rajendran JG, Mankoff DA, O’Sullivan F et al (2004) Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res 10:2245–2252

    Article  PubMed  CAS  Google Scholar 

  • Reivich M, Kuhl D, Wolf A, Greenberg J et al (1979) The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 44:127–137

    PubMed  CAS  Google Scholar 

  • Rischin D, Hicks RJ, Fisher R et al (2006) Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02. J Clin Oncol 24:2098–2104

    Article  PubMed  Google Scholar 

  • Rosen EL, Blackwell KL, Baker JA et al (2003) Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. AJR Am J Roentgenol 181:1275–1282

    PubMed  Google Scholar 

  • Sadato N, Tsuchida T, Nakaumra S et al (1998) Non-invasive estimation of the net influx constant using the standardized uptake value for quantification of FDG uptake of tumours. Eur J Nucl Med 25:559–564

    Article  PubMed  CAS  Google Scholar 

  • Schelling M, Avril N, Nahrig J et al (2000) Positron emission tomography using [18F]fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 18:1689–1695

    PubMed  CAS  Google Scholar 

  • Selberg O, Muller MJ, van den Hoff J et al (2002) Use of positron emission tomography for the assessment of skeletal muscle glucose metabolism. Nutrition 18:323–328

    Article  PubMed  CAS  Google Scholar 

  • Shankar LK, Hoffman JM, Bacharach S 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 47:1059–1066

    PubMed  CAS  Google Scholar 

  • Smith IC, Welch AE, Hutcheon AW et al (2000) Positron emission tomography using [18F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol 18:1676–1688

    PubMed  CAS  Google Scholar 

  • Smith-Jones PM, Solit D, Afroze F et al (2006) Early tumor response to Hsp90 therapy using HER2 PET: comparison with 18F-FDG PET. J Nucl Med 47:793–796

    PubMed  CAS  Google Scholar 

  • Sokoloff L, Reivich M, Kennedy C et al (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916

    Article  PubMed  CAS  Google Scholar 

  • Spaepen K, Stroobants S, Dupont P et al (2003) [18F]FDG PET monitoring of tumour response to chemotherapy: does [(18)F]FDG uptake correlate with the viable tumour cell fraction? Eur J Nucl Med Mol Imaging 30:682–688

    Article  PubMed  CAS  Google Scholar 

  • Spence AM, Muzi M, Graham MM et al (1998) Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant. J Nucl Med 39:440–448

    PubMed  CAS  Google Scholar 

  • Steele RJ, Brown M, Eremin O (1985) Characterisation of macrophages infiltrating human mammary carcinomas. Br J Cancer 51:135–138

    PubMed  CAS  Google Scholar 

  • Teicher BA (1994) Hypoxia and drug resistance. Cancer Metastasis Rev 13:139–168

    Article  PubMed  CAS  Google Scholar 

  • van Tilburg EW, Franssen EJF, van der Hoeven JJM et al (2004) Radiosynthesis of [11C]-docetaxel. J Label Compd Radiopharm 47:763–777

    Article  CAS  Google Scholar 

  • Tiling R, Linke R, Untch M et al (2001) 18F-FDG PET and 99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study. Eur J Nucl Med 28:711–720

    Article  PubMed  CAS  Google Scholar 

  • Van der Weerdt AP, Klein LJ, Boellaard R et al (2001) Imagederived input functions for determination of MRglu in cardiac 18F-FDG PET scans. J Nucl Med 42:1622–1629

    PubMed  Google Scholar 

  • Virtanen KA, Peltoniemi P, Marjamaki P et al (2001) Human adipose tissue glucose uptake determined using [18F]-fluoro-deoxy-glucose ([18F]FDG) and PET in combination with microdialysis. Diabetologia 44:2171–2179

    Article  PubMed  CAS  Google Scholar 

  • Wahl RL, Zasadny K, Helvie M et al (1993) Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 11:2101–2111

    PubMed  CAS  Google Scholar 

  • Wahl RL, Siegel BA, Coleman RE et al (2004) Prospective multicenter study of axillary nodal staging by positron emission tomography in breast cancer: a report of the staging breast cancer with PET Study Group. J Clin Oncol 22:277–285

    Article  PubMed  Google Scholar 

  • Wu HM, Huang SC, Choi Y et al (1995) A modeling method to improve quantitation of fluorodeoxyglucose uptake in heterogeneous tumor tissue. J Nucl Med 36:297–306

    PubMed  CAS  Google Scholar 

  • Wu HM, Hoh CK, Huang SC et al (1996) Quantification of serial tumor glucose metabolism. J Nucl Med 37:506–513

    PubMed  CAS  Google Scholar 

  • Wu HM, Bergsneider M, Glenn TC et al (2003) Measurement of the global lumped constant for 2-deoxy-2-[18F]fluoro-D-glucose in normal human brain using [15O]water and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography imaging. A method with validation based on multiple methodologies. Mol Imaging Biol 5:32–41

    Article  PubMed  Google Scholar 

  • Young H, Baum R, Cremerius U et al (1999) Measurement of clinical and subclinical tumour response using [18F]-fluoredeoxyglucose and positron emisson tomography: review and 1999 EORTC recommendations. Eur J Cancer 35:1773–1782

    Article  PubMed  CAS  Google Scholar 

  • Zasadny KR, Wahl RL (1996) Enhanced FDG-PET tumor imaging with correlation-coefficient filtered influx-constant images. J Nucl Med 37:371–374

    PubMed  CAS  Google Scholar 

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Krak, N.C., Hoekstra, O.S., Lammertsma, A.A. (2008). Measuring Response to Chemotherapy in Locally Advanced Breast Cancer: Methodological Considerations. In: Bombardieri, E., Gianni, L., Bonadonna, G. (eds) Breast Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-36781-9_13

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