One of the primary concerns for women in good health is breast cancer. The most typical hazardous growth is this one. It spreads easily, and the clinical conditions are terrible. Bosom illness is the second‐most common type of malignant tumor that regularly causes women to pass away in the U.S. bosom malignant growth is the most well‐known disease among women worldwide, with 2.1 million cases reported in 2018 and more than 620,000 fatalities per year. Natural components are viewed as promising alternatives for the development of novel anti‐tumor drugs. Curcumin, also termed diferuloylmethane, is a yellow pigment made by the turmeric plant, Curcuma longa Linn. It is the curcuminoid and polyphenol present in the plant’s root that is most abundant. The antioxidant and anti‐inflammatory qualities of curcumin have been demonstrated, and it is frequently utilized in traditional medicine and cuisine. Due to its sophisticated pharmacological capabilities of chemoprevention and anticancer effects, curcumin, the main component of turmeric, has been linked to the treatment of breast cancer. The morbidity or mortality of the disease have not been significantly decreased by current breast cancer treatment options such as surgery, radiation, adjuvant chemotherapy, or hormone therapy. The expansion, estrogen receptor (trauma center), and human epidermal development factor receptor 2 (HER2) pathways are all involved in the activity of curcumin in illness. In breast cancer cells, curcumin is also known to regulate microRNA, cell stage-related characteristics, and apoptosis. This study reviews recent research on the atomic targets and anticancer effects of curcumin in breast cancer.

1. Zoi V, Galani V, Lianos GD, et al. The role of curcumin in cancer treatment. Biomedicines 2021; 9(9): 1086. doi: 10.3390/biomedicines9091086

2. Corti C, Giachetti PPMB, Eggermont AMM, et al. Therapeutic vaccines for breast cancer: Has the time finally come? European Journal of Cancer 2022; 160: 150–174. doi: 10.1016/j.ejca.2021.10.027

3. Sharma RA, Gescher AJ, Steward WP. Curcumin: The story so far. European Journal of Cancer 2005; 41(13): 1955–1968. doi: 10.1016/j.ejca.2005.05.009

4. Shaikh S, Shaikh J, Naba YS, et al. Curcumin: Reclaiming the lost ground against cancer resistance. Cancer Drug Resistance 2021; 4(2): 298–320. doi: 10.20517/cdr.2020.92

5. Pavan A, da Silva CDB, Jornada DH, et al. Unraveling the anticancer effect of curcumin and resveratrol. Nutrients 2016; 8(11): 628. doi: 10.3390/nu8110628

6. Panjaa A, Pandey NK, Singha SK, et al. Quality by design—A tool for quality management. Think India 2019; 22(17): 3437–3451.

7. Kumar B, Malik AH, Sharma P, et al. Validated reversed-phase high-performance liquid chromatography method for simultaneous estimation of curcumin and duloxetine hydrochloride in tablet and self-nanoemulsifying drug delivery systems. Journal of Pharmacy Research 2017; 11(9): 1166–1177.

8. Garg V, Kaur P, Gulati M, et al. Coadministration of polypeptide-k and curcumin through solid self-nanoemulsifying drug delivery system for better therapeutic effect against diabetes mellitus: Formulation, optimization, biopharmaceutical characterization, and pharmacodynamic assessment. Assay and Drug Development Technologies 2019; 17(4): 201–221. doi: 10.1089/adt.2018.902

9. Jyoti J, Anandhakrishnan NK, Singh SK, et al. A three-pronged formulation approach to improve oral bioavailability and therapeutic efficacy of two lipophilic drugs with gastric lability. Drug Delivery and Translational Research 2019; 9(4): 848–865. doi: 10.1007/s13346-019-00635-0

10. Kaur M, Singh A, Kumar B, et al. Protective effect of co-administration of curcumin and sildenafil in alcohol induced neuropathy in rats. European Journal of Pharmacology 2017; 805: 58–66. doi: 10.1016/j.ejphar.2017.03.012

11. Khursheed R, Singh SK, Kumar B, et al. Self-nanoemulsifying composition containing curcumin, quercetin, Ganoderma lucidum extract powder and probiotics for effective treatment of type 2 diabetes mellitus in streptozotocin induced rats. International Journal of Pharmaceutics 2022; 612: 121306. doi: 10.1016/j.ijpharm.2021.121306

12. Kumar B, Garg V, Singh S, et al. Investigation and optimization of formulation parameters for selfnanoemulsifying delivery system of two lipophilic and gastrointestinal labile drugs using box-behnken design. Asian Journal of Pharmaceutical and Clinical Research 2018; 11(14): 12. doi: 10.22159/ajpcr.2018.v11s2.28585

