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Non-systemic Approaches for Ductal Carcinoma In Situ: Exploring the Potential of Ultra-flexible Combisomes as a Novel Drug Delivery Strategy—a Review

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Abstract

Ductal carcinoma in situ (DCIS) is currently treated through breast-conserving surgery (lumpectomy), radiation therapy, breast-removing surgery (mastectomy), and hormone therapy to prevent further progression into invasive breast cancer and recurrence. Discrepancies concerning the prognosis of DCIS have sparked controversy about adequate treatment. Considering the severe medical and psychological consequences of mastectomy, developing a treatment approach that arrests the progression of DCIS to the invasive stage without affecting the non-cancerous cells is of utmost importance. In the current review, the problems associated with the diagnosis and management of DCIS have been thoroughly discussed. A summary of the route of administration and drug delivery systems to manage DCIS was also provoked. Innovative ultra-flexible combisomes were also proposed for the effective management of DCIS. Prevention is essential in managing the risk of DCIS and reducing the risk of progression to invasive breast cancer. While prevention is vital, it is not always possible to prevent DCIS, and in some cases, treatment may be necessary. Hence, this review recommends that ultra-flexible combisomes administered as a topical gel provide a non-systemic approach for managing DCIS and thus significantly minimize the side effects and costs associated with existing therapies.

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References

  1. Sinn HP, Kreipe H. A brief overview of the WHO classification of breast tumors, 4th edition, focusing on issues and updates from the 3rd edition. Breast Care [Internet]. 2013;8:149–54. Available from: https://www.karger.com/Article/FullText/350774. Accessed 12-01-2023.

  2. Hindle W. Breast Care: A Clinical Guidebook for Women’s Primary Health Care Providers. New York: Springer-Verlag; 1999.

    Book  Google Scholar 

  3. Breast Cancer Stages [Internet]. Quest Cure. 2014 [cited 2022 Aug 1]. p. 85. Available from: https://www.breastcancer.org/pathology-report/breast-cancer-stages.

  4. Welch HG, Woloshin S, Schwartz LM. The sea of uncertainty surrounding ductal carcinoma in situ - The price of screening mammography. J Natl Cancer Inst United States; 2008;100:228–9.

  5. Breast Ductal Carcinoma in Situ - StatPearls - NCBI Bookshelf [Internet]. [cited 2022 Jul 26]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567766/?report=reader.

  6. World-Health-Rankings. Breast Cancer Death Rate By Country [Internet]. 2014 [cited 2023 Feb 4]. Available from: http://www.worldlifeexpectancy.com/world-health-rankings.

  7. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin United States. 2020;70:7–30.

    Article  Google Scholar 

  8. Chlebowski RT, Anderson GL, Gass M, Lane DS, Aragaki AK, Kuller LH, et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA J Am Med Assoc. 2010;304:1684–92.

    Article  CAS  Google Scholar 

  9. Tomlinson-Hansen S, Khan M, Cassaro S. Breast ductal carcinoma in situ. Treasure Island (FL); 2022.

  10. Stanciu-Pop C, Nollevaux MC, Berlière M, Duhoux FP, Fellah L, Galant C, et al. Morphological intratumor heterogeneity in ductal carcinoma in situ of the breast. Virchows Arch Germany. 2021;479:33–43.

    Article  Google Scholar 

  11. van Seijen M, Lips EH, Thompson AM, Nik-Zainal S, Futreal A, Hwang ES, et al. Ductal carcinoma in situ: to treat or not to treat, that is the question. Br J Cancer. 2019;121:285–92.

  12. Partridge A, Adloff K, Blood E, Dees EC, Kaelin C, Golshan M, et al. Risk perceptions and psychosocial outcomes of women with ductal carcinoma in situ: longitudinal results from a cohort study. J Natl Cancer Inst United States. 2008;100:243–51.

    Article  Google Scholar 

  13. Ganz PA. Quality-of-life issues in patients with ductal carcinoma in situ. J Natl Cancer Inst Monogr. 2010;2010:218–22.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Olov N, Bagheri-Khoulenjani S, Mirzadeh H. Combinational drug delivery using nanocarriers for breast cancer treatments: a review. J Biomed Mater Res Part A United States; 2018;106:2272–83.

  15. Wong HL, Bendayan R, Rauth AM, Li Y, Wu XY. Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles. Adv Drug Deliv Rev Netherlands. 2007;59:491–504.

    Article  CAS  Google Scholar 

  16. Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. United States; 2012;63:185–98.

  17. Kurtz SL, Lawson LB. Liposomes enhance dye localization within the mammary ducts of porcine nipples. Mol Pharm. 2019;16:1703–13.

    Article  CAS  PubMed  Google Scholar 

  18. Nayak D, Tippavajhala VK. A comprehensive review on preparation, evaluation and applications of deformable liposomes. Iran J Pharm Res 2021;20:186–205.

  19. Dershaw DD, Abramson A, Kinne DW. Ductal carcinoma in situ: mammographic findings and clinical implications. Radiology. United States; 1989;170:411–5.

