Alina Oana Rusu-Moldovan, Daniela Luminiu021ba Zob, Adrian Vasile Comanici, Maria Mihaela Comanici, Dan Mihu
Volume6-Issue1
Dates: Received: 2025-01-01 | Accepted: 2025-01-22 | Published: 2025-01-24
Pages: 056-069
Abstract
Breast cancer clinically represents a heterogeneous disease. Over decades, the integration of prognostic and predictive markers in treatment decisions has led to a more individualized and optimized therapy. Prognosis describes the risk of disease recurrence and disease-related death after diagnosis without the influence of therapy and prediction illustrates the probability of efficacy or response of a specific therapeutic measure.
The present study evaluated the clinical significance of Ki-67 index, ER, PGR, cerb-2 and Her2 receptors as prognostic markers and predictors of recurrence in different molecular subtypes of breast cancer. We analyzed the relationship of these receptors with different clinicopathological factors.
We have processed samples from 130 patients hospitalized in the Surgery Department III of the Bucharest Institute of Oncology. Biological samples have been taken by breast biopsy punctures or by excision of the tumors and analyzed them histopathologically and immunohistochemically.
Improved understanding of breast cancer biology and genetics together with the utilization of classical biomarkers and the identification of new markers or profiles is increasingly defining the clinical decisions are to be made to minimize overtreatment, undertreatment, and incorrect treatment.
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DOI: 10.37871/jbres2056
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© 2025 Rusu-Moldovan AO, et al. Distributed under Creative Commons CC-BY 4.0
How to cite this article
Rusu-Moldovan AO, Zob DL, Comanici AV, Comanici MM, Mihu D. Comparative Study of Biomarkers Dependent on Biological, Molecular Factors and Their Clinical Signifi cance in Breast Cancer Treatment. J Biomed Res Environ Sci. 2025 Jan 24; 6(1): 056-069. doi: 10.37871/jbres2056, Article ID: JBRES2056, Available at: https://www.jelsciences.com/articles/jbres2056.pdf
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References
- Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr; American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007 Nov 20;25(33):5287-312. doi: 10.1200/JCO.2007.14.2364. Epub 2007 Oct 22. PMID: 17954709.
- Dickson RB, Lippman ME. Autocrine and paracrine growth factors in the normal and neoplastic breast. In: Harris JR, Lippman ME, Morrow M. eds. Philadelphia; Lippincott Williams &Wilkins. 2000. 303.
- Pakkiri P, Lakhani SR, Smart CE. Current and future approach to the pathologist's assessment for targeted therapy in breast cancer. Pathology. 2009 Jan;41(1):89-99. doi: 10.1080/00313020802563551. PMID: 19089744.
- Masood S. Prognostic/predictive factors in breast cancer. Clin Lab Med. 2005 Dec;25(4):809-25, viii. doi: 10.1016/j.cll.2005.08.012. PMID: 16308094.
- Debies MT, Welch DR. Genetic basis of human breast cancer metastasis. J Mammary Gland Biol Neoplasia. 2001 Oct;6(4):441-51. doi: 10.1023/a:1014739131690. PMID: 12013533.
- de Snoo F, Bender R, Glas A, Rutgers E. Gene expression profiling: decoding breast cancer. Surg Oncol. 2009 Dec;18(4):366-78. doi: 10.1016/j.suronc.2009.07.005. PMID: 19879448.
- Kuderer NM, Lyman GH. Gene expression profile assays as predictors of distant recurrence-free survival in early-stage breast cancer. Cancer Invest. 2009 Nov;27(9):885-90. doi: 10.3109/07357900903275142. PMID: 19832034; PMCID: PMC3523732.
- Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0. PMID: 15894097.
- Taneja P, Maglic D, Kai F, Zhu S, Kendig RD, Fry EA, Inoue K. Classical and Novel Prognostic Markers for Breast Cancer and their Clinical Significance. Clin Med Insights Oncol. 2010 Apr 20;4:15-34. doi: 10.4137/cmo.s4773. PMID: 20567632; PMCID: PMC2883240.