13. Kumar B, Garg V, Singh S, et al. Impact of spray drying over conventional surface adsorption technique for improvement in micromeritic and biopharmaceutical characteristics of self-nanoemulsifying powder loaded with two lipophilic as well as gastrointestinal labile drugs. Powder Technology 2018; 326: 425–442. doi: 10.1016/j.powtec.2017.12.005

14. Kumar B, Singh SK, Prakash T, et al. Pharmacokinetic and pharmacodynamic evaluation of Solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcumin and duloxetine in attenuation of neuropathic pain in rats. Neurological Sciences 2020; 42(5): 1785–1797. doi: 10.1007/s10072-020-04628-7

15. Choudhuri T, Pal S, Agwarwal ML, et al. Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Letters 2002; 512(1–3): 334–340. doi: 10.1016/S0014-5793(02)02292-5

16. Kelsey JL, Berkowitz GS. Breast cancer epidemiology. Cancer Research 1988; 48(20): 5615–5623.

17. Rojas K, Stuckey A. Breast cancer epidemiology and risk factors. Clinical Obstetrics and Gynecology 2016; 59(4): 651–672.

18. Barlow WE, Lehman CD, Zheng Y, et al. Performance of diagnostic mammography for women with signs or symptoms of breast cancer. Journal of the National Cancer Institute 2002; 94(15): 1151–1159. doi: 10.1093/jnci/94.15.1151

19. Akram M, Iqbal M, Daniyal M, et al. Awareness and current knowledge of breast cancer. Biological research 2017; 50(1): 1–23.

20. Hulka BS, Stark AT. Breast cancer: Cause and prevention. The Lancet 1995; 346(8979): 883–887. doi: 10.1016/S0140-6736(95)92713-1

21. Qiao A, Gu F, Guo X, et al. Breast cancer-associated fibroblasts: Their roles in tumor initiation, progression and clinical applications. Frontiers of Medicine 2016; 10(1): 33–40. doi: 10.1007/s11684-016-0431-5

22. Januškevičienė I, Petrikaitė V. Heterogeneity of breast cancer: The importance of interaction between different tumor cell populations. Life Sciences 2019; 239: 117009. doi: 10.1016/j.lfs.2019.117009

23. Soysal SD, Tzankov A, Muenst SE. Role of the tumor microenvironment in breast cancer. Pathobiology 2015; 82(3–4): 142–152. doi: /10.1159/000430499

24. Mittal S, Brown NJ, Holen I. The breast tumor microenvironment: Role in cancer development, progression and response to therapy. Expert Review of Molecular Diagnostics 2018; 18(3): 227–243. doi: 10.1080/14737159.2018.1439382

25. Yip CH. Palliation and breast cancer. Journal of Surgical Oncology 2017; 115(5): 538–543. doi: 10.1002/jso.24560

26. Sharma GN, Daveet R, Sanadyaal J, et al. Various types and management of breast cancer: An overview. Journal of Advanced Pharmaceutical Technology & Research 2010; 1(2): 109–126.

27. McDonald ES, Clark AS, Tchou J, et al. Clinical diagnosis and management of breast cancer. Journal of Nuclear Medicine 2016; 57(Supplement 1): 9S–16S. doi: 10.2967/jnumed.115.157834

28. Abbas SH, Abdulridha MK, Najeb AA. Potential benefit of curcumin adjuvant therapy to the standard helicobacter pylori eradication therapy in patients with peptic ulcer disease. Asian Journal of Pharmaceutical and Clinical Research 2017; 10(5): 313–317. doi: 10.22159/ajpcr.2017.v10i5.17462

29. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Scientific opinion on the re‐evaluation of curcumin (E 100) as a food additive. EFSA Journal 2010; 8(9): 1679. doi: 10.2903/j.efsa.2010.1679

30. Aggarwal BB, Deb L, Prasad S. Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular responses. Molecules 2015; 20(1): 185–205. doi: 10.3390/molecules20010185

31. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. The International Journal of Biochemistry & Cell Biologyry 2009; 41(1): 40–59. doi: 10.1016/j.biocel.2008.06.010

32. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Research 2003; 23(1A): 363–398.

33. Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: The Indian solid gold. In: Aggarwal BB, Surh YJ, Shishodia S (editors). The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. Springer; 2007. Volume 595. pp. 1–75.

