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. 2024;20(32):2457-2466.
doi: 10.1080/14796694.2024.2377531. Epub 2024 Jul 29.

The NEOLETRIB trial: neoadjuvant treatment with Letrozole and Ribociclib in ER-positive, HER2-negative breast cancer

Kamilla Fjermeros  1 , Salim Ghannoum  2 , Stephanie B Geisler  1 , Sameer Bhargava  1   3 , Andliena Tahiri  4 , Jovana Klajic  4 , Torben Lüders  4   5 , Marie Fongård  2 , Meh Sameen Nawaz  4   6 , Tatjana Bosnjak-Olsen  7 , Unn-Cathrin Edvardsen Buvarp  1 , Aino Katri Johanna Rosenskiold  1 , Nam Thi Nguyen  1 , Tone Tysko Sletbak  1 , Manouchehr Seyedzadeh  8 , Knut Selsås  9 , Alina Carmen Porojnicu  10 , Helle Kristine Skjerven  11 , Tone Hovda  12 , Kristine Kleivi Sahlberg  13   5 , Lilly Anne Torland  13   5 , Marianne Lyngra  14 , Clara Louise Hammarström  14 , Elma Bahonjic Hönigsperger  14 , John Christopher Noone  14 , Silje Mathiassen  14 , Antoni Hurtado  15 , Shom Goel  16 , Andrew Koff  17 , Xavier Tekpli  2 , Vessela N Kristensen  2   5 , Jürgen Geisler  1   5
Affiliations

The NEOLETRIB trial: neoadjuvant treatment with Letrozole and Ribociclib in ER-positive, HER2-negative breast cancer

Kamilla Fjermeros et al. Future Oncol. 2024.

Abstract

Chemotherapy is used as neoadjuvant therapy for all subgroups of breast cancer, including ER-positive, and HER2-negative cases. However, studies have suggested that using aromatase inhibitors combined with CDK4/6-inhibitors might be an appropriate alternative in selected patients. Thus, the NEOLETRIB trial evaluates the response of ER-positive, HER2-negative luminal A/B breast cancer to the combination of letrozole and ribociclib in the neoadjuvant setting. Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Our findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination and give new insights into the intra-tumoral changes during this treatment.Trial registration number: NCT05163106 (ClinicalTrials.gov).

Keywords: HR positive; gut microbiome; letrozole; locally advanced breast cancer; neoadjuvant; ribociclib; senescence; single-cell RNA sequencing.

Plain language summary

[Box: see text].

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Conflict of interest statement

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Design and timeline of the NEOLETRIB trial. All patients will be treated with Letrozole and Ribociclib, with the addition of Goserelin to pre- and perimenopausal patients. At baseline written consent will be collected and staging procedures will be performed. The first MRI/CT breast will be done as well as the first tumor biopsy and biobanking of blood samples, liquid biopsies and feces samples. Biobanking procedures will be repeated on day 21 of cycles 1, 3 and 6 of ribociclib treatment. MRI/CT breast will be repeated on day 21 of cycles 3 and 6 of ribociclib treatment. C1 D21: Cycle 1 day 21. C3 D21: Cycle 3 day 21. C6 D21: Cycle 6 day 21.
Figure 2.
Figure 2.
Molecular biology procedures and techniques to be used in the NEOLETRIB trial. PDEC: Patient-derived explant culture; WES: Whole exosome sequencing; WGS: Whole genome sequencing.
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, et al. . Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660 - DOI - PubMed
    1. Aebi S, Karlsson P, Wapnir IL. Locally advanced breast cancer. Breast. 2022;62(Suppl. 1):S58–S62. doi:10.1016/j.breast.2021.12.011 - DOI - PMC - PubMed
    1. Thompson AM, Moulder-Thompson SL. Neoadjuvant treatment of breast cancer. Ann Oncol. 2012;23(Suppl. 10):x231–x236. doi:10.1093/annonc/mds324 - DOI - PMC - PubMed
    1. Geisler J, Smith I, Miller W. Presurgical (neoadjuvant) endocrine therapy is a useful model to predict response and outcome to endocrine treatment in breast cancer patients. J Steroid Biochem Mol Biol. 2012;131(3–5):93–100. doi:10.1016/j.jsbmb.2011.12.006 - DOI - PubMed
    1. Miller WR, Larionov A. Changes in expression of oestrogen regulated and proliferation genes with neoadjuvant treatment highlight heterogeneity of clinical resistance to the aromatase inhibitor, letrozole. Breast Cancer Res. 2010;12(4):R52. doi:10.1186/bcr2611 - DOI - PMC - PubMed

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