CNA landscape of HER2-negative breast cancer during administration of taxane-containing schemes of neoadjuvant chemotherapy

Introduction. Evaluation of when and how to include taxanes in preoperative chemotherapy is becoming more important in the era when molecular and genetic approaches allow to develop biologically targeted therapeutic medications and select patients who can benefit from certain cytotoxic agents.
Aim. To analyze the use of CNA genetic landscape (CNA – copy number aberration) luminal B HER2-negative (HER2 – human epidermal growth factor receptor type 2) breast cancer during taxane-containing neoadjuvant chemotherapy (NCT) for identification of the groups of potential CNA markers of objective response to treatment and CNA markers of prognosis of hematogenous metastases.
Materials and methods. The study included 28 patients with luminal B HER2-negative breast cancer T1–4N0–3M0 stage IIA–IIIB aged 24–67 years (mean age 44.6 ± 0.3 years). In neoadjuvant regimen, the patients received 4–8 courses of chemotherapy per the ACT, AT schemes and taxotere as monotherapy. As study samples, paired tumor biopsies taken prior to treatment under ultrasound control and operative material after neoadjuvant therapy were used. Micromatrix analysis was performed using high density DNA CytoScanTM HD Array (Affymetrix, uSA). The results were processed using Chromosome Analysis Suite 4.0 (Affymetrix, uSA) software. Statistical data processing was performed in Statistica 8.0 (StatSoft Inc., uSA) software.
Results. Objective response was observed in the absence of amplification in the 20q11.22 (р = 0.003) region and presence of amplifications in the 16p13.2 (р = 0.027) locus in the tumor prior to treatment. After NCT, hematogenous metastases developed in the tumor in the presence of a small number of amplifications in the 20q13.33 (р = 0.002) locus.
Conclusion. Potential predictive CNA markers of objective response to treatment and prognostic CNA markers of hematogenous metastases during administration of taxane-containing schemes of neoadjuvant chemotherapy were identified.

1. Rašić A., Sofić A., Bešlija S. et al. Effects of adding taxane to anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer. Med Glas (Zenica) 2019;16(1):1–6. DOI: 10.17392/964-19

2. Lai J.-I., Chao T.-C., Liu C.-Y. et al. A systemic review of taxanes and their side effects in metastatic breast cancer. Front Oncol 2022;12:940239. DOI: 10.3389/fonc.2022.940239

3. Earl H.M., Vallier A.L., Hiller L. et al. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2x2 factorial randomised phase 3 trial. Lancet Oncol 2014;15(2):201–12. DOI: 10.1016/S1470-2045(13)70554-0

4. Orsaria P., Grasso A., Ippolito E. et al. Clinical outcomes among major breast cancer subtypes after neoadjuvant chemotherapy: impact on breast cancer recurrence and survival. Anticancer Res 2021;41(5):2697–709. DOI: 10.21873/anticanres.15051

5. Maloney S.M., Hoover C.A., Morejon-Lasso L.V. et al. Mechanisms of taxane resistance. Cancers 2020;12(11):3323. DOI: 10.3390/cancers12113323

6. Das T., Anand U., Pandey S.K. et al. Therapeutic strategies to overcome taxane resistance in cancer. Drug Resistance Updates 2021;55:100754. DOI: 10.1016/j.drup.2021.100754

7. Jivani A., Shinde R.K. A comprehensive review of taxane treatment in breast cancer: clinical perspectives and toxicity profiles. Cureus 2024;16(4):e59266. DOI: 10.7759/cureus.59266

8. Cardoso F., Senkus E., Costa A. et al. 4th ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 4). Ann Oncol 2018;29(8):1634–57. DOI: 10.1093/annonc/mdy192

9. Korde L.A., Somerfield M.R., Carey L.A. et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol 2021;39(13):1485–505. DOI: 10.1200/JCO.20.03399

10. Sparano J.A., Gray R.J., Makower D.F. et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 2018;379:111–21. DOI: 10.1056/nejmoa1804710

11. Chang J.C., Makris A., Gutierrez M.C. et al. Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients. Br Cancer Res Treat 2008;108(2):233–40. DOI: 10.1007/s10549-007-9590-z

12. Soran A., Bhargava R., Johnson R. et al. The impact of Oncotype DX(R) recurrence score of paraffin-embedded core biopsy tissues in predicting response to neoadjuvant chemotherapy in women with breast cancer. Breast Dis 2016;36:65–71. DOI: 10.3233/bd-150199

13. Tesch M.E., Chia S.K., Simmons C.E. et al. Impact of sequence order of anthracyclines and taxanes in neoadjuvant chemotherapy on pathologic complete response rate in HER2-negative breast cancer patients. Breast Cancer Res Treat 2021;187(1):167–76. DOI: 10.1007/s10549-021-06110-0

14. Tyulyandin S.A., Artamonova E.V., Zhigulev A.N. et al. Practical recommendations for drug treatment of breast cancer. Zlokachestvennye opuholi = Malignant Tumors 2023;13(3s2-1): 157–200. (In Russ.). DOI: 10.18027/2224-5057-2023-13-3s2-1-157-200

15. Jia G., Ping J., Shu X. et al. Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics. AJHG 2022;109(12):2185–95. DOI: 10.1016/j.ajhg.2022.10.011

16. Shao Z., Ma X., Zhang Y. et al. CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple-negative breast cancer. Mol Carcinog 2020;59(5):533–44. DOI: 10.1002/mc.23177

17. Sheng G., Li F., Jin W., Wang K. Pan-caner analysis identifies PSMA7 as a targets for amplification at 20q13.33 in tumorigenesis. Sci Rep 2024;14:3034. DOI: 10.1038/s41598-024-53585-0

18. Padmanabhan A., Vuong S.A., Hochstrasser M. Assembly of an evolutionarily conserved alternative proteasome isoform in human cells. Cell Rep 2016;14(12):2962–74. DOI: 10.1016/j.celrep.2016.02.068

19. Xiao Y., Zhang S.J., Yan X. et al. MiR-466 as a poor prognostic predictor suppresses cell proliferation and EMT in breast cancer cells by targeting PSMA7. Eur Rev Med Pharmacol Sci 2022;26(11):3799. DOI: 10.26355/eurrev_202206_28946