34. Aggarwal BB, Yuan W, Li S, Gupta SC. Curcumin‐free turmeric exhibits anti‐inflammatory and anticancer activities: Identification of novel components of turmeric. Molecular Nutrition & Food Research 2013; 57(9): 1529–1542. doi: 10.1002/mnfr.201200838

35. Ahmad M. Protective effects of curcumin against lithium-pilocarpine induced status epilepticus, cognitive dysfunction and oxidative stress in young rats. Saudi Journal of Biological Sciences 2013; 20(2): 155–162. doi: 10.1016/j.sjbs.2013.01.002

36. Ahmadi N, Hosseini MJ, Rostamizadeh K, Anoush M. Investigation of therapeutic effect of curcumin α and β glucoside anomers against Alzheimer’s disease by the nose to brain drug delivery. Brain Research 2021; 1766: 147517. doi: 10.1016/j.brainres.2021.147517

37. Ahmed T, Enam S, Gilani AH. Curcuminoids enhance memory in an amyloid-infused rat model of Alzheimer’s disease. Neuroscience 2010; 169(3): 1296–1306. doi: 10.1016/j.neuroscience.2010.05.078

38. Arablou T, Kolahdouz-Mohammadi R. Curcumin and endometriosis: Review on potential roles and molecular mechanisms. Biomedicine & Pharmacotherapy 2018; 97: 91–97. doi: 10.1016/j.biopha.2017.10.119

39. Banafshe HR, Hamidi GA, Noureddini M, et al. Effect of curcumin on diabetic peripheral neuropathic pain: Possible involvement of opioid system. European Journal of Pharmacology 2014; 723: 202–206. doi: 10.1016/j.ejphar.2013.11.033

40. Carroll CE, Ellersieck MR, Hyder SM. Curcumin inhibits MPA-induced secretion of VEGF from T47-D human breast cancer cells. Menopause 2008; 15(3): 570–574. doi: 10.1097/gme.0b013e31814fae5d

41. Ceyhan D, Kocman AE, Yildirim E, et al. Comparison of the effects of curcumin, tramadol and surgical treatments on neuropathic pain induced by chronic constriction injury in rats. Turkish Neurosurgery 2018; 28(2): 288–295. doi: 10.5137/1019-5149.jtn.19824-17.0

42. Zahedipour F, Hosseini SA, Sathyapalanal T, et al. Potential effects of curcumin in the treatment of COVID‐19 infection. Phytotherapy Research 2020; 34(11): 2911–2920. doi: 10.1002/ptr.6738

43. Feng R, Song Z, Zhai G. Preparation and in vivo pharmacokinetics of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles. International Journal of Nanomedicine 2012; 7: 4089–4098. doi: 10.2147/IJN.S33607

44. Gouya G, Aschauer S, Weisshaar S, Storka A. Human pharmacokinetics of high dose oral curcumin and its effect on heme oxygenase-1 expression in healthy male subjects. BioMed Research International 2014; 458592. doi: 10.1155/2014/458592

45. Shoba G, Joy D, Joseph T, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta medica 1998; 64(04): 353–356. doi: 10.1055/s-2006-957450

46. Storka A, Vcelar B, Klickovic U, et al. Safety, tolerability and pharmacokinetics of liposomal curcumin (Lipocurc™) in healthy humans. International Journal of Clinical Pharmacology and Therapeutics 2015; 53(1): 54–65. doi: 10.5414/CP202076

47. Wang L, Li W, Cheng D, et al. Pharmacokinetics and pharmacodynamics of three oral formulations of curcumin in rats. Journal of Pharmacokinetics and Pharmacodynamics 2020; 47(2): 131–144. doi: 10.1007/s10928-020-09675-3

48. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: Problems and promises. Molecular Pharmaceutics 2007; 4(6): 807–818. doi: 10.1021/mp700113r

49. Anitha A, Deepagan VG, Divya Rani VV, et al. Preparation, characterization, in vitro drug release and biological studies of curcumin loaded dextran sulphate—Chitosan nanoparticles. Carbohydrate Polymers 2011; 84(3): 1158–1164. doi: 10.1016/j.carbpol.2011.01.005

50. Chiu SS, Lui E, Majeed M, et al. Differential distribution of intravenous curcumin formulations in the rat brain. Anticancer Research 2011; 31(3): 907–911.

51. Daugherty DJ, Marquez A, Calcutt NA, Schubert D. A novel curcumin derivative for the treatment of diabetic neuropathy. Neuropharmacology 2018; 129: 26–35. doi: 10.1016/j.neuropharm.2017.11.007

52. Díaz-Triste NE, González-García MP, Jiménez-Andrade JM, et al. Pharmacological evidence for the participation of NO–cGMP–KATP pathway in the gastric protective effect of curcumin against indomethacin-induced gastric injury in the rat. European Journal of Pharmacology 2014; 730: 102–106. doi: 10.1016/j.ejphar.2014.02.030

53. Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutrition and Cancer 2010; 62(7): 919–930. doi: 10.1080/01635581.2010.509835

54. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: From kitchen to clinic. Biochemical Pharmacology 2008; 75(4): 787–809. doi: 10.1016/j.bcp.2007.08.016

55. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: Lessons learned from clinical trials. The AAPS Journal 2013; 15(1): 195–218. doi: 10.1208/s12248-012-9432-8

56. Han Y, Sun HJ, Tong Y, et al. Curcumin attenuates migration of vascular smooth muscle cells via inhibiting NFκB-mediated NLRP3 expression in spontaneously hypertensive rats. The Journal of Nutritional Biochemistry 2019; 72: 108212. doi: 10.1016/j.jnutbio.2019.07.003

57. Han YK, Lee SH, Jeong HJ, et al. Analgesic effects of intrathecal curcumin in the rat formalin test. The Korean Journal of Pain 2012; 25(1): 1–6. doi: 10.3344/kjp.2012.25.1.1

58. He ZY, Shi CB, Wen H, et al. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Investigation 2011; 29(3): 208–213. doi: 10.3109/07357907.2010.550592

59. Hewlings SJ, Kalman DS. Curcumin: A review of its effects on human health. Foods 2017; 6(10): 92. doi: 10.3390/foods6100092

60. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Research 2001; 21(4B): 2895–2900.

61. Sohn SI, Priya A, Balasubramaniam B, et al. Biomedical applications and bioavailability of curcumin—An updated overview. Pharmaceutics 2021; 13(12): 2102. doi: 10.3390/pharmaceutics13122102

62. John PCl, Mews M, Moore R. Cyclin/Cdk complexes: Their involvement in cell cycle progression and mitotic division. Protoplasma 2001; 216(3–4): 119–142. doi: 10.1007/bf02673865

63. Villegas SL, Darb-Esfahani S, von Minckwitz G, et al. Expression of Cyclin D1 protein in residual tumor after neoadjuvant chemotherapy for breast cancer. Breast Cancer Research and Treatment 2018; 168(1): 179–187. doi: 10.1007/s10549-017-4581-1

64. Lamb R, Lehn S, Rogerson L, et al. Cell cycle regulators cyclin D1 and CDK4/6 have estrogen receptor-dependent divergent functions in breast cancer migration and stem cell-like activity. Cell Cycle 2013; 12(15): 2384–2394. doi: 10.4161/cc.25403

65. Peurala E, Koivunen P, Haapasaari KM, et al. The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer. Breast Cancer Research 2013; 15(1): 1–10. doi: 10.1186/bcr3376

66. Aggarwal BB, Banerjee S, Bharadwaj U, et al. RETRACTED: Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochemical Pharmacology 2007; 73(7): 1024–1032. doi: 10.1016/j.bcp.2006.12.010

67. Doostan I, Karakas C, Kohansal M, et al. Cytoplasmic cyclin E mediates resistance to aromatase inhibitors in breast cancer. Clinical Cancer Research 2017; 23(23): 7288–7300. doi: 10.1158/1078-0432.CCR-17-1544

68. Mazumder S, DuPree EL, AlmasanA. A dual role of cyclin E in cell proliferation and apotosis may provide a target for cancer therapy. Current Cancer Drug Targets 2004; 4(1): 65–75. doi: 10.2174/1568009043481669

69. Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance across 12 major cancer types. Nature 2013; 502(7471): 333–339. doi: 10.1038/nature12634

70. Muller PAJ, Vousden KH. Mutant p53 in cancer: New functions and therapeutic opportunities. Cancer Cell 2014; 25(3): 304–317. doi: 10.1016/j.ccr.2014.01.021

71. Fan H, Liang Y, Jiang B, et al. Curcumin inhibits intracellular fatty acid synthase and induces apoptosis in human breast cancer MDA-MB-231 cells. Oncology Reports 2016; 35(5): 2651–2656. doi: 10.3892/or.2016.4682

72. Adjei AA. Blocking oncogenic Ras signaling for cancer therapy. Journal of the National Cancer Institute 2001; 93(14): 1062–1074. doi: 10.1093/jnci/93.14.1062

73. Kim MS, Kang HJ, Moon A. Inhibition of invasion and induction of apoptosis by curcumin in H-ras-transformed MCF10A human breast epithelial cells. Archives of Pharmacal Research 2001; 24(4): 349–354. doi: 10.1007/BF02975105

74. Ono M, Higuchi T, Takeshima M, et al. Differential anti-tumor activities of curcumin against Ras-and Src-activated human adenocarcinoma cells. Biochemical and Biophysical Research Communications 2013; 436(2): 186–191. doi: 10.1016/j.bbrc.2013.05.071