  20. Holland R, Schuurmans Stekhoven JH, Hendriks JHCL, Verbeek ALM, Mravunac M. Extent, distribution, and mammographic/ histological correlations of breast ductal carcinoma in situ. Lancet. England; 1990;335:519–22.

  21. Mannu GS, Wang Z, Broggio J, Charman J, Cheung S, Kearins O, et al. Invasive breast cancer and breast cancer mortality after ductal carcinoma in situ in women attending for breast screening in England, 1988–2014: Population based observational cohort study. BMJ. 2020;369: m1570.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bijker N, Peterse JL, Duchateau L, Julien JP, Fentiman IS, Duval C, et al. Risk factors for recurrence and metastasis after breast-conserving therapy for ductal carcinoma-in-situ: analysis of European Organization for Research and Treatment of Cancer Trial 10853. J Clin Oncol. United States; 2001;19:2263–71.

  23. Garg PK, Jakhetiya A, Pandey R, Chishi N, Pandey D. Adjuvant radiotherapy versus observation following lumpectomy in ductal carcinoma in-situ: a meta-analysis of randomized controlled trials. Breast J. United States; 2018;24:233–9.

  24. Allred DC, Anderson SJ, Paik S, Wickerham DL, Nagtegaal ID, Swain SM, et al. Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a study based on NSABP protocol B-24. J Clin Oncol. 2012;30:1268–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lewis JS, Jordan VC. Selective estrogen receptor modulators (SERMs): Mechanisms of anticarcinogenesis and drug resistance. Mutat Res Fundam Mol Mech Mutagen. Netherlands; 2005;591:247–63.

  26. Laura C Collins MdcL. Ductal carcinoma in situ: treatment and prognosis - UpToDate [Internet]. 2021 [cited 2022 Aug 1]. Available from: https://www-uptodate-com.e-revistas.ugto.mx/contents/ductal-carcinoma-in-situ-treatment-and-prognosis?search=carcinomainsitutreatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1.

  27. Johnston SRD. New strategies in estrogen receptor-positive breast cancer. Clin Cancer Res. United States; 2010;16:1979–87.

  28. Fabian C, Tilzer L, Sternson L. Comparative binding affinities of tamoxifen, 4‐hydroxytamoxifen, and desmethyltamoxifen for estrogen receptors isolated from human breast carcinoma: Correlation with blood levels in patients with metastatic breast cancer. Biopharm Drug Dispos. England; 1981;2:381–90.

  29. Lee O, Ivancic D, Chatterton RT, Rademaker AW, Khan SA. In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast. Breast Cancer Targets Ther. 2011;3:61–70.

    Article  CAS  Google Scholar 

  30. Ganz PA, Cecchini RS, Julian TB, Margolese RG, Costantino JP, Vallow LA, et al. Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): A randomised, double-blind, phase 3 clinical trial. Lancet. 2016;387:857–65.

    Article  CAS  PubMed  Google Scholar 

  31. Kauffmann RM, Goldstein L, Marcinkowski E, Somlo G, Yuan Y, Ituarte PHG, et al. Predictors of antiestrogen recommendation in women with estrogen receptor-positive ductal carcinoma in situ. JNCCN J Natl Compr Cancer Netw. 2016;14:1081–90.

    Article  CAS  Google Scholar 

  32. Jordan VC. Chemoprevention of breast cancer with selective oestrogen-receptor modulators. Nat Rev Cancer. England; 2007;7:46–53.

  33. Fisher DE, Henderson IC, Schnitt SJ, Christian R, Harris JR. Chest wall recurrence of ductal carcinoma in situ of the breast after mastectomy. Cancer. United States; 1993;71:3025–8.

  34. Silverstein MJ, Barth A, Poller DN, Gierson ED, Colburn WJ, Waisman JR, et al. Ten-year results comparing mastectomy to excision and radiation therapy for ductal carcinoma in situ of the breast. Eur J Cancer. England; 1995;31:1425–7.

  35. Solin LJ, Kurtz J, Fourquet A, Amalric R, Recht A, Bornstein BA, et al. Fifteen-year results of breast-conserving surgery and definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast. J Clin Oncol. United States; 1996;14:754–63.

  36. Schnitt SJ, Silen W, Sadowsky NL, Connolly JL, Harris JR. Ductal carcinoma in situ (intraductal carcinoma) of the breast. N Engl J Med. United States; 1988;318:898–903.

  37. Chowdhury N, Vhora I, Patel K, Bagde A, Kutlehria S, Singh M. development of hot melt extruded solid dispersion of tamoxifen citrate and resveratrol for synergistic effects on breast cancer cells. AAPS PharmSciTech. 2018;19:3287–97.

    Article  CAS  PubMed  Google Scholar 

  38. Tchou J, Hou N, Rademaker A, Jordan VC, Morrow M. Acceptance of tamoxifen chemoprevention by physicians and women at risk. Cancer. United States; 2004;100:1800–6.

