Association of Standardized Uptake Values of Primary Breast Cancer on [18F]FDG PET/CT With Immunohistochemistry and Molecular Subtypes Correlation of SUV of primary BC with molecular subtypes

Nishita Goyal (1), Periakaruppan Gokulakrishnan (2), Arunan Murali (3), Leena Joseph Dennis (4), Rajeswaran Rangasami (5), Bhawna Dev (6)
(1) Department of Radio-diagnosis, Sri Ramachandra Institute Of Higher Education & Research, Porur, Chennai, India, India,
(2) Department of radio-diagnosis, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai. India, India,
(3) Department of Radio diagnosis Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India, India,
(4) Department of Pathology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India., India,
(5) Deprtment of Radio-diagnosis Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India., India,
(6) Department of Radio-diagnosis, Sri Ramachandra Institute of Higher Education & Research, Porur Chennai, India., India

Abstract

Background: The prognostic factors for breast cancer include pretreatment staging, nodal and distant metastasis, hormone receptor status, ki67 index, and molecular subtype. For adequate treatment, [18F]FDG PET/CT is now being used to prognosticate the course and response of treatment in breast cancer patients. Our study aims to find the association between the metabolic activity of primary breast tumors as PET/CT SUV uptake and prognostic factors such as ER/PgR/Her2neu receptor status, molecular subtypes, ki67 labeling index, and nodal/distant metastasis.


Methods: A retrospective observational study at our tertiary care institute included 228 breast cancer patients from March 2017 to April 2021. Pretreatment PET/CT imaging was done. The immunohistochemical analysis was performed on a biopsy/surgical specimen to determine the molecular subtype of breast cancer. Further, statistical analysis was performed to find the association between PET/CT findings with immunohistochemistry and thus, molecular subtypes of breast cancers.


Results: Significantly higher SUV max was seen in tumors with ER-negative (Mean SUVmax-11.6; P-value=0.002), PgR negative (Mean SUVmax-11.1; p value-0.0005), triple-negative receptor status (Mean SUVmax-13.7; P-value=0.004) and high Ki67 index (P-value=<0.01). Further Luminal A (Mean SUV max:6.0±5.5 & Median SUV max:3.9±3.6) and Luminal B (Mean SUV max: 8.9±4.9 & Median SUV max:7.6±4.0) subtypes showed lower SUV max as compared to Her2neu (Mean SUV max: 9.4±5.5 & Median SUV max:8.6±6.2) and TNBC (Mean SUV max: 13.7±12.4 & Median SUV max:10.0±7.6) subtypes. However, only a weak correlation was found for axillary nodal spread p-value – 0.02) and no significant correlation was seen for Her2 receptor status (Mean SUVmax-9.7; p value-0.178) and distant metastasis (P-value=0.26).


Conclusion: The values for different molecular subtypes can be used as Mean SUV or Median SUV uptake. However, owing to data skewing in practical scenarios, we suggest the use of median values with interquartile range for predicting the molecular subtypes of breast cancer on PET/CT imaging: Luminal A – Median SUV – 3.9 (IQR – 3.6); Luminal B ­­– Median SUV – 7.6 (IQR – 4.0); Her2neu Enriched – Median SUV 8.6 (IQR - 6.2); Triple-negative breast cancer - Median SUV 10.0 (IQR - 7.6).

Full text article

Generated from XML file

References

Brock CS, Meikle SR, Price P. Does fluorine-18 fluorodeoxyglucose metabolic imaging of tumors benefit oncology? Eur J Nucl Med. 1997 Jun;24(6):691–705. doi: 10.1007/BF00841411.

Oshida M, Uno K, Suzuki M, Nagashima T, Hashimoto H, Yagata H, et al. Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose. Cancer. 1998 Jun 1;82(11):2227–34. PMID: 9610703

Mauri FA, Maisonneuve P, Caffo O, Veronese S, Aldovini D, Ferrero S, et al. The prognostic value of estrogen receptor status can be improved by combined evaluation of p53, Bcl2, and PgR expression: an immunohistochemical study on breast carcinoma with long-term follow-up. Int J Oncol. 1999 Dec;15(6):1137–1184. doi: 10.3892/ijo.15.6.1137

Clahsen PC, van de Velde CJ, Duval C, Pallud C, Mandard AM, Delobelle-Deroide A, et al. The utility of mitotic index, estrogen receptor, and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol. 1999 Aug;25(4):356–63. doi: 10.1053/ejso.1999.0657.

Ekmekcioglu O, Aliyev A, Yilmaz S, Arslan E, Kaya R, Kocael P, et al. Correlation of 18F-fluorodeoxyglucose uptake with histopathological prognostic factors in breast carcinoma. Nucl Med Commun. 2013 Nov;34(11):1055–67. DOI: 10.1097/MNM.0b013e3283658369.