75. Ettl T, Schwarz-Furlan S, Haubner F, et al. The PI3K/AKT/mTOR signalling pathway is active in salivary gland cancer and implies different functions and prognoses depending on cell localisation. Oral oncology 2012; 48(9): 822–830. doi: 10.1016/j.oraloncology.2012.02.021

76. Chen WC, Lai YA, Lin YC, et al. Curcumin suppresses doxorubicin-induced epithelial–mesenchymal transition via the inhibition of TGF-β and PI3K/AKT signaling pathways in triple-negative breast Cancer cells. Journal of Agricultural and Food Chemistry 2013; 61(48): 11817–11824. doi: 10.1021/jf404092f

77. Carnero A, Blanco-Aparicio C, Renner O, et al. The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Current Cancer Drug Targets 2008; 8(3): 187–198. doi: 10.2174/156800908784293659

78. Akkoç Y, Berrak O, Arısan ED, et al. Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl-2 through activation of autophagy in MCF-7 cells. Biomedicine & Pharmacotherapy 2015; 71: 161–171. doi: 10.1016/j.biopha.2015.02.029

79. Yu S, Shen G; Khor TO, et al. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Molecular Cancer Therapeutics 2008; 7(9): 2609–2620. doi: 10.1158/1535-7163.MCT-07-2400

80. Ma X, Zhao X, Yan W, et al. Tumor-infiltrating lymphocytes are associated with β-catenin overexpression in breast cancer. Cancer Biomarkers 2018; 21(3): 639–650. doi: 10.3233/CBM-170708

81. Roy A, Ansari SA, Das K, et al. Coagulation factor VIIa-mediated protease-activated receptor 2 activation leads to β-catenin accumulation via the AKT/GSK3β pathway and contributes to breast cancer progression. Journal of Biological Chemistry 2017; 292(33): 13688–13701. doi: 10.1074/jbc.M116.764670

82. Gao s, Ge A, Xu S, et al. PSAT1 is regulated by ATF4 and enhances cell proliferation via the GSK3β/β-catenin/cyclin D1 signaling pathway in ER-negative breast cancer. Journal of Experimental & Clinical Cancer Research 2017; 36(1): 1–13. doi: 10.1186/s13046-017-0648-4

83. Prasad CP, Rath G, Mathur S, et al. Potent growth suppressive activity of curcumin in human breast cancer cells: Modulation of Wnt/β-catenin signaling. Chemico-Biological Interactions 2009; 181(2): 263–271. doi: 10.1016/j.cbi.2009.06.012

84. Park YH. The nuclear factor-kappa B pathway and response to treatment in breast cancer. Pharmacogenomics 2017; 18(18): 1697–1709. doi: 10.2217/pgs-2017-0044

85. Shishodia S, Sethi G, Aggarwal BB. Curcumin: Getting back to the roots. Annals of the New York Academy of Sciences 2005; 1056(1): 206–217. doi: 10.1196/annals.1352.010

86. Shehzad A, Qureshi M, Anwar MN, Lee YS. Multifunctional curcumin mediate multitherapeutic effects. Concise Reviews & Hypotheses in Food Science 2017; 82(9): 2006–2015. doi: 10.1111/1750-3841.13793

87. Saberi-Karimian M, Katsiki N, Caraglia M, et al. Vascular endothelial growth factor: An important molecular target of curcumin. Critical Reviews in Food Science and Nutrition 2019; 59(2): 299–312. doi: 10.1080/10408398.2017.1366892

88. Chakraborty G, Jain S, Kale S, et al. Curcumin suppresses breast tumor angiogenesis by abrogating osteopontin-induced VEGF expression. Molecular Medicine Reports 2008; 1(5): 641–646. doi: 10.3892/mmr_00000005

89. Song X, Zhang M, Dai E, Luo Y. Molecular targets of curcumin in breast cancer. Molecular Medicine Reports 2019; 19(1): 23–29. doi: 10.3892/mmr.2018.9665

90. Berrak Ö, Akkoç Y, Arısan ED, et al. The inhibition of PI3K and NFκB promoted curcumin-induced cell cycle arrest at G2/M via altering polyamine metabolism in Bcl-2 overexpressing MCF-7 breast cancer cells. Biomedicine & Pharmacotherapy 2016; 77: 150–160. doi: 10.1016/j.biopha.2015.12.007

91. Poma P, Labbozzetta M, D’Alessandro N, Notarbartolo M. NF-κB is a potential molecular drug target in triple-negative breast cancers. Omics: A Journal of Integrative Biology 2017; 21(4): 225–231. doi: 10.1089/omi.2017.0020

92. Huang T, Chen Z, Fang L. Curcumin inhibits LPS-induced EMT through downregulation of NF-κB-Snail signaling in breast cancer cells. Oncology Reports 2013; 29(1): 117–124. doi: 10.3892/or.2012.2080