  39. Yen TWF, Hunt KK, Mirza NQ, Thomas ES, Singletary SE, Babiera G V., et al. Physician recommendations regarding tamoxifen and patient utilization of tamoxifen after surgery for ductal carcinoma in situ. Cancer. United States; 2004;100:942–9.

  40. Port ER, Montgomery LL, Heerdt AS, Borgen PI. Patient reluctance toward tamoxifen use for breast cancer primary prevention. Ann Surg Oncol. United States; 2001;8:580–5.

  41. Melnikow J, Paterniti D, Azari R, Kuenneth C, Birch S, Kuppermann M, et al. Preferences of women evaluating risks of tamoxifen (POWER) study of preferences for tamoxifen for breast cancer risk reduction. Cancer. United States; 2005;103:1996–2005.

  42. Clarke R, Liu MC, Bouker KB, Gu Z, Lee RY, Zhu Y, et al. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene. England; 2003;22:7316–39.

  43. Roxana S, Ioannis B, Evelyn D, Elke K, Michaela B, Joerg W, et al. Polypoid endometriosis in a postmenopausal woman treated with tamoxifen due to DCIS: a case report and review of the literature. Arch Clin Biomed Res [Internet]. 2020 [cited 2022 Jul 23];04. Available from: https://www.fortunejournals.com/articles/polypoid-endometriosis-in-a-postmenopausal-woman-treated-with-tamoxifen-due-to-dcis-a-case-report-and-review-of-the-literature.html.

  44. Novick AM, Scott AT, Neill Epperson C, Schneck CD. Neuropsychiatric effects of tamoxifen: challenges and opportunities. Front Neuroendocrinol. 2020;59:100869.

  45. Gail MH, Costantino JP, Bryant J, Croyle R, Freedman L, Helzlsouer K, et al. Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J Natl Cancer Inst. United States; 1999;91:1829–46.

  46. Tsuda M, Takano Y, Shigeyasu C, Imoto S, Yamada M. Abnormal corneal lesions induced by trastuzumab emtansine: an antibody-drug conjugate for breast cancer. Cornea. United States; 2016;35:1378–80.

  47. Kuerer HM, Buzdar AU, Mittendorf EA, Esteva FJ, Lucci A, Vence LM, et al. Biologic and immunologic effects of preoperative trastuzumab for ductal carcinoma in situ of the breast. Cancer. 2011;117:39–47.

    Article  CAS  PubMed  Google Scholar 

  48. Pondé N, Amaye L, Lambertini M, Paesmans M, Piccart M, de Azambuja E. Trastuzumab emtansine (T-DM1)-associated cardiotoxicity: pooled analysis in advanced HER2-positive breast cancer. Eur J Cancer. 2020;126:65–73.

    Article  PubMed  Google Scholar 

  49. Acibuca A, Sezer A, Yilmaz M, Sumbul AT, Demircan S, Muderrisoglu IH, et al. Cardiotoxicity of trastuzumab emtansine (T-DM1): a single-center experience. J Int Med Res. 2021;49:3000605211053755.

  50. Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: A randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. England; 2013;24:2278–84.

  51. Yassemi A, Kashanian S, Zhaleh H. Folic acid receptor-targeted solid lipid nanoparticles to enhance cytotoxicity of letrozole through induction of caspase-3 dependent-apoptosis for breast cancer treatment. Pharm Dev Technol. 2020;25:397–407.

    Article  CAS  PubMed  Google Scholar 

  52. Radwan R, Abdelkader A, Fathi HA, Elsabahy M, Fetih G, El-Badry M. Development and evaluation of letrozole-loaded hyaluronic acid/chitosan-coated poly(d, l-lactide-co-glycolide) nanoparticles. J Pharm Innov. 2022;17:572–83.

    Article  Google Scholar 

  53. Miller AP, Black M, Amengual J. Fenretinide inhibits vitamin a formation from β-carotene and regulates carotenoid levels in mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2022;1867:159070.

  54. Morales-Conde M, López-Ibáñez N, Calvete-Candenas J, Mendonça FMI. Fulvestrant-induced toxic epidermal necrolysis. An Bras Dermatol. 2019;94:218–20.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Schlotman A, Stater A, Schuler K, Heideman J, Abramson V. Grade 3 hepatotoxicity following fulvestrant, palbociclib, and erdafitinib therapy in a patient with ER-positive/PR-negative/HER2-negative metastatic breast cancer: a case report. Case Rep Oncol. 2020;13:304–8.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Prathumsap N, Shinlapawittayatorn K, Chattipakorn SC, Chattipakorn N. Effects of doxorubicin on the heart: from molecular mechanisms to intervention strategies. Eur J Pharmacol. 2020;866:172818.

  57. Sheibani M, Azizi Y, Shayan M, Nezamoleslami S, Eslami F, Farjoo MH, et al. Doxorubicin-induced cardiotoxicity: an overview on pre-clinical therapeutic approaches. Cardiovasc Toxicol. 2022;22:292–310.