Kitajima K, Fukushima K, Miyoshi Y, Nishimura A, Hirota S, Igarashi Y, et al. Association between 18F-FDG uptake and molecular subtype of breast cancer. Eur J Nucl Med Mol Imaging. 2015 Aug;42(9):1371–7. doi: 10.1007/s00259-015-3070-1.

Koolen BB, Vrancken Peeters MJTFD, Wesseling J, Lips EH, Vogel WV, Aukema TS, et al. Association of primary tumor FDG uptake with clinical, histopathological, and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging. 2012 Dec;39(12):1830–8. doi: 10.1007/s00259-012-2211-z.

Ueda S, Tsuda H, Asakawa H, Shigekawa T, Fukatsu K, Kondo N, et al. Clinicopathological and prognostic relevance of uptake level using 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in primary breast cancer. Jpn J Clin Oncol. 2008 Apr;38(4):250–8. doi: 10.1093/jjco/hyn019.

Abubakar ZA, Akepati NKR, Bikkina P. Correlation of Maximum Standardized Uptake Values in 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography Scan with Immunohistochemistry and Other Prognostic Factors in Breast Cancer. Indian J Nucl Med. 2019 Jan-Mar;34(1):10–13. doi: 10.4103/ijnm.IJNM_94_18.

Groheux D, Giacchetti S, Moretti JL, Porcher R, Espié M, Lehmann-Che J, et al. Correlation of high 18F-FDG uptake to clinical, pathological, and biological prognostic factors in breast cancer. Eur J Nucl Med Mol Imaging. 2011 Mar;38(3):426–35. doi: 10.1007/s00259-010-1640-9.

Mavi A, Cermik TF, Urhan M, Puskulcu H, Basu S, Yu JQ, et al. The effects of estrogen, progesterone, and C-erbB-2 receptor states on 18F-FDG uptake of primary breast cancer lesions. J Nucl Med. DOI: 10.2967/jnumed.106.037440.

Osborne JR, Port E, Gonen M, Doane A, Yeung H, Gerald W, et al. 18F-FDG PET of locally invasive breast cancer and association of estrogen receptor status with standardized uptake value: microarray and immunohistochemical analysis. J Nucl Med. 2010 Apr;51(4):543–50. doi: 10.2967/jnumed.108.060459.

Keam B, Im SA, Koh Y, Han SW, Oh DY, Cho N, et al. Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy. BMC Cancer. 2011 Oct 20;11(1):452. doi: 10.1186/1471-2407-11-452.

Uğurluer G, Yavuz S, Çalıkuşu Z, Seyrek E, Kibar M, Serin M, et al. Correlation between 18F-FDG Positron-Emission Tomography 18F-FDG Uptake Levels at Diagnosis and Histopathologic and Immunohistochemical Factors in Patients with Breast Cancer. J Breast Health. 2016 Jul 1;12(3):112–8. doi: 10.5152/tjbh.2016.3031.

Dondi F, Albano D, Bellini P, Camoni L, Treglia G, Bertagna F. Relationship between Baseline [18F]FDG PET/CT Semiquantitative Parameters and BRCA Mutational Status and Their Prognostic Role in Patients with Invasive Ductal Breast Carcinoma. Tomogr Ann Arbor Mich. 2022 Oct 27;8(6):2662–75. doi: 10.3390/tomography8060222.

Buck A, Schirrmeister H, Kühn T, Shen C, Kalker T, Kotzerke J, et al. FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. Eur J Nucl Med Mol Imaging. 2002 Oct;29(10):1317–23. doi: 10.1007/s00259-002-0880-8.

Heudel P, Cimarelli S, Montella A, Bouteille C, Mognetti T. Value of PET-FDG in primary breast cancer based on histopathological and immunohistochemical prognostic factors. Int J Clin Oncol. 2010 Dec;15(6):588–93. doi: 10.1007/s10147-010-0120-3.

Utech CI, Young CS, Winter PF. Prospective evaluation of fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer for the staging of the axilla related to surgery and immunocytochemistry. Eur J Nucl Med. 1996 Dec;23(12):1588–93. doi: 10.1007/BF01249621.

Koo HR, Park JS, Kang KW, Cho N, Chang JM, Bae MS, et al. 18F-FDG uptake in breast cancer correlates with immunohistochemically defined subtypes. Eur Radiol. 2014 Mar;24(3):610–8. doi: 10.1007/s00330-013-3037-1.

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 Dec;34(12):1915–24. doi: 10.9738/INTSURG-D-13-00044.1.

Kumar R, Chauhan A, Zhuang H, Chandra P, Schnall M, Alavi A. Clinicopathologic factors associated with false-negative FDG-PET in primary breast cancer. Breast Cancer Res Treat. 2006 Aug;98(3):267–74. doi: 10.1007/s10549-006-9159-2.