93. Norouzi S, Majeed M, Pirro M, et al. Curcumin as an adjunct therapy and microRNA modulator in breast cancer. Current pharmaceutical design 2018; 24(2): 171–177. doi: 10.2174/1381612824666171129203506

94. Chen J, Wang FL, Chen WD. Modulation of apoptosis-related cell signalling pathways by curcumin as a strategy to inhibit tumor progression. Molecular Biology Reports 2014; 41(7): 4583–4594. doi: 10.1007/s11033-014-3329-9

95. Lai HW, Chien SY, Kuo SJ, et al. The potential utility of curcumin in the treatment of HER-2-overexpressed breast cancer: An in vitro and in vivo comparison study with herceptin. Evidence-Based Complementary and Alternative Medicine 2012; 12: 486568. doi:10.1155/2012/486568

96. Wang X, Hang Y, Liu J, et al. Anticancer effect of curcumin inhibits cell growth through miR-21/PTEN/Akt pathway in breast cancer cell. Oncology Letters 2017; 13(6): 4825–4831. doi: 10.3892/ol.2017.6053

97. Saghatelyan T, Tananyan A, Janoyan N, et al. Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine 2020; 70: 153218. doi: 10.1016/j.phymed.2020.153218

98. Farghadani R, Naidu R. Curcumin: Modulator of key molecular signaling pathways in hormone-independent breast cancer. Cancers 2021; 13(14): 3427. doi: 10.3390/cancers13143427

99. Zhou Q, Ye M, Lu Y, et al. Curcumin improves the tumoricidal effect of mitomycin C by suppressing ABCG2 expression in stem cell-like breast cancer cells. PloS One 2015; 10(8): e0136694. doi: 10.1371/journal.pone.0136694

100. Wen C, Fu L, Huang J, et al. Curcumin reverses doxorubicin resistance via inhibition the efflux function of ABCB4 in doxorubicin‑resistant breast cancer cells. Molecular Medicine Reports 2019; 19(6): 5162–5168. doi: 10.3892/mmr.2019.10180

101. Calaf GM, Ponce-Cusi R, Carrión F. Curcumin and paclitaxel induce cell death in breast cancer cell lines. Oncology Reports 2018; 40(4): 2381–2388. doi: 10.3892/or.2018.6603

102. Vinod BS, Antony J, Nair HH, et al. Mechanistic evaluation of the signaling events regulating curcumin-mediated chemosensitization of breast cancer cells to 5-fluorouracil. Cell Death & Disease 2013; 4(2): e505. doi: 10.1038/cddis.2013.26

103. Farghadani R, Naidu R. Curcumin as an enhancer of therapeutic efficiency of chemotherapy drugs in breast cancer. International Journal of Molecular Sciences 2022; 23(4): 2144. doi: 10.3390/ijms23042144

104. Kumari M, Sharma N, Manchanda R, et al. PGMD/curcumin nanoparticles for the treatment of breast cancer. Scientific Reports 2021; 11(1): 3824. doi: 10.1038/s41598-021-81701-x

105. Honarvari B, Karimifard S, Akhtari N, et al. Folate-targeted curcumin-loaded niosomes for site-specific delivery in breast cancer treatment: In silico and in vitro study. Molecules 2022; 27(14): 4634. doi: 10.3390/molecules27144634

106. Ashkbar A, Rezaei F, Attari F, Ashkevarian S. Treatment of breast cancer in vivo by dual photodynamic and photothermal approaches with the aid of curcumin photosensitizer and magnetic nanoparticles. Scientific Reports 2020; 10(1): 21206. doi: 10.1038/s41598-020-78241-1

107. Ji P, Wang L, Chen Y, et al. Hyaluronic acid hydrophilic surface rehabilitating curcumin nanocrystals for targeted breast cancer treatment with prolonged biodistribution. Biomaterials Science 2020; 8(1): 462–472. doi: 10.1039/c9bm01605h

108. Ghosh S, Dutta S, Sarkar A, et al. Targeted delivery of curcumin in breast cancer cells via hyaluronic acid modified mesoporous silica nanoparticle to enhance anticancer efficiency. Colloids and Surfaces B: Biointerfaces 2021; 197: 111404. doi: 10.1016/j.colsurfb.2020.111404

109. Mohebian Z, Babazadeh M, Zarghami N, Mousazadeh H. Anticancer efficiency of curcumin-loaded mesoporous silica nanoparticles/nanofiber composites for potential postsurgical breast cancer treatment. Journal of Drug Delivery Science and Technology 2021; 61: 102170. doi: 10.1016/j.jddst.2020.102170