  58. Mohsen S, Sobash PT, Algwaiz GF, Nasef N, Al-Zeidaneen SA, Karim NA. Autophagy agents in clinical trials for cancer therapy: a brief review. Curr Oncol. 2022;29:1695–708.

  59. Al-Bari MAA. Co-targeting of lysosome and mitophagy in cancer stem cells with chloroquine analogues and antibiotics. J Cell Mol Med. 2020;24:11667–79.

  60. Jayaraman S, Reid JM, Hawse JR, Goetz MP. Endoxifen, an estrogen receptor targeted therapy: from bench to bedside. Endocrinol. (United States). 2021;162:bqab191.

  61. Singh SK, Singh S, Wlillard J, Singh R. Drug delivery approaches for breast cancer. Int J Nanomed. 2017;12:6205–18.

  62. Lee O, Khan SA. Novel routes for administering chemoprevention: Local transdermal therapy to the breasts. Semin Oncol. United States; 2016;43:107–15.

  63. Pujol H, Girault J, Rouanet P, Fournier S, Grenier J, Simony J, et al. Phase I Study of percutaneous 4-hydroxy-tamoxifen with analyses of 4-hydroxy-tamoxifen concentrations in breast cancer and normal breast tissue. Cancer Chemother Pharmacol. Germany; 1995;36:493–8.

  64. Rouanet P, Linares-Cruz G, Dravet F, Poujol S, Gourgou S, Simony-Lafontaine J, et al. Neoadjuvant percutaneous 4-hydroxytamoxifen decreases breast tumoral cell proliferation: A prospective controlled randomized study comparing three doses of 4-hydroxytamoxifen gel to oral tamoxifen. J Clin Oncol. United States; 2005;23:2980–7.

  65. Ackerman AB, Kessler G, Gyorfi T, Tsou HC, Gottlieb GJ. Contrary view: the breast is not an organ per se, but a distinctive region of skin and subcutaneous tissue. Am J Dermatopathol. United States; 2007;29:211–8.

  66. Lee O, Page K, Ivancic D, Helenowski I, Parini V, Sullivan ME, et al. A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in Situ of the breast. Clin Cancer Res. 2014;20:3672–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Li L, Xu X, Fang L, Liu Y, Sun Y, Wang M, et al. The transdermal patches for site-specific delivery of letrozole: a new option for breast cancer therapy. AAPS PharmSciTech. 2010;11:1054–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Gao X, Patel MG, Bakshi P, Sharma D, Banga AK. Enhancement in the transdermal and localized delivery of honokiol through breast tissue. AAPS PharmSciTech. 2018;19:3501–11.

    Article  CAS  PubMed  Google Scholar 

  69. Salata GC, Malagó ID, Lopes LB. A Lipid-based in situ-forming hexagonal phase for prolonged retention and drug release in the breast tissue. AAPS PharmSciTech. United States; 2022;23:260.

  70. Mahoney ME, Gordon EJ, Rao JY, Jin Y, Hylton N, Love SM. Intraductal therapy of ductal carcinoma in situ: a presurgery study. Clin Breast Cancer. 2013;13:280–6.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Pandey M, Wen PX, Ning GM, Xing GJ, Wei LM, Kumar D, et al. Intraductal delivery of nanocarriers for ductal carcinoma in situ treatment: a strategy to enhance localized delivery. Nanomedicine (Lond) [Internet]. England; 2023; Available from: http://www.ncbi.nlm.nih.gov/pubmed/36695306. Accessed 08-02-2023.

  72. Wang G, Chen C, Pai P, Korangath P, Sun S, Merino VF, et al. Intraductal fulvestrant for therapy of ERα-positive ductal carcinoma in situ of the breast: a preclinical study. Carcinogenesis. England; 2019;40:903–13.

  73. Stearns V, Mori T, Jacobs LK, Khouri NF, Gabrielson E, Yoshida T, et al. Breast cancer: Preclinical and clinical evaluation of intraductally administered agents in early breast cancer. Sci Transl Med. United States; 2011;3:106ra108.

  74. de Groot JS, van Diest PJ, van Amersfoort M, Vlug EJ, Pan X, ter Hoeve ND, et al. Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice. Oncotarget. 2017;8:60750–63

  75. Gu Z, Al-Zubaydi F, Adler D, Li S, Johnson S, Prasad P, et al. Evaluation of intraductal delivery of poly(ethylene glycol)-doxorubicin conjugate nanocarriers for the treatment of ductal carcinoma in situ (DCIS)-like lesions in rats. J Interdiscip Nanomed. 2018;3:146–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Al-Zubaydi F, Gao D, Kakkar D, Li S, Adler D, Holloway J, et al. Breast intraductal nanoformulations for treating ductal carcinoma in situ I: exploring metal-ion complexation to slow ciclopirox release, enhance mammary persistence and efficacy. J Control Release. Netherlands; 2020;323:71–82.

