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Review
. 2021 May 27;13(11):2640.
doi: 10.3390/cancers13112640.

Circulating Biomarkers of CDK4/6 Inhibitors Response in Hormone Receptor Positive and HER2 Negative Breast Cancer

Ilenia Migliaccio  1 , Angela Leo  1 , Francesca Galardi  1 , Cristina Guarducci  2 , Giulio Maria Fusco  1 , Matteo Benelli  3 , Angelo Di Leo  4 , Laura Biganzoli  4 , Luca Malorni  1   4
Affiliations
Review

Circulating Biomarkers of CDK4/6 Inhibitors Response in Hormone Receptor Positive and HER2 Negative Breast Cancer

Ilenia Migliaccio et al. Cancers (Basel). .

Abstract

CDK4/6 inhibitors (CDK4/6i) and endocrine therapy are the standard treatment for patients with hormone receptor-positive and HER2 negative (HR+/HER2-) metastatic breast cancer. Patients might show intrinsic and acquired resistance, which leads to treatment failure and progression. Circulating biomarkers have the potential advantages of recognizing patients who might not respond to treatment, monitoring treatment effects and identifying markers of acquired resistance during tumor progression with a simple withdrawal of peripheral blood. Genomic alterations on circulating tumor DNA and serum thymidine kinase activity, but also circulating tumor cells, epigenetic or exosome markers are currently being tested as markers of CDK4/6i treatment response, even though none of these have been integrated into clinical practice. In this review, we discuss the recent advancements in the development of circulating biomarkers of CDK4/6i response in patients with HR+/HER2-breast cancer.

Keywords: CDK4/6 inhibitors; breast cancer; circulating biomarkers; liquid biopsy; therapy resistance.

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Conflict of interest statement

I Migliaccio, A Leo, F Galardi, C Guarducci, GM Fusco: None; M Benelli: Consultant honoraria: Novartis; L Biganzoli: Personal financial interests (honoraria, consulting or advisory role): AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Genomic Health, Ipsen, Lilly, Novartis, Pfizer, Pierre Fabre, Roche, Takeda. Institutional financial interests: Celgene, Genomic Health, Novartis; A Di Leo: Personal financial interests (honoraria, consulting or advisory role): Amgen, AstraZeneca, Athenex, Bayer, Celgene, Daiichi-Sankyo, Eisai, Genentech, Genomic Health, Ipsen, Lilly, Novartis, Pfizer, Pierre Fabre, Puma Biotechnology, Roche, Seattle Genetics, Sellas Life Sciences Group. Institutional financial interests: Novartis; L. Malorni: Speaker/consultant honoraria: Novartis, Pfizer, Lilly. Research Grant: Novartis, Pfizer. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Schematic illustration of some of the potential circulating biomarkers of response to CDK4/6i in HR+/HER2− BC discussed in this review (TK1 = thymidine kinase 1; SNV = single nucleotide variations; CNA = copy number alterations).
See this image and copyright information in PMC

References

    1. Migliaccio I., Malorni L., Hart C.D., Guarducci C., Di Leo A. Endocrine therapy considerations in postmenopausal patients with hormone receptor positive, human epidermal growth factor receptor type 2 negative advanced breast cancers. BMC Med. 2015;13:46. doi: 10.1186/s12916-015-0280-0. - DOI - PMC - PubMed
    1. Pan H., Gray R., Braybrooke J., Davies C., Taylor C., McGale P., Peto R., Pritchard K.I., Bergh J., Dowsett M., et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N. Engl. J. Med. 2017;377:1836–1846. doi: 10.1056/NEJMoa1701830. - DOI - PMC - PubMed
    1. Finn R.S., Crown J.P., Lang I., Boér K., Bondarenko I.M., Kulyk S.O., Ettl J., Patel R., Pinter T., Schmidt M., et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): A randomised phase 2 study. Lancet Oncol. 2015;16:25–35. doi: 10.1016/S1470-2045(14)71159-3. - DOI - PubMed
    1. Turner N.C., Ro J., André F., Loi S., Verma S., Iwata H., Harbeck N., Loibl S., Bartlett C.H., Zhang K., et al. Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer. N. Engl. J. Med. 2015;373:209–219. doi: 10.1056/NEJMoa1505270. - DOI - PubMed
    1. Finn R.S., Martin M., Rugo H.S., Jones S., Im S.-A., Gelmon K., Harbeck N., Lipatov O.N., Walshe J.M., Moulder S., et al. Palbociclib and Letrozole in Advanced Breast Cancer. N. Engl. J. Med. 2016;375:1925–1936. doi: 10.1056/NEJMoa1607303. - DOI - PubMed