110. Minafra L, Porcino N, BravatàV, et al. Radiosensitizing effect of curcumin-loaded lipid nanoparticles in breast cancer cells. Scientific Reports 2019; 9(1): 11134. doi: 10.1038/s41598-019-47553-2

111. Wang L, Wang C, Tao Z, et al. Curcumin derivative WZ35 inhibits tumor cell growth via ROS-YAP-JNK signaling pathway in breast cancer. Journal of Experimental & Clinical Cancer Research 2019; 38(1): 460. doi: 10.1186/s13046-019-1424-4

112. Hortobagyi GN. Treatment of breast cancer. New England Journal of Medicine 1998; 339(14): 974–984. doi: 10.1056/NEJM199810013391407

113. Richie RC, Swanson JO. Breast cancer: A review of the literature. Journal of Insurance Medicine 2003； 35(2): 85–101.

114. Diaz LA, Bardelli A. Liquid biopsies: Genotyping circulating tumor DNA. Journal of Clinical Oncology 2014; 32(6): 579–586. doi: 10.1200/JCO.2012.45.2011

115. Pang B, Zhu Y, Ni J, et al. Extracellular vesicles: The next generation of biomarkers for liquid biopsy-based prostate cancer diagnosis. Theranostics 2020; 10(5): 2309–2326. doi: 10.7150/thno.39486

116. Best MG, Sol N, Kooi I, et al. RNA-Seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics. Cancer Cell 2015; 28(5): 666–676. doi: 10.1016/j.ccell.2015.09.018

117. Yoshioka Y, Kosaka N, Konishi Y, et al. Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen. Nature Communications 2014; 5(1): 3591. doi: 10.1038/ncomms4591

118. Lee Y, Ni J, Beretov J, et al. Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis. Molecular Cancer 2023; 22(1): 33. doi: 10.1186/s12943-023-01741-x

119. Rappuoli R, Pizza M, del Giudice G, de Gregorio E. Vaccines, new opportunities for a new society. Proceedings of the National Academy of Sciences 2014; 111(34): 12288–12293. doi: 10.1073/pnas.1402981111

120. Igarashi Y, Sasada T. Cancer vaccines: Toward the next breakthrough in cancer immunotherapy. Journal of Immunology Research 2020. doi: 10.1155/2020/5825401

121. Smith RT. Immune Surveillance. Academic Press; 2012.

122. Bitton RJ. Cancer vaccines: A critical review on clinical impact. Current Opinion in Molecular Therapeutics 2004; 6(1): 17–26.

123. Starling S. Immune editing shapes the cancer landscape. Nature Reviews Immunology 2017; 17(12): 729–729.

124. Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: From T cell basic science to clinical practice. Nature Reviews Immunology 2020; 20(11): 651–668. doi: 10.1038/s41577-020-0306-5

125. McCarthy EF. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. The Iowa orthopaedic Journal 2006; 26: 154–158.

126. Hegde PS, Chen DS. Top 10 challenges in cancer immunotherapy. Immunity 2020; 52(1): 17–35. doi: 10.1016/j.immuni.2019.12.011

127. Giordano A, Tommonaro G. Curcumin and cancer. Nutrients 2019; 11(10): 2376. doi: 10.3390/nu11102376

128. Ombredane AS, Silva VRP, Andrade LR, et al. In vivo efficacy and toxicity of curcumin nanoparticles in breast cancer treatment: A systematic review. Frontiers in Oncology 2021; 11: 612903. doi: 10.3389/fonc.2021.612903

129. Arzani H, Adabi M, Mosafer J, et al. Preparation of curcumin-loaded PLGA nanoparticles and investigation of its cytotoxicity effects on human glioblastoma U87MG cells. Biointerface Research in Applied Chemistry 2019; 9(5): 4225–4231. doi: 10.33263/BRIAC95.225231

130. El-Hak HNG, Mobarak YM. The ameliorative impacts of curcumin on copper oxychloride-induced hepatotoxicity in rats. The Journal of Basic and Applied Zoology 2018; 79(44): 52. doi: 10.1186/s41936-018-0059-x

131. Jiang T, Zhi XL, Zhang YH. Inhibitory effect of curcumin on the Al (III)-induced Aβ42 aggregation and neurotoxicity in vitro. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2012; 1822(8): 1207–1215. doi: 10.1016/j.bbadis.2012.04.015

132. Mendonça LM, da Silva Machado C, Teixeira CCC, et al. Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells. Neurotoxicology 2013; 34: 205–211. doi: 10.1016/j.neuro.2012.09.011

133. Reddy ACP, Lokesh B. Effect of curcumin and eugenol on iron-induced hepatic toxicity in rats. Toxicology 1996; 107(1): 39–45. doi: 10.1016/0300-483X(95)03199-P

