O.S. Pridko1,2, A.V. Rusyn1,2

1Uzhhorod National University,

2MNE «Transcarpathian Antitumor Center», Uzhhorod, Ukraine


Summary. Hormone-dependent malignant neoplasms are the most common form of breast cancer (BC) worldwide. The high heterogeneity of clinical manifestations and response to treatment indicates the need to search for prognostic and predictive markers to predict the aggressiveness of the course of hormone-dependent BC and prescribe individualized treatment tactics. MicroRNAs are short RNA molecules that play an important role in regulating the expression of many genes. This is due to the fact that miRNAs are important modulators of growth, differentiation and metastasis of malignant neoplasms of various histogenesis, including BC. MicroRNAs can be used to predict the course of the disease and choose optimal treatment tactics, since their levels can be determined not only in tumor tissue but also in blood serum. The systematization and generalization of the results of our own research and data from the literature on the possibility of using miRNA as predictive markers of hormone-dependent BC indicates the perceptiveness of using miRNA to monitor the course of the tumor process and to determine the sensitivity of tumors to neoadjuvant hormonal therapy.

Keywords: breast cancer, neoadjuvant hormone therapy, predictive markers, miRNA



  1. Fedorenko ZP, Goulak LO, Gorokh YL, et al. Cancer in Ukraine, 2021–2022. Incidence, mortality, prevalence and other relevant statistics. Bulletin of the National Cancer Registry of Ukraine. Kyiv, 2023. 24.
  2. Kovalev OO, Kostyuk OG, Tkachuk TV. War as a risk factor for breast cancer. 2023.
  3. Jafari SH, Saadatpour Z, Salmaninejad A, et al. Breast cancer diagnosis: Imaging techniques and biochemical markers. J cell physiol 2018; 233 (7): 5200–13.
  4. Mathur P, Sathishkumar K, Chaturvedi M, et al. Cancer statistics, 2020: report from national cancer registry programme India. JCO Glob Oncol 2020; 6: 1063–75. doi: 10.1200/GO.20.00122.
  5. Ko NY, Hong S, Winn RA, Calip GS. Association of insurance status and racial disparities with the detection of early-stage breast cancer. JAMA oncol 2020; 6 (3): 385–92. doi: 10.1001/jamaoncol.2019.5672.
  6. Fedorenko Z, et al. Cancer in Ukraine, 2020–2021. Incidence, mortality, prevalence and other relevant statistics. Bulletin of the National Cancer Registry of Ukraine. Kyiv, 2022. 23.
  7. Garg PK, Prakash G. Current definition of locally advanced breast cancer. Curr Oncol 2015; 22 (5): 409–10. doi: 10.3747/co.22.2697.
  8. Acar E, Turgut B, Yigit S, Kaya G. Comparison of the volumetric and radiomics findings of 18F-FDG PET/CT images with immunohistochemical prognostic factors in local/locally advanced breast cancer. Nucl Med Commun 2019; 40 (7): 764–72. doi: 10.1097/MNM.0000000000001019.
  9. Klein J, Tran W, Watkins E, et al. Locally advanced breast cancer treated with neoadjuvant chemotherapy and adjuvant radiotherapy: a retrospective cohort analysis. BMC cancer 2019; 19 (1): 1–11. doi: 10.1186/s12885-019-5499-2.
  10. Shenkier T, Weir L, Levine M, et al. Clinical practice guidelines for the care and treatment of breast cancer: 15. Treatment for women with stage III or locally advanced breast cancer. CMAJ 2004; 170 (6): 983–94. doi: 10.1503/cmaj.1030944.
  11. Madigan LI, Dinh P, Graham JD. Neoadjuvant endocrine therapy in locally advanced estrogen or progesterone receptor-positive breast cancer: determining the optimal endocrine agent and treatment duration in postmenopausal women—a literature review and proposed guidelines. Breast Cancer Res 2020. 22 (1), 1-13. doi: 10.1186/s13058-020-01314-6.
  12. Liu SV, Melstrom L, Yao K, et al. Neoadjuvant therapy for breast cancer. J Surg Oncol 2010; 101 (4): 283–91. doi: 10.21037/cco-20-123.
  13. Gomez HL, Doval DC, Chavez MA, et al. Efficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancer. J Clin Oncol 2008; 26 (18): 2999–3005.
