Intraductal Therapy in Breast Cancer: Current Status and Future Prospective


With our improved understanding of the biological behavior of breast cancer, minimally invasive intervention is urgently needed for personalized treatment of early disease. Intraductal therapy is one such minimally invasive approach. With the help of appropriate tools, technologies using the intraductal means of entering the ducts may be used both to diagnose and treat lesions in the mammary duct system with less trauma and at the same time avoid systemic toxicity. Traditional agents such as those targeting pathways, endocrine therapy, immunotherapy, or gene therapy can be used alone or combined with other new technologies, such as nanomaterials, through the intraductal route. Additionally, relevant mammary tumor models in rodents which reflect changes in the tumor microenvironment will help deepen our understanding of their biological behavior and heterogeneity. This article reviews the current status and future prospects of intraductal therapy in breast cancer, with emphasis on ductal carcinoma in situ.

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  1. 1.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et al. Breast cancer statistics, 2019. CA Cancer J Clin. 2019;69:438–51.

    Article  PubMed  Google Scholar 

  3. 3.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Chen C, Sun S, Yuan JP, Wang YH, Cao TZ, Zheng HM, et al. Characteristics of breast cancer in Central China, literature review and comparison with USA. Breast. 2016;30:208–13.

    Article  PubMed  Google Scholar 

  6. 6.

    Burstein HJ, Polyak K, Wong JS, Lester SC, Kaelin CM. Ductal carcinoma in situ of the breast. N Engl J Med. 2004;350:1430–41.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Silverstein MJ. Ductal carcinoma in situ of the breast. Annu Rev Med. 2000;51:17–32.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Tot T. DCIS, cytokeratins, and the theory of the sick lobe. Virchows Arch. 2005;447:1–8.

    Article  PubMed  Google Scholar 

  9. 9.

    Tot T. The theory of the sick breast lobe and the possible consequences. Int J Surg Pathol. 2007;15:369–75.

    Article  PubMed  Google Scholar 

  10. 10.

    Peterson JL, Vallow LA, Hines SL, Buskirk SJ. Ductal carcinoma in situ of the breast. Oncol Rev. 2009;3:237–46.

    Article  Google Scholar 

  11. 11.

    Tot T. Correlating the ground truth of mammographic histology with the success or failure of imaging. Technol Cancer Res Treat. 2005;4:23–8.

    Article  PubMed  Google Scholar 

  12. 12.

    Love SM, Barsky SH. Anatomy of the nipple and breast ducts revisited. Cancer. 2004;101(9):1947–57.

    Article  Google Scholar 

  13. 13.

    Ramsay DT, Kent JC, Hartmann RA, Hartmann PE. Anatomy of the lactating human breast redefined with ultrasound imaging. J Anat. 2005;206(6):525–34.

    CAS  Article  Google Scholar 

  14. 14.

    Going JJ, Moffat DF. Escaping from flatland: clinical and biological aspects of human mammary duct anatomy in three dimensions. J Pathol. 2004;203(1):538–44.

    Article  Google Scholar 

  15. 15.

    King BL, Love SM. The intraductal approach to the breast: raison d'être. Breast Cancer Res. 2006;8:206.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Richard E, Grellety T, Velasco V, MacGrogan G, Bonnefoi H, Iggo R. The mammary ducts create a favourable microenvironment for xenografting of luminal and molecular apocrine breast tumours. J Pathol. 2016;240(3):256–61.

    CAS  Article  Google Scholar 

  17. 17.

    Fiche M, Scabia V, Aouad P, Battista L, Treboux A, Stravodimou A, et al. Intraductal patient-derived xenografts of estrogen receptor α-positive breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions. J Pathol. 2019;247(3):287–92.

    CAS  Article  Google Scholar 

  18. 18.

    Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347:567–75.

    Article  PubMed  Google Scholar 

  19. 19.

    Dooley WC. Routine operative breast endoscopy during lumpectomy. Ann Surg Oncol. 2003;10:38–42.

    Article  PubMed  Google Scholar 

  20. 20.

    Going JJ, Mohun TJ. Human breast duct anatomy, the 'sick lobe' hypothesis and intraductal approaches to breast cancer. Breast Cancer Res Treat. 2006;97:285–91.

    Article  PubMed  Google Scholar 

  21. 21.

    Page DL, Schuyler PA, Dupont WD, Jensen RA, Plummer WD Jr, Simpson JF. Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study. Lancet. 2003;361:125–9.

    Article  PubMed  Google Scholar 

  22. 22.

    Trujillo KA, Hines WC, Vargas KM, Jones AC, Joste NE, Bisoffi M, et al. Breast field cancerization: isolation and comparison of telomerase-expressing cells in tumor and tumor adjacent, histologically normal breast tissue. Mol Cancer Res. 2011;9(9):1209–21.

    CAS  Article  Google Scholar 

  23. 23.

    Trujillo KA, Heaphy CM, Mai M, Vargas KM, Jones AC, Vo P, et al. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors. Int J Cancer. 2011;129(6):1310–21.

    CAS  Article  Google Scholar 

  24. 24.