- Nicolini A, Ferrari P, Duffy MJ. Prognostic and predictive biomarkers in breast cancer: Past, present and future. Semin Cancer Biol. 2018 Oct;52(Pt 1):56-73. doi: 10.1016/j.semcancer.2017.08.010. Epub 2017 Sep 4. PMID: 28882552.
- Schoppmann SF, Bayer G, Aumayr K, Taucher S, Geleff S, Rudas M, Kubista E, Hausmaninger H, Samonigg H, Gnant M, Jakesz R, Horvat R; Austrian Breast and Colorectal Cancer Study Group. Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer. Ann Surg. 2004 Aug;240(2):306-12. doi: 10.1097/01.sla.0000133355.48672.22. PMID: 15273556; PMCID: PMC1356408.
- Ferguson NL, Bell J, Heidel R, Lee S, Vanmeter S, Duncan L, Munsey B, Panella T, Orucevic A. Prognostic value of breast cancer subtypes, Ki-67 proliferation index, age, and pathologic tumor characteristics on breast cancer survival in Caucasian women. Breast J. 2013 Jan-Feb;19(1):22-30. doi: 10.1111/tbj.12059. Epub 2012 Dec 13. PMID: 23240985.
- von Minckwitz G, Untch M, Nüesch E, Loibl S, Kaufmann M, Kümmel S, Fasching PA, Eiermann W, Blohmer JU, Costa SD, Mehta K, Hilfrich J, Jackisch C, Gerber B, du Bois A, Huober J, Hanusch C, Konecny G, Fett W, Stickeler E, Harbeck N, Müller V, Jüni P. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat. 2011 Jan;125(1):145-56. doi: 10.1007/s10549-010-1228-x. Epub 2010 Nov 3. PMID: 21042932.
- EBCTCG Esobo: Highlights from the early breast cancer trialist collaborative group (EBCTCG) 2005-2006 worldwide overview. Breast Cancer Res Treat. 2009.
- Rakha EA, Chmielik E, Schmitt FC, Tan PH, Quinn CM, Gallagy G. Assessment of Predictive Biomarkers in Breast Cancer: Challenges and Updates. Pathobiology. 2022;89(5):263-277. doi: 10.1159/000525092. Epub 2022 Jun 21. PMID: 35728576.
- Dowsett M, Dunbier AK. Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res. 2008 Dec 15;14(24):8019-26. doi: 10.1158/1078-0432.CCR-08-0974. PMID: 19088018.
- Nicolini A, Ferrari P, Duffy MJ. Prognostic and predictive biomarkers in breast cancer: Past, present and future. Semin Cancer Biol. 2018 Oct;52(Pt 1):56-73. doi: 10.1016/j.semcancer.2017.08.010. Epub 2017 Sep 4. PMID: 28882552.
- Wu JR, Zhao Y, Zhou XP, Qin X. Estrogen receptor 1 and progesterone receptor are distinct biomarkers and prognostic factors in estrogen receptor-positive breast cancer: Evidence from a bioinformatic analysis. Biomed Pharmacother. 2020 Jan;121:109647. doi: 10.1016/j.biopha.2019.109647. Epub 2019 Nov 13. PMID: 31733575.
- Li CJ, Chen HM, Lai JC. Diagnostic, Prognostic, and Predictive Biomarkers in Breast Cancer. J Oncol. 2020 Mar 7;2020:1835691. doi: 10.1155/2020/1835691. PMID: 32256579; PMCID: PMC7091542.
- Tarighati E, Keivan H, Mahani H. A review of prognostic and predictive biomarkers in breast cancer. Clin Exp Med. 2023 Feb;23(1):1-16. doi: 10.1007/s10238-021-00781-1. Epub 2022 Jan 15. PMID: 35031885.
- Middleton LP, Chen V, Perkins GH, Pinn V, Page D. Histopathology of breast cancer among African-American women. Cancer. 2003 Jan 1;97(1 Suppl):253-7. doi: 10.1002/cncr.11021. PMID: 12491489.