Bitencourt AGV, Lima ENP, Chojniak R, Marques EF, de Souza JA, Graziano L, et al. Correlation between PET/CT results and histological and immunohistochemical findings in breast carcinomas. Radiol Bras. 2014;47(2):67–73. doi: 10.1590/S0100-39842014000200006.

Basu S, Chen W, Tchou J, Mavi A, Cermik T, Czerniecki B, et al. Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization. Cancer. 2008 Mar 1;112(5):995–1000. doi: 10.1002/cncr.23226.

Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomized controlled trial. Lancet Oncol. 2011 Mar;12(3):236–44. doi: 10.1016/S1470-2045(11)70033-X.

Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 2006 Dec 20;24(36):5652–7. doi: 10.1200/JCO.2006.06.5664.

Shimoda W, Hayashi M, Murakami K, Oyama T, Sunagawa M. The relationship between FDG uptake in PET scans and biological behavior in breast cancer. Breast Cancer Tokyo Jpn. 2007;14(3):260–8. doi: 10.2325/jbcs.14.260.

Prospective multicenter study of axillary nodal staging by positron emission tomography in breast cancer: a report of the staging of breast cancer with PET study group. Womens Oncol Rev. 2004 Jun 1;4(2):151–2. doi: 10.1200/JCO.2004.04.148.

Crippa F, Agresti R, Seregni E, Greco M, Pascali C, Bogni A, et al. Prospective evaluation of fluorine-18-FDG PET in the presurgical staging of the axilla in breast cancer. J Nucl Med. 1998 Jan;39(1):4–8.

Inoue T, Yutani K, Taguchi T, Tamaki Y, Shiba E, Noguchi S. Preoperative evaluation of prognosis in breast cancer patients by [(18)F]2-Deoxy-2-fluoro-D-glucose-positron emission tomography. J Cancer Res Clin Oncol. 2004 May;130(5):273–8. doi: 10.1007/s00432-003-0536-5.

Veronesi U, De Cicco C, Galimberti VE, Fernandez JR, Rotmensz N, Viale G, et al. A comparative study on the value of FDG-PET and sentinel node biopsy to identify occult axillary metastases. Ann Oncol. 2007 Mar;18(3):473–8. doi: 10.1093/annonc/mdl425.

Heusner TA, Kuemmel S, Hahn S, Koeninger A, Otterbach F, Hamami ME, et al. Diagnostic value of full-dose FDG PET/CT for axillary lymph node staging in breast cancer patients. Eur J Nucl Med Mol Imaging. 2009 Oct;36(10):1543–50. doi: 10.1007/s00259-009-1145-6.

Authors

Nishita Goyal
Periakaruppan Gokulakrishnan
Arunan Murali
Leena Joseph Dennis
Rajeswaran Rangasami
Bhawna Dev
bhawnadev@sriramachandra.edu.in (Primary Contact)
Author Biographies

Nishita Goyal, Department of Radio-diagnosis, Sri Ramachandra Institute Of Higher Education & Research, Porur, Chennai, India

Department of Radio-diagnosis,

Sri Ramachandra Institute Of Higher Education & Research, Porur,

Chennai, India

Periakaruppan Gokulakrishnan, Department of radio-diagnosis, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai. India

Professor,

Department of radio-diagnosis

Sri Ramachandra Institute of Higher Education and Research, Porur,

Chennai.

Arunan Murali, Department of Radio diagnosis Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India

Professor - Department of Radio diagnosis

Sri Ramachandra Institute of Higher Education and Research, Porur,

Chennai, India

Leena Joseph Dennis, Department of Pathology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India.

Professor, Department of Pathology

Sri Ramachandra Institute of Higher Education and Research, Porur,

Chennai, India.

Rajeswaran Rangasami, Deprtment of Radio-diagnosis Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India.

Professor and Head of the Department, 

Deprtment of Radio-diagnosis

Sri Ramachandra Institute of Higher Education and Research, Porur,

Chennai, India.

Bhawna Dev, Department of Radio-diagnosis, Sri Ramachandra Institute of Higher Education & Research, Porur Chennai, India.

Professor, Department of Radio-diagnosis

Sri Ramachandra Institute of Higher Education & Research, Porur

Chennai, India.

1.
Goyal N, Gokulakrishnan P, Murali A, Dennis LJ, Rangasami R, Dev B. Association of Standardized Uptake Values of Primary Breast Cancer on [18F]FDG PET/CT With Immunohistochemistry and Molecular Subtypes : Correlation of SUV of primary BC with molecular subtypes. Arch Breast Cancer [Internet]. 2023 Mar. 10 [cited 2024 Jul. 14];10(2):175-86. Available from: https://www.archbreastcancer.com/index.php/abc/article/view/668

Article Details

Most read articles by the same author(s)