    Wang F, Yang Y, Fu Z, Xu N, Chen F, Yin H, et al. Differential DNA methylation status between breast carcinomatous and normal tissues. Biomed Pharmacother. 2014;68(6):699–707.

    CAS  Article  Google Scholar 

  25. 25.

    Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH. A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63(8):1727–30.

    CAS  PubMed  Google Scholar 

  26. 26.

    Harper S, Lynch J, Meersman SC, Breen N, Davis WW, Reichman MC. Trends in area-socioeconomic and race-ethnic disparities in breast cancer incidence, stage at diagnosis, screening, mortality, and survival among women ages 50 years and over (1987-2005). Cancer Epidemiol Biomark Prev. 2009;18:121–31.

    Article  Google Scholar 

  27. 27.

    Yan PS, Venkataramu C, Ibrahim A, Liu JC, Shen RZ, Diaz NM, et al. Mapping geographic zones of cancer risk with epigenetic biomarkers in normal breast tissue. Clin Cancer Res. 2006;12:6626–36.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Zardavas D, Irrthum A, Swanton C, Piccart M. Clinical management of breast cancer heterogeneity. Nat Rev Clin Oncol. 2015;12:381–94.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Bahcecioglu G, Basara G, Ellis BW, Ren X, Zorlutuna P. Breast cancer models: engineering the tumor microenvironment. Acta Biomater. 2020;106:1–21.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Behbod F, Kittrell FS, LaMarca H, Edwards D, Kerbawy S, Heestand JC, et al. An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ. Breast Cancer Res. 2009;11:R66.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Valdez KE, Fan F, Smith W, Allred DC, Medina D, Behbod F. Human primary ductal carcinoma in situ (DCIS) subtype-specific pathology is preserved in a mouse intraductal (MIND) xenograft model. J Pathol. 2011;225:565–73.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Sflomos G, Dormoy V, Metsalu T, Jeitziner R, Battista L, Scabia V, et al. A preclinical model for ERα-positive breast Cancer points to the epithelial microenvironment as determinant of luminal phenotype and hormone response. Cancer Cell. 2016;29:407–22.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    DEOME KB, Jr FAULKINLJ, BERN HA, BLAIR PB. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res. 1959;19:515–20.

  34. 34.

    Eirew P, Stingl J, Raouf A, Turashvili G, Aparicio S, Emerman JT, et al. A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability. Nat Med. 2008;14:1384–9.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Okugawa H, Yamamoto D, Uemura Y, Sakaida N, Tanano A, Tanaka K, et al. Effect of perductal paclitaxel exposure on the development of MNU-induced mammary carcinoma in female S-D rats. Breast Cancer Res Treat. 2005;91:29–34.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Murata S, Kominsky SL, Vali M, Zhang Z, Garrett-Mayer E, Korz D, et al. Ductal access for prevention and therapy of mammary tumors. Cancer Res. 2006;66:638–45.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

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

  38. 38.

    Chun YS, Bisht S, Chenna V, Pramanik D, Yoshida T, Hong SM, et al. Intraductal administration of a polymeric nanoparticle formulation of curcumin (NanoCurc) significantly attenuates incidence of mammary tumors in a rodent chemical carcinogenesis model: implications for breast cancer chemoprevention in at-risk populations. Carcinogenesis. 2012;33:2242–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Brock A, Krause S, Li H, Kowalski M, Goldberg MS, Collins JJ, et al. Silencing HoxA1 by intraductal injection of siRNA lipidoid nanoparticles prevents mammary tumor progression in mice. Sci Transl med 6:217ra2. 2014.

  40. 40.

    Yoshida T, Jin K, Song H, Park S, Huso DL, Zhang Z, Liangfeng H, Zhu C, Bruchertseifer F, Morgenstern A, Sgouros G, Sukumar S (2016) Effective treatment of ductal carcinoma in situ with a HER-2- targeted alpha-particle emitting radionuclide in a preclinical model of human breast cancer. Oncotarget 7:33306-33315. Doi:

  41. 41.

    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. 2019;40:903–13.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    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 

  43. 43.

    Zhang B, Love SM, Chen G, Wang J, Gao J, Xu X, Wang Z, Wang X (2014) The safety parameters of the study on intraductal cytotoxic agent delivery to the breast before mastectomy. Chin J Cancer Res 0:579–587.

  44. 44.

    Love SM, Zhang W, Gordon EJ, Rao J, Yang H, Li J, et al. A feasibility study of the intraductal administration of chemotherapy. Cancer Prev Res (Phila). 2013;6:51–8.

    CAS  Article  Google Scholar 

  45. 45.

    Chithrani BD, Stewart J, Allen C, Jaffray DA. Intracellular uptake, transport, and processing of nanostructures in cancer cells. Nanomedicine. 2009;5:118–27.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Chariou PL, Lee KL, Wen AM, Gulati NM, Stewart PL, Steinmetz NF. Detection and imaging of aggressive cancer cells using an epidermal growth factor receptor (EGFR)-targeted filamentous plant virus-based nanoparticle. Bioconjug Chem. 2015;26:262–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Wu D, Si M, Xue HY, Wong HL. Nanomedicine applications in the treatment of breast cancer: current state of the art. Int J Nanomedicine. 2017;12:5879–92.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Zamboni WC, Torchilin V, Patri AK, Hrkach J, Stern S, Lee R, et al. Best practices in cancer nanotechnology: perspective from NCI nanotechnology alliance. Clin Cancer Res. 2012;18:3229–41.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. 2017;17:20–37.