  77. Joseph MK, Islam M, Reineke J, Hildreth M, Woyengo T, Pillatzki A, et al. Intraductal drug delivery to the breast: effect of particle size and formulation on breast duct and lymph node retention. Mol Pharm. United States; 2020;17:441–52

  78. Dave K, Alsharif FM, Islam S, Dwivedi C, Perumal O. Chemoprevention of breast cancer by transdermal delivery of α-santalol through breast skin and mammary papilla (nipple). Pharm Res. United States; 2017;34:1897–907.

  79. Patil A, Narvenker R, Prabhakar B, Shende P. Strategic consideration for effective chemotherapeutic transportation via transpapillary route in breast cancer. Int J Pharm. Netherlands; 2020;586:119563.

  80. Dave K, Averineni R, Sahdev P, Perumal O. Transpapillary drug delivery to the breast. PLoS ONE. 2014;9: e115712.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Kurtz SL, Lawson LB. Nanoemulsions enhance in vitro transpapillary diffusion of model fluorescent dye Nile Red. Sci Rep. 2019;9:11810.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Cevc G, Blume G, Schätzlein A. Transfersomes-mediated transepidermal delivery improves the regio-specificity and biological activity of corticosteroids in vivo. J Control Release. 1997;45:211–26.

    Article  CAS  Google Scholar 

  83. Gupta A, Aggarwal G, Singla S, Arora R. Transfersomes: a novel vesicular carrier for enhanced transdermal delivery of sertraline: development, characterization, and performance evaluation. Sci Pharm. 2012;80:1061–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Jain S, Jain P, Umamaheshwari RB, Jain NK. Transfersomes - a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation. Drug Dev Ind Pharm. England; 2003;29:1013–26.

  85. Guimarães D, Cavaco-Paulo A, Nogueira E. Design of liposomes as drug delivery system for therapeutic applications. Int J Pharm. Elsevier; 2021;601:120571.

  86. Sudhakar K, Fuloria S, Subramaniyan V, Sathasivam KV, Azad AK, Swain SS, et al. Ultraflexible liposome nanocargo as a dermal and transdermal drug delivery system. Nanomaterials. 2021;11:1–20.

    Article  Google Scholar 

  87. Sundralingam U, Muniyandy S, Radhakrishnan AK, Palanisamy UD. Ratite oils for local transdermal therapy of 4-OH tamoxifen: development, characterization, and ex vivo evaluation. J Liposome Res. England; 2021;31:217–29.

  88. Sundralingam U, Chakravarthi S, Radhakrishnan AK, Muniyandy S, Palanisamy UD. Efficacy of emu oil transfersomes for local transdermal delivery of 4-oh tamoxifen in the treatment of breast cancer. Pharmaceutics. 2020;12:1–19.

    Article  Google Scholar 

  89. Chen M, Shamim MA, Shahid A, Yeung S, Andresen BT, Wang J, et al. Topical delivery of carvedilol loaded nano-transfersomes for skin cancer chemoprevention. Pharmaceutics. 2020;12:1–17.

    Article  CAS  Google Scholar 

  90. Bollareddy SR, Krishna V, Roy G, Dasari D, Dhar A, Venuganti VVK. Transfersome hydrogel containing 5-fluorouracil and etodolac combination for synergistic oral cancer treatment. AAPS PharmSciTech. United States; 2022;23:70.

  91. Abdel-Hafez SM, Hathout RM, Sammour OA. Curcumin-loaded ultradeformable nanovesicles as a potential delivery system for breast cancer therapy. Colloids Surfaces B Biointerfaces. Netherlands; 2018;167:63–72.

  92. Zeb A, Qureshi OS, Kim HS, Cha JH, Kim HS, Kim JK. Improved skin permeation of methotrexate via nanosized ultradeformable liposomes. Int J Nanomed. 2016;11:3813–24.

    Article  CAS  Google Scholar 

  93. Munekata PES, Pateiro M, Barba FJ, Dominguéz R, Gagaoua M, Lorenzo JM. Development of new food and pharmaceutical products: nutraceuticals and food additives. Adv Food Nutr Res. United States; 2020;92:53–96.

  94. Meng J, Guo F, Xu H, Liang W, Wang C, Da YX. Combination therapy using co-encapsulated resveratrol and paclitaxel in liposomes for drug resistance reversal in breast cancer cells in vivo. Sci Rep. 2016;6:22390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Dubey A, Shriram RG, El-Zahaby SA. A review on exploring better safety prospects in managing cancer using liposomal combinations of food bioactive compounds and anticancer drugs: combisomes. Curr Drug Deliv. United Arab Emirates; 2021;18:1105–20.

  96. Lee SJ, Jeong JH, Lee IH, Lee J, Jung JH, Park HY, et al. Effect of high-dose Vitamin C combined with anti-cancer treatment on breast cancer cells. Anticancer Res. Greece; 2019;39:751–8.

  97. Houdaihed L, Evans JC, Allen C. Codelivery of paclitaxel and everolimus at the optimal synergistic ratio: a promising solution for the treatment of breast cancer. Mol Pharm. United States; 2018;15:3672–81.