- Soliman NA, Yussif SM. Ki-67 as a prognostic marker according to breast cancer molecular subtype. Cancer Biol Med. 2016 Dec;13(4):496-504. doi: 10.20892/j.issn.2095-3941.2016.0066. PMID: 28154782; PMCID: PMC5250608.
- Fernandopulle SM, Cher-Siangang P, Tan PH. Breast carcinoma in women 35 years and younger: a pathological study. Pathology. 2006 Jun;38(3):219-22. doi: 10.1080/00313020600699268. PMID: 16753742.
- Singhai R, Patil V, Patil A. Status of HER-2/neu receptors and Ki-67 in breast cancer of Indian women. Int J Appl Basic Med Res. 2011 Jan;1(1):15-9. doi: 10.4103/2229-516X.81974. PMID: 23776766; PMCID: PMC3657947.
- Badowska-Kozakiewicz AM, Patera J, Sobol M, Przybylski J. The role of oestrogen and progesterone receptors in breast cancer - immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women. Contemp Oncol (Pozn). 2015;19(3):220-5. doi: 10.5114/wo.2015.51826. Epub 2015 May 28. PMID: 26557763; PMCID: PMC4631285.
- Potemski P, Pluciennik E, Bednarek AK, Kusinska R, Kubiak R, Kordek R. Evaluation of oestrogen receptor expression in breast cancer by quantification of mRNA. Histopathology. 2007 Dec;51(6):829-36. doi: 10.1111/j.1365-2559.2007.02886.x. PMID: 18042072.
- Kollias J, Elston CW, Ellis IO, Robertson JF, Blamey RW. Early-onset breast cancer--histopathological and prognostic considerations. Br J Cancer. 1997;75(9):1318-23. doi: 10.1038/bjc.1997.223. PMID: 9155052; PMCID: PMC2228226.
- Witters L, Engle L, Lipton A. Restoration of estrogen responsiveness by blocking the HER-2/neu pathway. Oncol Rep. 2002 Nov-Dec;9(6):1163-6. PMID: 12375012.
- Liu G, Wang L, Ji L, He D, Zeng L, Zhuo G, Zhang Q, Wang D, Pan Y. Identifying prognostic markers in spatially heterogeneous breast cancer microenvironment. J Transl Med. 2023 Aug 29;21(1):580. doi: 10.1186/s12967-023-04395-x. PMID: 37644433; PMCID: PMC10463390.
- Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol. 2003 May 15;21(10):1973-9. doi: 10.1200/JCO.2003.09.099. PMID: 12743151.
- Bougie O, Weberpals JI. Clinical Considerations of BRCA1- and BRCA2-Mutation Carriers: A Review. Int J Surg Oncol. 2011;2011:374012. doi: 10.1155/2011/374012. Epub 2011 Aug 8. PMID: 22312502; PMCID: PMC3263675.
- Lee EH, Park SK, Park B, Kim SW, Lee MH, Ahn SH, Son BH, Yoo KY, Kang D; KOHBRA Research Group; Korean Breast Cancer Society. Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and meta-analysis. Breast Cancer Res Treat. 2010 Jul;122(1):11-25. doi: 10.1007/s10549-010-0859-2. Epub 2010 Apr 8. PMID: 20376556.
- Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M, Dent R, Lubinski J, Narod S. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010 Jan 20;28(3):375-9. doi: 10.1200/JCO.2008.20.7019. Epub 2009 Dec 14. PMID: 20008645.
- Taneja P, Maglic D, Kai F, Zhu S, Kendig RD, Fry EA, Inoue K. Classical and Novel Prognostic Markers for Breast Cancer and their Clinical Significance. Clin Med Insights Oncol. 2010 Apr 20;4:15-34. doi: 10.4137/cmo.s4773. PMID: 20567632; PMCID: PMC2883240.
- Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123-34. doi: 10.1056/NEJMoa0900212. Epub 2009 Jun 24. PMID: 19553641.
- Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):235-44. doi: 10.1016/S0140-6736(10)60892-6. Epub 2010 Jul 6. PMID: 20609467.