Evaluation of tumour heterogeneity by <sup>18</sup>F-fluoroestradiol PET as a predictive measure in breast cancer patients receiving palbociclib combined with endocrine treatment

Author(s): Cheng Liu ¹ ^, ³ ^, ⁴ ^, ⁵ ^, ⁶ , Shihui Hu ² ^, ³ , Xiaoping Xu ¹ ^, ³ ^, ⁵ ^, ⁶ , Yongping Zhang ¹ ^, ³ ^, ⁵ ^, ⁶ , Biyun Wang ² ^, ³ ^, , Shaoli Song ¹ ^, ³ ^, ⁴ ^, ⁵ ^, ⁶ ^, , Zhongyi Yang ¹ ^, ³ ^, ⁵ ^, ⁶ ^,

Publication date (Electronic): 26 August 2022

Journal: Breast Cancer Research : BCR

Publisher: BioMed Central

Keywords: 18F-FES, Tumour heterogeneity, Palbociclib, Endocrine therapy, Metastatic breast cancer

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Abstract

Background

Predictive biomarkers are needed to identify oestrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer (MBC) patients who would likely benefit from cyclin-dependent kinase 4 and 6 inhibitors combined with endocrine therapy. Therefore, we performed an exploratory study to evaluate the tumour heterogeneity parameters based on 16α- ¹⁸F-fluoro-17β-oestradiol ( ¹⁸F-FES)-PET imaging as a potential marker to predict progression-free survival (PFS) in MBC patients receiving palbociclib combined with endocrine therapy.

Methods

Fifty-six ER + MBC patients underwent ¹⁸F-FES-PET/CT before the initiation of palbociclib. ¹⁸F-FES uptake was quantified and expressed as the standardized uptake value (SUV). Interlesional heterogeneity was qualitatively identified according to the presence or absence of ¹⁸F-FES-negative lesions. Intralesional heterogeneity was measured by the SUV-based heterogeneity index (HI = SUVmax/SUVmean). Association with survival was evaluated using the Cox proportional hazards model.

Results

A total of 551 metastatic lesions were found in 56 patients: 507 lesions were identified as ¹⁸F-FES-positive, 38 lesions were distributed across 10 patients without ¹⁸F-FES uptake, and the remaining 6 were liver lesions. Forty-three patients obtained a clinical benefit, and 13 developed progressive disease (PD) within 24 weeks. Nine out of 10 patients with an ¹⁸F-FES-negative site developed PD, and the median PFS was only 2.4 months. Among 46 patients with only ¹⁸F-FES-positive lesions, only four patients had PD, and the median PFS was 23.6 months. There were statistically significant differences between the two groups ( P < 0.001). For the subgroup of patients with only ¹⁸F-FES-positive lesions, low FES-HI patients experienced substantially longer PFS times than those with high FES-HI (26.5 months vs. 16.5 months, P = 0.004).

Conclusions

¹⁸F-FES-PET may provide a promising method for identifying and selecting candidate ER + /HER2- MBC patients who would most likely benefit from palbociclib combined with endocrine treatment and could serve as a predictive marker for treatment response.

Trial registration NCT04992156, Date of registration: August 5, 2021 (retrospectively registered).

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Author and article information

Contributors

Biyun Wang: wangbiyun0107@hotmail.com

Shaoli Song: shaoli-song@163.com

Zhongyi Yang:

ORCID: http://orcid.org/0000-0001-6195-9942

yangzhongyi21@163.com

Journal

Journal ID (nlm-ta): Breast Cancer Res

Journal ID (iso-abbrev): Breast Cancer Res

Title: Breast Cancer Research : BCR

Publisher: BioMed Central (London )

ISSN (Print): 1465-5411

ISSN (Electronic): 1465-542X

Publication date (Electronic): 26 August 2022

Publication date PMC-release: 26 August 2022

Publication date (Print): 2022

Volume: 24

Electronic Location Identifier: 57

Affiliations

[1 ]GRID grid.452404.3, ISNI 0000 0004 1808 0942, Department of Nuclear Medicine, , Fudan University Shanghai Cancer Center, ; No.270, Dong’an Road, Xuhui District, Shanghai, 200032 China

[2 ]GRID grid.452404.3, ISNI 0000 0004 1808 0942, Department of Medical Oncology, , Fudan University Shanghai Cancer Center, ; Shanghai, 200032 China

[3 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Department of Oncology, Shanghai Medical College, , Fudan University, ; Shanghai, 200032 China

[4 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Shanghai Institute of Medical Imaging, , Fudan University, ; Shanghai, 200032 China

[5 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Center for Biomedical Imaging, , Fudan University, ; Shanghai, 200032 China

[6 ]Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, 200032 China

Author information

Zhongyi Yang http://orcid.org/0000-0001-6195-9942

Article

Publisher ID: 1555

DOI: 10.1186/s13058-022-01555-7

PMC ID: 9419349

PubMed ID: 36028895

SO-VID: ba6a124d-3d6e-4408-89b1-eee6f7b37abb

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 3 November 2021

Date accepted : 16 August 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81874114

Award Recipient : Biyun Wang

Funded by: Shanghai Sailing Program

Award ID: 20YF1408500

Award Recipient : Cheng Liu

Funded by: Shanghai Committee of Science and Technology Fund

Award ID: 19ZR1411300

Award Recipient : Zhongyi Yang

Funded by: Shanghai Municipal Health Commission

Award ID: 202040269

Award Recipient : Zhongyi Yang

Funded by: Science and Technology Development Fund of Shanghai Pudong New Area

Award ID: PKJ2020-Y54

Award Recipient : Cheng Liu

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: 18f-fes,tumour heterogeneity,palbociclib,endocrine therapy,metastatic breast cancer

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: 18f-fes, tumour heterogeneity, palbociclib, endocrine therapy, metastatic breast cancer