  98. Khamis AAA, Ali EMM, El-Moneim MAA, Abd-Alhaseeb MM, El-Magd MA, Salim EI. Hesperidin, piperine and bee venom synergistically potentiate the anticancer effect of tamoxifen against breast cancer cells. Biomed Pharmacother. France; 2018;105:1335–43.

  99. Li S, Yuan S, Zhao Q, Wang B, Wang X, Li K. Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it. Biomed Pharmacother. France; 2018;100:441–7.

  100. Nguyen NT, Nguyen NNT, Tran NTN, Le PN, Nguyen TBT, Nguyen NH, et al. Synergic activity against MCF-7 breast cancer cell growth of nanocurcumin-encapsulated and cisplatin-complexed nanogels. Molecules. 2018;23:3347.

  101. Elshal MF, Eid NM, El-Sayed I, El-Sayed W, Al-Karmalawy AA. Concanavalin-A shows synergistic cytotoxicity with tamoxifen via inducing apoptosis in estrogen receptor-positive breast cancer: in vitro and molecular docking studies. Pharm Sci. 2022;28:76–85.

    CAS  Google Scholar 

  102. Badawy AA, Othman RQA, El-Magd MA. Effect of combined therapy with camel milk-derived exosomes, tamoxifen, and hesperidin on breast cancer. Mol Cell Toxicol [Internet]. Springer Singapore; 2021; Available from: https://doi.org/10.1007/s13273-021-00163-4.

  103. Roy M, Mukherjee S, Sarkar R, Biswas J. Curcumin sensitizes chemotherapeutic drugs via modulation of PKC, telomerase, NF-κB and HDAC in breast cancer. Ther Deliv. England; 2011;2:1275–93.

  104. Zhan Y, Chen Y, Liu R, Zhang H, Zhang Y. Potentiation of paclitaxel activity by curcumin in human breast cancer cell by modulating apoptosis and inhibiting EGFR signaling. Arch Pharm Res. Korea (South); 2014;37:1086–95.

  105. Yu Y, Zhou Q, Hang Y, Bu X, Jia W. Antiestrogenic effect of 20S-protopanaxadiol and its synergy with tamoxifen on breast cancer cells. Cancer. United States; 2007;109:2374–82.

  106. Yaacob NS, Kamal NNNM, Norazmi MN. Synergistic anticancer effects of a bioactive subfraction of Strobilanthes crispus and tamoxifen on MCF-7 and MDA-MB-231 human breast cancer cell lines. BMC Complement Altern Med. 2014;14:252.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Li X, Gao B, Su X. Anticancer bioactive peptide combined with docetaxel and its mechanism in the treatment of breast cancer. Exp Ther Med. 2020;20:1917–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Choi YE, Park E. Ferulic acid in combination with PARP inhibitor sensitizes breast cancer cells as chemotherapeutic strategy. Biochem Biophys Res Commun. United States; 2015;458:520–4.

  109. Malhão F, Ramos AA, Macedo AC, Rocha E. Cytotoxicity of seaweed compounds, alone or combined to reference drugs, against breast cell lines cultured in 2d and 3d. Toxics. 2021;9:1–32.

    Article  Google Scholar 

  110. Molavi O, Narimani F, Asiaee F, Sharifi S, Tarhriz V, Shayanfar A, et al. Silibinin sensitizes chemo-resistant breast cancer cells to chemotherapy. Pharm Biol. 2017;55:729–39.

    Article  CAS  PubMed  Google Scholar 

  111. Singaraju M, Palaian S, Shankar PR, Shrestha S. Safety profile and toxicity amelioration strategies of common adverse effects associated with anticancer medications. J Pharm Res Int. 2020;32:18–30.

    Article  Google Scholar 

  112. Devulapally R, Sekar TV, Paulmurugan R. Formulation of anti-miR-21 and 4-hydroxytamoxifen co-loaded biodegradable polymer nanoparticles and their antiproliferative effect on breast cancer cells. Mol Pharm. 2015;12:2080–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Febriansah R, Putri DDP, Sarmoko, Nurulita NA, Meiyanto E, Nugroho AE. Hesperidin as a preventive resistance agent in MCF-7 breast cancer cells line resistance to doxorubicin. Asian Pac J Trop Biomed. 2014;4:228–33.

  114. Yap KM, Sekar M, Wu YS, Gan SH, Rani NNIM, Seow LJ, et al. Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi J Biol Sci. 2021;28:6730–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Topical afimoxifene in treating patients with breast cancer who have undergone radiation therapy on one breast [Internet]. Case Med. Res. 2019 [cited 2022 Jul 23]. Available from: https://clinicaltrials.gov/ct2/show/ NCT04009044.

