AIM: This study examines the combination of FES-PET and FDG-PET as complementary imaging for detection of metastatic ILC. METHODS: We retrospectively evaluated FES and FDG uptake in patients with metastatic ILC from an estrogen receptor (ER) positive primary tumor. We classified lesions into three categories (FES high/FDG low, FES high/FDG high, FES low/FDG low) using SUVmax cut-off values of 1.5 for FES and 5.0 for FDG. Qualitative evaluation included examination of the difference in the extent of disease between FES and FDG. RESULTS: Of the 38 patients, 82% had FES uptake in all tumor sites identified by FDG, with 18% lacking FES uptake in at least one lesion. Mean (range) SUVmax for FES and FDG was 4.0 (0.67-10.6) and 4.6 (1.3-12.5), respectively. The majority of ILC patients (25/38), had lesions with FES high/FDG low uptake, consistent with the strongly ER + indolent nature of ILC. Patients with disease classified as FES high/FDG low had longer median overall survival (OS) (3.2 years) and progression-free survival (PFS) (1.5 years) than FES high/FDG high (OS = 2.1 years and PFS = 0.46 years). The median overall OS for all patients was 3.0 years (95% CI 2.5, 4.8) and PFS of 1.3 years (95% CI 0.6, 2.5). 8 patients (21%) had qualitatively more extensive disease by FES-PET. CONCLUSIONS: Our findings suggest that both FES-PET and FDG-PET can identify metastatic ILC and be useful in detecting the pattern and extent of disease. The imaging combination provides additional information for prognosis and clinical decision making, balancing suitability for endocrine therapy and aggressiveness/indolence of disease.

Charles University and Thomayer Hospital Prague Czech Republic

Fred Hutchinson Cancer Research Center FHCC 1144 Eastlake Seattle WA 98109 1023 USA

GSK Philadelphia PA USA

University of Pennsylvania Philadelphia PA USA

University of Washington Seattle WA USA

Zobrazit více v PubMed

Mariotto AB, Etzioni R, Hurlbert M, Penberthy L, Mayer M (2017) Estimation of the number of women living with metastatic breast cancer in the United States. Cancer Epidemiol Biomarkers Prev 26(6):809–815 PubMed PMC

Li CI, Anderson BO, Daling JR, Moe RE (2003) Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA 289(11):1421–1424 PubMed

Dossus L, Benusiglio PR (2015) Lobular breast cancer: incidence and genetic and non-genetic risk factors. Breast Cancer Res 17:37 PubMed PMC

García-Fernández A, Lain JM, Chabrera C, García Font M, Fraile M, Barco I, Torras M, Reñe A, González S, González C, Piqueras M (2015) Comparative long-term study of a large series of patients with invasive ductal carcinoma and invasive lobular carcinoma. Loco-regional recurrence, metastasis, and survival. Breast J 21(5):533–7 PubMed

Adachi Y, Ishiguro J, Kotani H, Hisada T, Ichikawa M, Gondo N, Yoshimura A, Kondo N, Hattori M, Sawaki M et al (2016) Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma. BMC Cancer 16:248 PubMed PMC

Mouabbi JA, Hassan A, Lim B, Hortobagyi GN, Tripathy D, Layman RM (2022) Invasive lobular carcinoma: an understudied emergent subtype of breast cancer. Breast Cancer Res Treat 193(2):253–264 PubMed

Bos R, van Der Hoeven JJ, van Der Wall E, van Der Groep P, van Diest PJ, Comans EF, Joshi U, Semenza GL, Hoekstra OS, Lammertsma AA et al (2002) Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 20(2):379–387 PubMed

Buck A, Schirrmeister H, Kühn T, Shen C, Kalker T, Kotzerke J, Dankerl A, Glatting G, Reske S, Mattfeldt T (2002) FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. Eur J Nucl Med Mol Imaging 29(10):1317–1323 PubMed

Hogan MP, Goldman DA, Dashevsky B, Riedl CC, Gönen M, Osborne JR, Jochelson M, Hudis C, Morrow M, Ulaner GA (2015) Comparison of 18F-FDG PET/CT for systemic staging of newly diagnosed invasive lobular carcinoma versus invasive ductal carcinoma. J Nucl Med 56(11):1674–1680 PubMed PMC

National comprehensive cancer network guidelines version i.2024.invasive breast cancer. http://www.nccn.org. Accessed 11 Nov 2024

Aurilio G, Disalvatore D, Pruneri G, Bagnardi V, Viale G, Curigliano G, Adamoli L, Munzone E, Sciandivasci A, De Vita F et al (2014) A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur J Cancer 50(2):277–289 PubMed

Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, Oldfield M, Dranitsaris G, Tomlinson G, Laupacis A et al (2012) Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol 30(6):587–592 PubMed PMC

Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892 PubMed PMC

McGranahan N, Swanton C (2017) Clonal Heterogeneity and tumor evolution: past, present, and the Future. Cell 168(4):613–628 PubMed

Giuliano M, Schifp R, Osborne CK, Trivedi MV (2011) Biological mechanisms and clinical implications of endocrine resistance in breast cancer. Breast 20(Suppl 3):S42-49 PubMed

Sighoko D, Liu J, Hou N, Gustafson P, Huo D (2014) Discordance in hormone receptor status among primary, metastatic, and second primary breast cancers: biological difference or misclassification? Oncologist 19(6):592–601 PubMed PMC

Ulaner GA, Vaz SC (2024) Women’s health update: growing role of pet for patients with breast cancer. Semin Nucl Med 54(2):247–255 PubMed

Kurland BF, Wiggins JR, Coche A, Fontan C, Bouvet Y, Webner P, Divgi C, Linden HM (2020) Whole-body characterization of estrogen receptor status in metastatic breast cancer with 16α-18f-fluoro-17β-estradiol positron emission tomography: meta-analysis and recommendations for integration into clinical applications. Oncologist 25(10):835–844 PubMed PMC

Peterson LM, Kurland BF, Yan F, Jiresova AN, Gadi VK, Specht JM, Gralow JR, Schubert EK, Link JM, Krohn KA et al (2021) F-fluoroestradiol PET imaging in a Phase II trial of vorinostat to restore endocrine sensitivity in ER+/HER2- metastatic breast cancer. J Nucl Med 62(2):184–190 PubMed PMC

Lindström LS, Yau C, Czene K, Thompson CK, Hoadley KA, Van’t Veer LJ, Balassanian R, Bishop JW, Carpenter PM, Chen YY et al (2018) Intratumor heterogeneity of the estrogen receptor and the long-term risk of fatal breast cancer. J Natl Cancer Inst 110(7):726–733 PubMed PMC

Almendro V, Kim HJ, Cheng YK, Gönen M, Itzkovitz S, Argani P, van Oudenaarden A, Sukumar S, Michor F, Polyak K (2014) Genetic and phenotypic diversity in breast tumor metastases. Cancer Res 74(5):1338–1348 PubMed PMC

Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ (2001) Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 19(11):2797–2803 PubMed

Linden HM, Stekhova SA, Link JM, Gralow JR, Livingston RB, Ellis GK, Petra PH, Peterson LM, Schubert EK, Dunnwald LK et al (2006) Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J Clin Oncol 24(18):2793–2799 PubMed

Dehdashti F, Mortimer JE, Trinkaus K, Naughton MJ, Ellis M, Katzenellenbogen JA, Welch MJ, Siegel BA (2009) PET-based estradiol challenge as a predictive biomarker of response to endocrine therapy in women with estrogen-receptor-positive breast cancer. Breast Cancer Res Treat 113(3):509–517 PubMed PMC

Peterson LM, Kurland BF, Schubert EK, Link JM, Gadi VK, Specht JM, Eary JF, Porter P, Shankar LK, Mankoff DA et al (2014) A phase 2 study of 16α-[18F]-fluoro-17β-estradiol positron emission tomography (FES-PET) as a marker of hormone sensitivity in metastatic breast cancer (MBC). Mol Imaging Biol 16(3):431–440 PubMed PMC

Boers J, Venema CM, de Vries EFJ, Glaudemans AWJM, Kwee TC, Schuuring E, Martens JWM, Elias SG, Hospers GAP, Schröder CP (2020) Molecular imaging to identify patients with metastatic breast cancer who benefit from endocrine treatment combined with cyclin-dependent kinase inhibition. Eur J Cancer 126:11–20 PubMed

Venema C, de Vries E, Glaudemans A, Poppema B, Hospers G, Schröder C (2017) 18F-FES PET has added value in staging and therapy decision making in patients with disseminated lobular breast cancer. Clin Nucl Med 42(8):612–614 PubMed

Ulaner GA, Jhaveri K, Chandarlapaty S, Hatzoglou V, Riedl CC, Lewis JS, Mauguen A (2021) Head-to-head evaluation of 18F-FES and 18F-FDG PET/CT in metastatic invasive lobular breast cancer. J Nucl Med 62(3):326–331 PubMed PMC

Liu C, Ma G, Xu X, Song S, Yang Z (2024) Can 18F-FES PET Improve the Evaluation of 18F-FDG PET in patients with metastatic invasive lobular carcinoma? Clin Nucl Med 49(4):301–307 PubMed

