Molecular imaging to identify patients with metastatic breast cancer who benefit from endocrine treatment combined with cyclin-dependent kinase inhibition. (February 2020)

• Record Type: Journal Article
• Authors: Boers, Jorianne; Venema, Clasina M.; de Vries, Erik F.J.; Glaudemans, Andor W.J.M.; Kwee, Thomas C.; Schuuring, Ed; Martens, John W.M.; Elias, Sjoerd G.; Hospers, Geke A.P.; Schröder, Carolina P.
• Is Part Of: European journal of cancer. Volume 126(2020)
• Page Start: 11
• Page End: 20
• Publication Date: 2020-02
• Subjects: CDK inhibition -- Endocrine therapy -- Biomarker -- FES-PET -- Heterogeneity -- Breast cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2019.10.024
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Adding cyclin-dependent kinase (CDK) inhibitor to endocrine treatment improves outcome in œstrogen receptor (ER) positive metastatic breast cancer, but identifying the subset of patients who benefit is challenging. Response is potentially associated with ER expression heterogeneity. This is because, unlike the primary tumour in the breast that is localized to the organ, the metastatic breast cancer has spread and continues to spread to distant locations in the body such as bones, lungs, liver, axial skeleton, even to the central nervous system like the brain, wherefrom obtaining biopsies are not easy, and also, the metastasised tissues are heterogeneous. Positron emission tomography (PET) with 16α-[ 18 F]fluoro-17β-œstradiol (FES), briefly referred to as FES-PET, allows whole-body ER assessment. We explored whether FES-PET heterogeneity and FES uptake were related to letrozole and palbociclib outcome, in patients with ER positive, metastatic breast cancer. Patients and methods: Patients underwent a baseline FES-PET and 18 F-fluorodeoxyglucose (FDG) PET, the FDG-PET served to help identify active sites of breast cancer with contrast-enhanced computed tomography (CT). FES-PET heterogeneity score (% FES positive lesions divided by all lesions on FDG-PET and/or CT) and FES uptake were related to outcome and 8-week FDG-PET response. Circulating tumour DNA (CtDNA) samples for ESR1 mutation analysis were collected at baseline. Results: In 30 patients with 864 metastatic lesions, baseline FES-PET heterogeneity was assessed. In 27 patients with 688 lesions, response was evaluated. Median time to progression (TTP) was 73 weeks (95% confidence interval [CI] 21 to ∞) in 7 patients with 100% FES positive disease, 27 weeks (14–49) in heterogeneous FES positive disease (20 patients), and 15 weeks (9 to ∞) without FES positivity (three patients; log-rank P = 0.30). Geometric mean FES uptake was 2.3 for metabolic progressive patients, 2.5 ( P vs progression = 0.82) for metabolic stable disease, and 3.3 ( P vs progression = 0.40) for metabolic response ( P trend = 0.21). ESR1 mutations, found in 13/23 patients, were unrelated to FES uptake. Conclusion: This exploratory study suggests that FES-PET heterogeneity may potentially identify the subset of ER positive, metastatic breast cancer patients who benefit from letrozole combined with CDK inhibition. Clinical trial information: NCT02806050 . Highlights: Endocrine treatment with CDK-i does not benefit breast cancer patients equally. Oestrogen receptor (ER) heterogeneity can be assessed with FES- and FDG-PET. With ER positive homogeneity, combined treatment response is longer than with heterogeneity. FES- and FDG-PET may identify patients with most combined treatment benefit.