THE PROGNOSTIC SIGNIFICANCE OF BRCA1 GENE EXPRESSION IN PATIENTS WITH BREAST CANCER
PDF (Русский)

Keywords

BRCA1
BREAST CANCER
EXPRESSION
NONMETASTATIC SURVIVAL
FORECAST
LACK OF HOMOLOGOUS RECOMBINATION

How to Cite

Tsyganov, M., Ibragimova, M., Deryusheva, I., Garbukov, Y., Kazantseva, P., Pevzner, A., Slonimskaya, Y., & Litvyakov, N. (2019). THE PROGNOSTIC SIGNIFICANCE OF BRCA1 GENE EXPRESSION IN PATIENTS WITH BREAST CANCER. Voprosy Onkologii, 65(3), 368–373. https://doi.org/10.37469/0507-3758-2019-65-3-368-373

Abstract

Nowadays, BRCA-associated breast cancer occupies a special position in the choice of treatment strategy. Although, the drug treatment of such patients was almost the same as the treatment of sporadic disease. Of particular interest is the assessment of the deficit of homologous recombination, which may include various dysfunctions of the BRCA1 gene. Moreover, it has been shown that a decrease in the functional activity of BRCA1 is reflected in the sensitivity of the tumor to DNA damaging agents, and the prognosis of the disease becomes more favorable.

Aim: assessment of the association of BRCA1 gene expression in a breast tumor with the prognosis of the disease.

Materials and methods. The study included 111 patients with breast cancer T1-4N0-3M0 (stage IIA - IIIB), with a morphologically verified diagnosis. Initial and postoperative expression of BRCA1 in tumor material was evaluated. RNA was isolated from the tumor material before treatment and after NAC. The level of BRCA1 expression was assessed using reverse transcriptase quantitative real-time PCR (RT-qPCR).

Results. As a result of the study, long-term results of treatment of patients were evaluated depending on the level of BRCA1 gene expression. The presence of BRCA1 hypoexpression (level less than 1) in tumor tissue after NAC was found to be a favorable prognostic factor and is associated with high rates of metastasis-free survival (p=0.0002). In addition, a similar result is shown for patients treated with the FAC NAC regimen (p=0.005). An interesting result was demonstrated for 8 patients who underwent chemotherapy with the inclusion of platinum drugs. All patients had a low postoperative expression level of BRCA1 and 100% non-metastatic and overall survival.

Conclusion. Thus, the data obtained indicate the prognostic significance of BRCA1 gene expression in a breast tumor after neoadjuvant chemotherapy.

https://doi.org/10.37469/0507-3758-2019-65-3-368-373
PDF (Русский)

References

Имянитов ЕН. Молекулярная диагностика в онкологии // Вопросы онкологии. - 2012. - 58. - C. 153-163.

Zhong Q., Peng H.L., Zhao X. et al. Effects of BRCA1-and BRCA2-related mutations on ovarian and breast cancer survival: a meta-analysis // Clinical Cancer Research. - 2015. - Vol. 21. - P. 211-220. - CCR-14-1816. DOI: 10.1158/1078-0432

Afghahi A., Timms K.M., Vinayak S. et al. Tumor BRCA1 reversion mutation arising during neoadjuvant platinum-based chemotherapy in triple-negative breast cancer is associated with therapy resistance // Clinical Cancer Research. - 2017. - Vol. 1. - P 1-26. - DOI: 10.1158/1078-0432.CCR-16-2174

Gerratana L., Fanotto V., Pelizzari G. et al. Do platinum salts fit all triple negative breast cancers? // Cancer treatment reviews. - 2016. - Vol. 48. - P. 34-41. - DOI: 10.1016/j.ctrv.2016.06.004

Mccabe N., Turner N.C., Lord C.J. et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly (ADP-ribose) polymerase inhibition // Cancer research. - 2006. - Vol. 66. - P. 8109-8115. - DOI: 10.1158/0008-5472.CAN-06-0140

Schwartz G.F., Hortobagyi G.N. Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26-28, 2003, Philadelphia, Pennsylvania // The Breast Journal. - 2004. - Vol. 10. - P. 273-294. - DOI: 10.111Vj.1075-122X.2004.21594.x.

Pfaffl M.W. A new mathematical model for relative quantification in real-time RT-PCR // Nucleic acids research. - 2001. - Vol. 29. - P 45. - DOI: 10.1093/nar/29.9.e45

Гафтон И.Г., Имянитов Е.Н., Семиглазов В.В. и др. Экспрессия гена BRCA1 при нейроэндокринных опухолях желудочно-кишечного тракта // Сибирский онкологический журнал. - 2014. - Т. 16. - С. 11-15.

Imyanitov E.N., Moiseyenko V.M. Drug therapy for hereditary cancers // Hereditary cancer in clinical practice. - 2011. - Vol. 9. - P 1-16. - DOI: 10.1186/1897-4287-9-5

Kurebayashi J., Yamamoto Y, Kurosumi M. et al. Loss of BRCA1 expression may predict shorter time-to-progression in metastatic breast cancer patients treated with taxanes // Anticancer research. - 2006. - Vol. 26. - P. 695-701.

Tsibulak I., Shivalingaiah G., Wenzel S. et al. Clinical impact of BRCA1 and BRCA2 mRNA expression in ovarian cancer // American Society of Clinical Oncology. - 2018. - Vol. 36. - e17533. - suppl.e17533. DOI: 10.1200/jm.2018.36.15_

Nomura H., Kataoka F., Aoki D. et al. Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triplenegative breast cancer // Cancer Biomarkers. - 2016. - Vol. 16. - P 145-152. - DOI: 10.3233/CBM-150550

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