134. Sood S, Jain K, Gowthamarajan K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids and Surfaces B: Biointerfaces 2014; 113: 330–337. doi: 10.1016/j.colsurfb.2013.09.030

135. Sudjarwo SA, Sudjarwo GW, Koerniasari. Protective effect of curcumin on lead acetate-induced testicular toxicity in Wistar rats. Research in Pharmaceutical Sciences 2017; 12(5): 381–390. doi: 10.4103/1735-5362.213983

136. DeBusk RM. Dietary supplements and cardiovascular disease. Current Atherosclerosis Reports 2000; 2(6): 508–514. doi: 10.1007/s11883-000-0051-y

137. Kawanishi S, Oikawa S, Murata M. Evaluation for safety of antioxidant chemopreventive agents. Antioxidants & Redox Signaling 2005; 7(11–12): 1728–1739. doi: 10.1089/ars.2005.7.1728

138. Di Martino RMC, Luppi B, Bisi A, et al. Recent progress on curcumin-based therapeutics: A patent review (2012–2016). Part I: Curcumin. Expert Opinion on Therapeutic Patents 2017; 27(5): 579–590. doi: 10.1080/13543776.2017.1276566

139. Di Martino RMC, Luppi B, Bisi A, et al. Recent progress on curcumin-based therapeutics: a patent review (2012–2016). Part II: Curcumin derivatives in cancer and neurodegeneration. Expert Opinion on Therapeutic Patents 2017; 27(8): 953–965. doi: 10.1080/13543776.2017.1339793

140. Robbins PF, Rosenberg SA, Zhu S, et al. T Cell Receptors Recognizing hla-a1-restricted Mage-a3. U.S. Patent 20220195008A1, 23 June 2022.

141. Gey A, Tartour E, Bechard D. IL-15 and IL-15R-Alfa-Sushi Domain-based Modulokines. DK Patent 3030575T3, 22 October 2018.

142. Chen Y, Huang X, Kim S. Combination therapy for the treatment of cancer. 2019, Google Patents.

143. June CH, Zhao Y. RNA Engineered T Cells for the Treatment of Cancer. U.S. Patent 10421960B2, 24 September 2019.

144. Roberts DD, Pantoja DRS. Methods for Modulating Chemotherapeutic Cytotoxicity. U.S. Patent 11285169B2, 29 March 2022.

145. Anand N, Kaur S, Sabharwa S, et al. An overview of “Kanchnar” (Bauhinia variegata). International Journal of Research and Analytical Reviews 2018; 5(4): 997–1003.

146. Korman AJ, Lonberg N, Fontana DJ, et al. Combination of Anti-LAG-3 Antibodies and Anti-PD-1 Antibodies to Treat Tumors. SG Patent 11201601763SA, 28 April 2016.

147. Mortimer SAW, Talasaz A, Chudova D, et al. Methods for Early Detection of Cancer. U.S. Patent 20190085406A1, 21 March 2019.

148. Clube J. Selectively Altering Microbiota for Immune Modulation. U.S. Patent 10300138B2, 28 May 2019.

149. Mahr A, Weinschenk T, Schoor O, et al. Novel Peptides and Combination of Peptides and Scaffolds for Use in Immunotherapy Against Renal Cell Carcinoma (rcc) and Other Cancers. WO Patent 2016156230A1, 06 October 2016.

150. Manie E, Stern MH, Popova T. Methods for Detecting Inactivation of The Homologous Recombination Pathway (BRCA1/2) in Human Tumors. U.S. Patent 11149316B2, 19 October 2021.

151. Available online: https://patents.google.com/patent/US20220003792A1/en?oq=US+2022%2f0003792+A1 (accessed on 3 November 2023).

152. Huang CY, Wei PL, Prince GMSH, et al. The role of thrombomodulin in estrogen-receptor-positive breast cancer progression, metastasis, and curcumin sensitivity. Biomedicines 2023; 11(5): 1384. doi: 10.3390/biomedicines11051384

153. de Waure C, Bertola C, Baccarini G, et al. Exploring the contribution of curcumin to cancer therapy: a systematic review of randomized controlled trials. Pharmaceutics 2023; 15(4): 1275. doi: 10.3390/pharmaceutics15041275

154. Wang Y, Yu J, Cui R, et al. Curcumin in Treating Breast Cancer: A Review. Journal of Laboratory Automation 2016; 21(6): 723–731. doi: 10.1177/2211068216655524

155. Liu D, Chen Z. The effect of curcumin on breast cancer cells. Journal of Breast Cancer 2013; 16(2): 133–137. doi: 10.4048/jbc.2013.16.2.133