  116. Testing an active form of tamoxifen (4-hydroxytamoxifen) delivered through the breast skin to control ductal carcinoma in situ (DCIS) of the breast [Internet]. Phase IIB pre-surgical trial oral tamoxifen versus transdermal 4-hydroxytamoxifen women with DCIS breast. 2016 [cited 2022 Aug 1]. Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=cctr&NEWS=N&AN=CN-01560632

  117. Oral tamoxifen vs. TamGel vs. control in women with atypical hyperplasia or lobular carcinoma in situ - full text view - ClinicalTrials.gov [Internet]. [cited 2022 Aug 1]. Available from: https://clinicaltrials.gov/ct2/show/ NCT04570956

  118. Search of: topical | Breast Cancer Female - List Results - ClinicalTrials.gov [Internet]. [cited 2022 Jul 27]. Available from: https://www.clinicaltrials.gov/ct2/results?cond=Breast+Cancer+Female&term=topical+&cntry=&state=&city=&dist=.

  119. Search of: topical | Breast Cancer, Stage 0 - List Results - ClinicalTrials.gov [Internet]. [cited 2022 Jul 27]. Available from: https://www.clinicaltrials.gov/ct2/results?cond=Breast+Cancer%2C+Stage+0&term=topical+&cntry=&state=&city=&dist=.

  120. 4-Hydroxytamoxifen or tamoxifen citrate in treating women with newly diagnosed ductal breast carcinoma in situ [Internet]. Clinicaltrials.Gov. 2010 [cited 2022 Jul 23]. p. 12/1/2010-2/1/2016. Available from: http://clinicaltrials.gov/show/ NCT00952731.

  121. Bexarotene in preventing breast cancer in patients at high risk for breast cancer - full text view - ClinicalTrials.gov [Internet]. [cited 2022 Jul 23]. Available from: https://clinicaltrials.gov/ct2/show/study/ NCT03323658.

  122. Afimoxifene in reducing the risk of breast cancer in women with mammographically dense breast - full text view - ClinicalTrials.gov [Internet]. [cited 2022 Aug 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03063619?cond=Afimoxifene+in+Reducing+the+Risk+of+Breast+Cancer+in+Women+With+Mammographically+Dense+Breast&draw=2&rank=1

  123. A pre-surgical PK study of IM and intraductally delivered fulvestrant - full text view - ClinicalTrials.gov [Internet]. [cited 2022 Jul 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02540330?term=NCT02540330&draw=2&rank=1.

  124. Doxorubicin hydrochloride liposome in treating women with ductal carcinoma in situ undergoing surgery [Internet]. Clinicaltrials.Gov. 2008 [cited 2022 Jul 23]. p. 2/1/2008. Available from: http://clinicaltrials.gov/show/ NCT00671476.

  125. Study of intraductal carboplatin in women with ductal carcinoma in situ (DCIS) [Internet]. Clinicaltrials.Gov. 2008 [cited 2022 Jul 23]. p. 5/1/2008-12/1/2009. Available from: http://clinicaltrials.gov/show/ NCT00669747.

  126. Study of the efficacy of chloroquine in the treatment of ductal carcinoma in situ (The PINC Trial) - full text view - ClinicalTrials.gov [Internet]. [cited 2022 Jul 23]. Available from: https://clinicaltrials.gov/ct2/show/ NCT01023477.

  127. Pembrolizumab in high-risk ductal carcinoma in situ (DCIS) - full text view - ClinicalTrials.gov [Internet]. [cited 2022 Jul 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02872025?term=NCT02872025&draw=1&rank=1

  128. Topical Endoxifen in Women - Full Text View - ClinicalTrials.gov [Internet]. [cited 2022 Aug 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT04616430?cond=Topical+Endoxifen+in+Women&draw=1&rank=1

  129. Phase I trial of endoxifen gel versus placebo in women undergoing breast surgery [Internet]. https://clinicaltrials.gov/show/ NCT03317405. 2017 [cited 2022 Jul 23]. Available from: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-01565052/full.

  130. Banga AK. Microporation applications for enhancing drug delivery. Expert Opin Drug Deliv. 2009. p. 343–54.

  131. Khan S, Hasan A, Attar F, Babadaei MMN, Zeinabad HA, Salehi M, et al. Diagnostic and drug release systems based on microneedle arrays in breast cancer therapy. J Control Release [Internet]. Elsevier B.V.; 2021;338:341–57. Available from: https://doi.org/10.1016/j.jconrel.2021.08.036.

  132. Zamani M, Rostamizadeh K, Kheiri Manjili H, Danafar H. In vitro and in vivo biocompatibility study of folate-lysine-PEG-PCL as nanocarrier for targeted breast cancer drug delivery. Eur Polym J [Internet]. 2018;103:260–70. Available from: https://doi.org/10.1016/j.eurpolymj.2018.04.020.

  133. Batool A, Arshad R, Razzaq S, Nousheen K, Kiani MH, Shahnaz G. Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer. Int J Biol Macromol [Internet]. Elsevier B.V; 2020;152:503–15. Available from: https://doi.org/10.1016/j.ijbiomac.2020.02.275.

