Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

4272 - Expression of TK1 and CDK9 in plasma-derived exosomes is associated with clinical response to CDK4/6 inhibitors in breast cancer

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Translational Research

Tumour Site

Breast Cancer

Presenters

Stefania Crucitta

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

S. Crucitta1, M. Del Re1, A. Fontana2, I. Bertolini2, E. Rofi1, C. De Angelis2, L. Diodati2, D. Cavallero2, B. Salvadori2, A. Falcone2, R. Morganti3, R. Danesi1

Author affiliations

  • 1 Clinical And Experimental Medicine, University of Pisa, 56126 - Pisa/IT
  • 2 Medical Oncology Unit, Department Of Translational Research And New Technologies In Medicine And Surgery, University of Pisa, Pisa, Italy, 56126 - Pisa/IT
  • 3 Section Of Statistics, University of Pisa, 56100 - Pisa/IT
More

Resources

Abstract 4272

Background

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve PFS in patients with hormone receptor-positive (HR+) advanced breast cancer (Finn et al., 2016). In order to better characterize the response to these agents and increase our knowledge on the pharmacogenetic profile of CDK4/6i, the aim of this study was to analyse the expression of targets relevant to the activity of CDK4/6i in plasma-derived exosomes.

Methods

Blood samples were collected from patients affected by HR+, HER2- advanced breast cancer receiving palbociclib/ribociclib in association with hormonal therapy. Three ml of plasma were taken at the beginning of treatment (baseline) and at the first clinical evaluation (after 3 months). Objective responses were defined following the RECIST criteria v.1.1. RNA from plasma-derived exosomes was extracted by the ExoRNeasy kit (Qiagen) and analysed for the expression of thymidine kinase 1 (TK1), CDK 4, 6 and 9 by digital droplet PCR (BioRad). Mann-Whitney test was applied.

Results

Thirty-four metastatic breast cancer patients were prospectively enrolled in this study. The comparison of mRNA levels of TK1, CDK4, 6 and 9 between baseline and the first clinical evaluation was available in 22 patients treated with letrozole/anastrozole + palbociclib and 22 patients given fulvestrant + palbociclib. 18 patients had newly diagnosed advanced breast cancer while 16 patients received ≥1 line of treatment. Objective responses were: 1 (2,9%) CR, 4 (11,8%) PR, 16 (47,1%) SD and 13 (38,2%) PD. The comparison of changes in the expression between TK1, CDK 4, 6 and 9 at baseline compared to first evaluation was statistically significant for TK1 (PR+SD vs. PD p = 0.009), CDK4 (PR+SD vs. PD p = 0.020), CDK6 (PR+SD vs. PD p = 0.047) and CDK9 (PR+SD vs. PD p = 0.008). The univariate analysis didn’t find any significant correlation between patients clinical variable and PFS (i.e. type of hormonal treatment, the line of treatment, performance and menopausal status, visceral metastasis, bone only metastasis, number of metastasis, previous hormonal or lines of chemotherapy received).

Conclusions

Exosomal expression of CDK4, CDK6 and in particular of TK1 and CDK9 may be useful to early identify patients who are likely to respond to CDK4/6i.

Clinical trial identification

Legal entity responsible for the study

Romano Danesi.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.