  14. Khokher S, Qureshi MU, Chaudhry NA. Comparison of WHO and RECIST criteria for evaluation of clinical response to chemotherapy in patients with advanced breast cancer. Asian Pac J Cancer Prev 2012; 13 (7): 3213–18. doi: 10.7314/apjcp.2012.13.7.3213.
  15. Vinnik Y, Belevtsova Y, Sadchikova M. Prospects for increasing the efficiency of treatment of patients heaving of locally-distributed breast cancer. Eureka: Health Sciences 2020; (3): 6–12.
  16. Al-Thoubaity FK. Molecular classification of breast cancer: A retrospective cohort study. Ann Med Surg (Lond) 2020; 49: 44–8.
  17. Gadaleta E, Fourgoux P, Pirró S, et al. Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer. NPJ breast cancer 2020; 6 (1): 38. doi: 10.1038/s41523-020-00182-9.
  18. Turner KM, Yeo SK, Holm TM, et al. Heterogeneity within molecular subtypes of breast cancer. Am J Physiol Cell Physiol 2021; 321 (2): C343–C354. doi: 10.1152/ajpcell.00109.2021.
  19. Tong L, Yu X, Wang S, et al. Research progress on molecular subtyping and modern treatment of triple-negative breast cancer. Breast Cancer: Targets and Therapy 2023: 647–658.
  20. Huber KE, Carey LA, Wazer DE. Breast cancer molecular subtypes in patients with locally advanced disease: impact on prognosis, patterns of recurrence, and response to therapy. In: Seminars in radiation oncology 2009; 19 (4): 204–10.
  21. Dixon JM, Anderson TJ, Miller WR. Neoadjuvant endocrine therapy of breast cancer: a surgical perspective. Eur J Cancer 2002; 38 (17): 2214–21. doi: 10.1016/s0959-8049(02)00265-4.
  22. Munzone E, Colleoni M. Optimal management of luminal breast cancer: how much endocrine therapy is long enough? Ther Adv Med Oncol 2018; 10: 1758835918777437. doi: 10.1177/1758835918777437
  23. Li ZH, Hu PH, Tu JH, Yu NS. Luminal B breast cancer: patterns of recurrence and clinical outcome. Oncotarget 2016; 7 (40): 65024. doi: 10.18632/oncotarget.11344.
  24. Yeo B, Dowsett M. Neoadjuvant endocrine therapy: patient selection, treatment duration and surrogate endpoints. Breast 2015; 24: S78–S83. doi: 10.1016/j.breast.2015.07.019
  25. Madigan LI, Dinh P, Graham JD. Neoadjuvant endocrine therapy in locally advanced estrogen or progesterone receptor-positive breast cancer: determining the optimal endocrine agent and treatment duration in postmenopausal women—a literature review and proposed guidelines. Breast Cancer Res 2020; 22 (1): 1–13. doi: 10.1186/s13058-020-01314-6.
  26. Allevi G, Strina C, Andreis D, et al. Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer. Br J Cancer 2013; 108 (8), 1587-1592. doi: 10.1038/bjc.2013.151.
  27. Rusz O, Vörös A, Varga Z, et al. One-year neoadjuvant endocrine therapy in breast cancer. Pathol Oncol Res 2015; 21 (4): 977–84. doi:10.1007/s12253-015-9911-1.
  28. Łukasiewicz S, Czeczelewski M, Forma A, et al. Breast cancer-epidemiology, risk factors, classification, prognostic markers, and current treatment strategies-an updated review. Cancers (Basel) 2021; 13 (17): 4287. doi:10.3390/cancers13174287.
  29. Heneghan HM, Miller N, Kelly R, et al. Systemic miRNA-195 differentiates breast cancer from other malignancies and is a potential biomarker for detecting noninvasive and early stage disease. Oncologist 2010; 15 (7): 673–82. doi:10.1634/theoncologist.2010-0103.
  30. Place RF, Li LC, Pookot D, et al. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci USA 2008; 105 (5): 1608–13. doi:10.1073/pnas.0707594105.
  31. Riolo G, Cantara S, Marzocchi C, Ricci C. miRNA targets: from prediction tools to experimental validation. Methods Protoc 2020; 4(1): 1. doi:10.3390/mps4010001.
  32. Cantini L, Bertoli G, Cava C, et al. Identification of microRNA clusters cooperatively acting on epithelial to mesenchymal transition in triple negative breast cancer. Nucleic Acids Res 2019; 47 (5): 2205–15. doi:10.1093/nar/gkz016.
  33. Glinge C, Clauss S, Boddum K, et al. Stability of circulating blood-based micrornas – pre-analytic methodological considerations. PLoS One 2017; 12 (2): e0167969. doi:10.1371/journal.pone.0167969.