  134. Vivek R, Nipun Babu V, Thangam R, Subramanian KS, Kannan S. PH-responsive drug delivery of chitosan nanoparticles as Tamoxifen carriers for effective anti-tumor activity in breast cancer cells. Colloids Surfaces B Biointerfaces [Internet]. Elsevier B.V.; 2013;111:117–23. Available from: https://doi.org/10.1016/j.colsurfb.2013.05.018.

  135. Gharbavi M, Johari B, Eslami SS, Mousazadeh N, Sharafi A. Cholesterol-conjugated bovine serum albumin nanoparticles as a tamoxifen tumor-targeted delivery system [Internet]. Cell Biol. Int. John Wiley & Sons, Ltd; 2020. Available from: https://doi.org/10.1002/cbin.11455.

  136. Wang X, Chen X, Yang X, Gao W, He B, Dai W, et al. A nanomedicine based combination therapy based on QLPVM peptide functionalized liposomal tamoxifen and doxorubicin against Luminal A breast cancer. Nanomedicine Nanotechnology, Biol Med [Internet]. Elsevier Inc.; 2016;12:387–97. Available from: https://doi.org/10.1016/j.nano.2015.12.360.

  137. Jain AS, Goel PN, Shah SM, Dhawan V V., Nikam Y, Gude RP, et al. Tamoxifen guided liposomes for targeting encapsulated anticancer agent to estrogen receptor positive breast cancer cells: In vitro and in vivo evaluation. Biomed Pharmacother [Internet]. Elsevier Masson SAS; 2014;68:429–38. Available from: https://doi.org/10.1016/j.biopha.2014.03.004.

  138. Nankali E, Shaabanzadeh M, Torbati MB. Fluorescent tamoxifen-encapsulated nanocapsules functionalized with folic acid for enhanced drug delivery toward breast cancer cell line MCF-7 and cancer cell imaging. Naunyn Schmiedebergs Arch Pharmacol. 2020;393:1211–9.

  139. Reddy BS, Banerjee R. 17β-estradiol-associated stealth-liposomal delivery of anticancer gene to breast cancer cells. Angew Chem. 2005;117:6881–5.

    Article  Google Scholar 

  140. Bhagwat GS, Athawale RB, Gude RP, Md S, Alhakamy NA, Fahmy UA, et al. Formulation and development of transferrin targeted solid lipid nanoparticles for breast cancer therapy. Front Pharmacol. 2020;11:1–12.

    Article  Google Scholar 

  141. Ibrahim OM, El-Deeb NM, Abbas H, Elmasry SM, El-Aassar MR. Alginate based tamoxifen/metal dual core-folate decorated shell: Nanocomposite targeted therapy for breast cancer via ROS-driven NF-κB pathway modulation. Int J Biol Macromol. Netherlands; 2020;146:119–31.

  142. Abu Lila AS, Soliman MS, Kiran HC, Gangadharappa H V., Younes KM, Khafagy ES, et al. Tamoxifen-loaded functionalized graphene nanoribbons for breast cancer therapy. J Drug Deliv Sci Technol [Internet]. Elsevier B.V.; 2021;63:102499. Available from: https://doi.org/10.1016/j.jddst.2021.102499.

  143. Nokhodi F, Nekoei M, Goodarzi MT. Hyaluronic acid-coated chitosan nanoparticles as targeted-carrier of tamoxifen against MCF7 and TMX-resistant MCF7 cells. J Mater Sci Mater Med. Springer US; 2022;33.

  144. Kim CH, Lee SG, Kang MJ, Lee S, Choi YW. Surface modification of lipid-based nanocarriers for cancer cell-specific drug targeting. J Pharm Investig. 2017. p. 203–27.

  145. Bashyal S, Noh G, Keum T, Choi YW, Lee S. Cell penetrating peptides as an innovative approach for drug delivery; then, present and the future. J. Pharm. Investig. 2016. p. 205–20.

  146. Gronewold A, Horn M, Ranđelović I, Tóvári J, Muñoz Vázquez S, Schomäcker K, et al. Characterization of a cell-penetrating peptide with potential anticancer activity. ChemMedChem. Germany; 2017;12:42–9.

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  1. Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Deralakatte, Mangalore, 575018, India

    Cynthia Lizzie Lobo, Amitha Shetty, Manohar M & Akhilesh Dubey

  2. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Salman International University, South Sinai, Egypt

    Sally A. El-Zahaby

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Conception and design have been done by Cynthia Lizzie Lobo and Akhilesh Dubey. Writing, reviewing and revising the manuscript have been done by Amitha Shetty, Manohar M, Sally A. EL-Zahaby and Akhilesh Dubey. Figures- design and concept by Manohar M, Cynthia Lizzie Lobo and Sally El-Zahaby. All authors have seen the manuscript and have agreed to the submission.

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Lobo, C.L., Shetty, A., M, M. et al. Non-systemic Approaches for Ductal Carcinoma In Situ: Exploring the Potential of Ultra-flexible Combisomes as a Novel Drug Delivery Strategy—a Review. AAPS PharmSciTech 24, 119 (2023). https://doi.org/10.1208/s12249-023-02574-z

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