Covington MF, Hoffman JM, Morton KA, Buckway B, Boucher KM, Rosenthal RE, Porretta JM, Brownson KE, Matsen CB, Vaklavas C et al (2023) Prospective Pilot Study of (18)F-Fluoroestradiol PET/CT in patients with invasive lobular carcinomas. AJR Am J Roentgenol 221(2):228–239 PubMed

Byrd DW, Doot RK, Allberg KC, MacDonald LR, McDougald WA, Elston BF, Linden HM, Kinahan PE (2016) Evaluation of cross-calibrated (68)Ge/(68)Ga phantoms for assessing PET/CT measurement bias in oncology imaging for single- and multicenter trials. Tomography 2(4):353–360 PubMed PMC

Kurland BF, Peterson LM, Shields AT, Lee JH, Byrd DW, Novakova-Jiresova A, Muzi M, Specht JM, Mankoff DA, Linden HM et al (2019) Test-retest reproducibility of (18)F-FDG PET/CT uptake in cancer patients within a qualified and calibrated local network. J Nucl Med 60(5):608–614 PubMed PMC

Tewson TJ, Mankoff DA, Peterson LM, Woo I, Petra P (1999) Interactions of 16alpha-[18F]-fluoroestradiol (FES) with sex steroid binding protein (SBP). Nucl Med Biol 26(8):905–913 PubMed

Ulaner GA, Mankoff DA, Clark AS, Fowler AM, Linden HM, Peterson LM, Dehdashti F, Kurland BF, Mortimer J, Mouabbi J et al (2023) Summary: appropriate use criteria for estrogen receptor-targeted PET imaging with 16alpha-(18)f-fluoro-17beta-fluoroestradiol. J Nucl Med 64(3):351–354 PubMed

Peterson LM, Kurland BF, Link JM, Schubert EK, Stekhova S, Linden HM, Mankoff DA (2011) Factors influencing the uptake of 18F-fluoroestradiol in patients with estrogen receptor positive breast cancer. Nucl Med Biol 38(7):969–978 PubMed PMC

Kurland BF, Peterson LM, Lee JH, Schubert EK, Currin ER, Link JM, Krohn KA, Mankoff DA, Linden HM (2017) Estrogen receptor binding (18F-FES PET) and Glycolytic Activity (18F-FDG PET) predict progression-free survival on endocrine therapy in patients with ER+ breast cancer. Clin Cancer Res 23(2):407–415 PubMed PMC

de Mooij CM, Mitea C, Mottaghy FM, Smidt ML, van Nijnatten TJA (2021) Value of (18)F-FDG PET/CT for predicting axillary pathologic complete response following neoadjuvant systemic therapy in breast cancer patients: emphasis on breast cancer subtype. EJNMMI Res 11(1):116 PubMed PMC

Han S, Lee SB, Gong G, Lee J, Chae SY, Oh JS, Moon DH (2023) Prognostic significance of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with T2N1 hormone receptor-positive, ERBB2-negative breast cancer who underwent adjuvant chemotherapy. Breast Cancer Res Treat 198(2):207–15 PubMed

Kurland BF, Oesterreich S (2018) Heterogeneity in metastatic breast cancer. J Nucl Med 59(8):1210–1211 PubMed PMC

Pestalozzi BC, Zahrieh D, Mallon E, Gusterson BA, Price KN, Gelber RD, Holmberg SB, Lindtner J, Snyder R, Thürlimann B et al (2008) Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 international breast cancer study group clinical trials. J Clin Oncol 26(18):3006–3014 PubMed

Di Meglio A, Freedman RA, Lin NU, Barry WT, Metzger-Filho O, Keating NL, King TA, Sertoli MR, Boccardo F, Winer EP et al (2016) Time trends in incidence rates and survival of newly diagnosed stage IV breast cancer by tumor histology: a population-based analysis. Breast Cancer Res Treat 157(3):587–596 PubMed

Zhang J, Jia Z, Ragaz J, Zhang YJ, Zhou M, Zhang YP, Li G, Wang BY, Wang ZH, Hu XC (2013) The maximum standardized uptake value of 18 F-FDG PET scan to determine prognosis of hormone-receptor positive metastatic breast cancer. BMC Cancer 13:42 PubMed PMC

Taghipour M, Wray R, Sheikhbahaei S, Wright JL, Subramaniam RM (2016) FDG avidity and tumor burden: survival outcomes for patients with recurrent breast cancer. AJR Am J Roentgenol 206(4):846–855 PubMed

Cachin F, Prince HM, Hogg A, Ware RE, Hicks RJ (2006) Powerful prognostic stratification by [18F]fluorodeoxyglucose positron emission tomography in patients with metastatic breast cancer treated with high-dose chemotherapy. J Clin Oncol 24(19):3026–3031 PubMed