  34. Bahmanpour Z, Sheervalilou R, Choupani J, et al. A new insight on serum microRNA expression as novel biomarkers in breast cancer patients. J Cell Physiol 2019; 234 (11): 19199–211. doi:10.1002/jcp.28656.
  35. Agbu P, Carthew RW. MicroRNA-mediated regulation of glucose and lipid metabolism. Nat Rev Mol Cell Biol 2021; 22(6): 425–38. doi:10.1038/s41580-021-00354-w.
  36. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75 (5): 843–54. doi:10.1016/0092-8674(93)90529-y.
  37. Lowery AJ, Miller N, Devaney A, et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res 2009; 11(3): R27. doi:10.1186/bcr2257.
  38. Treeck O, Haerteis S, Ortmann O. Non-coding RNAs modulating estrogen signaling and response to endocrine therapy in breast cancer. Cancers (Basel) 2023; 15 (6): 1632. doi:10.3390/cancers15061632.
  39. Muluhngwi P, Klinge CM. Roles for miRNAs in endocrine resistance in breast cancer. Endocr Relat Cancer 2015; 22 (5): R279–R300. doi:10.1530/ERC-15-0355.
  40. Palmieri C, Cleator S, Kilburn LS, et al. NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer. Breast Cancer Res Treat 2014; 148 (3): 581–90. doi:10.1007/s10549-014-3183-4.
  41. Zhang W, Wu M, Chong QY, et al. Loss of estrogen-regulated MIR135A1 at 3p21.1 promotes tamoxifen resistance in breast cancer. Cancer Res 2018; 78 (17): 4915–28. doi: 1158/0008-5472.CAN-18-0069.
  42. Bergamaschi A, Katzenellenbogen BS. Tamoxifen downregulation of miR-451 increases 14-3-3ζ and promotes breast cancer cell survival and endocrine resistance. Oncogene 2012; 31 (1): 39–47. doi:10.1038/onc.2011.223.
  43. Petrović N, Nakashidze I, Nedeljković M. Breast cancer response to therapy: can microRNAs lead the way? J Mammary Gland Biol Neoplasia 2021; 26 (2): 157–78. doi:10.1007/s10911-021-09478-3.
  44. Hoppe R, Fan P, Büttner F, et al. Profiles of miRNAs matched to biology in aromatase inhibitor resistant breast cancer. Oncotarget 2016; 7 (44): 71235. doi: 10.18632/oncotarget.12103.
  45. Ouyang YX, Feng J, Wang Z, et al. miR-221/222 sponge abrogates tamoxifen resistance in ER-positive breast cancer cells through restoring the expression of ERα. Molecular Biomedicine 2021; (1): 20. doi:10.1186/s43556-021-00045-0.
  46. Rao X, Di Leva G, Li M, et al. MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways. Oncogene 2011; 30 (9): 1082–97. doi:10.1038/onc.2010.487.
  47. Muluhngwi P, Klinge CM. Identification of miRNAs as biomarkers for acquired endocrine resistance in breast cancer. Mol Cell Endocrinol 2017; 456: 76–86. doi:10.1016/j.mce.2017.02.004.
  48. Pridko O, Borikun T, Rossylna O, Rusyn AV. Association of miRNA expression pattern with outcome of letrozole therapy in breast cancer patients. Exp Oncol 2023; 45 (2): 180–6. doi:
  49. Pridko O, Borikun T, Rossylna O, et al. Expression pattern of miR-125b-2,-155,-221, and-320a is associated with response of breast cancer patients to tamoxifen. Exp Oncol 2022; и(4): 295–9. doi:
  50. Kudela E, Samec M, Koklesova L, et al. miRNA expression profiles in luminal a breast cancer-implications in biology, prognosis, and prediction of response to hormonal treatment. Int J Mol Sci 2020; 21 (20): 7691. doi:10.3390/ijms21207691.
  51. Liu X, Papukashvili D, Wang Z, et al. Potential utility of miRNAs for liquid biopsy in breast cancer. Front Oncol 2022; 12: 940314. doi:10.3389/fonc.2022.940314.
  52. Wei Y, Lai X, Yu S, et al. Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells. Breast Cancer Res Treat 2014; 147 (2): 423–31. doi:10.1007/s10549-014-3037-0.
  53. Amiruddin A, Massi MN, Islam AA, et al. microRNA-221 and tamoxifen resistance in luminal-subtype breast cancer patients: A case-control study. Ann Med Surg (Lond) 2021; 73: 103092. doi:10.1016/j.amsu.2021.103092.
  54. Di Cosimo S, Appierto V, Pizzamiglio S, et al. Plasma miRNA levels for predicting therapeutic response to neoadjuvant treatment in HER2-positive breast cancer: results from the NeoALTTO trial. Clin Cancer Res 2019; 25 (13): 3887–95. doi:10.1158/1078-0432.CCR-18-2507.

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