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CCND1 and FGFR1 gene amplifications are associated with reduced benefit from aromatase inhibitors in metastatic breast cancer

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Abstract

Purpose

Endocrine therapy is a mainstay for the treatment of hormone receptor-positive breast cancer (BC); however, only a fraction of patients experience a pronounced response to antagonists of estrogen signaling. There is a need to identify predictors for efficacy of this treatment.

Methods

This study included 138 patients with newly diagnosed metastatic BC, who received upfront endocrine therapy. Archival biopsy specimens were tested for CCND1 and FGFR1 gene amplification and mRNA expression by PCR-based methods.

Results

CCND1 and FGFR1 amplification was detected in 24 (17.9%) and 28 (20.9%) of 134 evaluable cases, respectively; 9 carcinomas had concurrent alterations of these two genes. Presence of amplification in at least one locus was more common in tumors of higher grade (p = 0.018) and was associated with higher Ki-67 proliferation index (p = 0.036). CCND1 gene amplification was associated with shorter progression-free survival (PFS) in patients receiving aromatase inhibitors (AI) [16.0 months vs. 32.4 months, HR = 3.16 (95% CI 1.26–7.93), p = 0.014]. FGFR1 status did not significantly affect PFS of AI-treated women; however, objective response to AI was observed less frequently in FGFR1-amplified BC as compared to cases with normal FGFR1 copy number [2/15 (13.3%) vs. 22/46 (47.8%), p = 0.031]. Meanwhile, CCND1/FGFR1 gene status did not influence the outcome of tamoxifen-treated patients.

Conclusion

Presence of CCND1 and/or FGFR1 amplification is associated with worse outcomes of AI therapy in patients with metastatic BC.

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Data availability

The data generated and analyzed during the current study are included in the article and its supplementary information files.

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Funding

The study was funded by the Russian Science Foundation (grant number 19-15-00207).

Author information

Authors and Affiliations

  1. Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Saint-Petersburg, Russia, 197758

    S. N. Aleksakhina, A. D. Mikushina, S. E. Kubrina, A. O. Ivantsov, E. N. Imyanitov & A. G. Iyevleva

  2. City Cancer Center, Saint-Petersburg, Russia, 197758

    M. M. Kramchaninov & V. M. Moiseyenko

  3. Saint-Petersburg Pediatric Medical University, Saint-Petersburg, Russia, 194100

    E. N. Imyanitov & A. G. Iyevleva

  4. Sverdlovskiy Regional Oncological Hospital, Ekatherinburg, Russia, 620036

    V. V. Petkau

  5. I.I. Mechnikov North-Western Medical University, Saint-Petersburg, Russia, 191015

    E. N. Imyanitov

Authors
  1. S. N. Aleksakhina
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  2. M. M. Kramchaninov
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  3. A. D. Mikushina
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  4. S. E. Kubrina
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  5. V. V. Petkau
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  6. A. O. Ivantsov
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  7. V. M. Moiseyenko
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  8. E. N. Imyanitov
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  9. A. G. Iyevleva
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Contributions

Conceptualization and supervision: ENI, AGI; Methodology: ADM, SEK; Formal analysis and investigation: SNA, MMK, VVP, AOI, VMM; Writing—original draft preparation: AGI; Writing—review and editing: all authors.

Corresponding author

Correspondence to A. G. Iyevleva.

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Conflict of interest

All authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional Ethical Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Aleksakhina, S.N., Kramchaninov, M.M., Mikushina, A.D. et al. CCND1 and FGFR1 gene amplifications are associated with reduced benefit from aromatase inhibitors in metastatic breast cancer. Clin Transl Oncol 23, 874–881 (2021). https://doi.org/10.1007/s12094-020-02481-w

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  • DOI: https://doi.org/10.1007/s12094-020-02481-w

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