    CAS  Article  Google Scholar 

  50. 50.

    Sharma S, Kotamraju VR, Mölder T, Tobi A, Teesalu T, Ruoslahti E. Tumor-penetrating Nanosystem strongly suppresses breast tumor growth. Nano Lett. 2017;17:1356–64.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Alves Rico SR, Abbasi AZ, Ribeiro G, Ahmed T, Wu XY, de Oliveira SD. Diruthenium(ii,iii) metallodrugs of ibuprofen and naproxen encapsulated in intravenously injectable polymer-lipid nanoparticles exhibit enhanced activity against breast and prostate cancer cells. Nanoscale. 2017;9:10701–14.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Wang LW, Peng CW, Chen C, Li Y. Quantum dots-based tissue and in vivo imaging in breast cancer researches: current status and future perspectives. Breast Cancer Res Treat. 2015;151:7–17.

    Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Chu KF, Dupuy DE. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat Rev Cancer. 2014;14:199–208.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Hare JI, Lammers T, Ashford MB, Puri S, Storm G, Barry ST. Challenges and strategies in anti-cancer nanomedicine development: an industry perspective. Adv Drug Deliv Rev. 2017;108:25–38.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    D'Mello SR, Cruz CN, Chen ML, Kapoor M, Lee SL, Tyner KM. The evolving landscape of drug products containing nanomaterials in the United States. Nat Nanotechnol. 2017;12:523–9.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Zheng HM, Chen C, Wu XH, Chen J, Sun S, Sun JZ, et al. Quantum dot-based in situ simultaneous molecular imaging and quantitative analysis of EGFR and collagen IV and identification of their prognostic value in triple-negative breast cancer. Tumour Biol. 2016;37:2509–18.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Lv C, Lin Y, Liu AA, Hong ZY, Wen L, Zhang Z, et al. Labeling viral envelope lipids with quantum dots by harnessing the biotinylated lipid-self-inserted cellular membrane. Biomaterials. 2016;106:69–77.

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    Xu H, Chen C, He Y, Tang HW, Zhang ZL, Li Y, et al. Analysis of cancer marker in tissues with Hadamard transform fluorescence spectral microscopic imaging. J Fluoresc. 2015;25:397–402.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Hong ZY, Lv C, Liu AA, Liu SL, Sun EZ, Zhang ZL, et al. Clicking hydrazine and aldehyde: the way to labeling of viruses with quantum dots. ACS Nano. 2015;9:11750–60.

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Chen G, Zhu JY, Zhang ZL, Zhang W, Ren JG, Wu M, et al. Transformation of cell-derived microparticles into quantum-dot-labeled nanovectors for antitumor siRNA delivery. Angew Chem Int Ed Engl. 2015;54:1036–40.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Sun JZ, Chen C, Jiang G, Tian WQ, Li Y, Sun SR. Quantum dot-based immunofluorescent imaging of Ki67 and identification of prognostic value in HER2-positive (non-luminal) breast cancer. Int J Nanomedicine. 2014;9:1339–46.

    Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Chen C, Yuan JP, Wei W, Tu Y, Yao F, Yang XQ, et al. Subtype classification for prediction of prognosis of breast cancer from a biomarker panel: correlations and indications. Int J Nanomedicine. 2014;9:1039–48.

    Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Migotto A, Carvalho V, Salata GC, da Silva F, Yan C, Ishida K, et al. Multifunctional nanoemulsions for intraductal delivery as a new platform for local treatment of breast cancer. Drug Deliv. 2018;25:654–67.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Page DL, Dupont WD, Rogers LW, Landenberger M. Intraductal carcinoma of the breast: follow-up after biopsy only. Cancer. 1982;49:751–8.<751::aid-cncr2820490426>;2-y.

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Page DL, Dupont WD, Rogers LW, Jensen RA, Schuyler PA. Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer. 1995;76:1197–200.<1197::aid-cncr2820760715>;2-0.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Sanders ME, Schuyler PA, Dupont WD, Page DL. The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. Cancer. 2005;103:2481–4.

    Article  PubMed  Google Scholar 

  67. 67.

    Eusebi V, Feudale E, Foschini MP, Micheli A, Conti A, Riva C, et al. Long-term follow-up of in situ carcinoma of the breast. Semin Diagn Pathol. 1994;11:223–35.

    CAS  PubMed  Google Scholar 

  68. 68.

    Collins LC, Tamimi RM, Baer HJ, Connolly JL, Colditz GA, Schnitt SJ. Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy: results from the Nurses' health study. Cancer. 2005;103:1778–84.

    Article  PubMed  Google Scholar 

  69. 69.

    Erbas B, Provenzano E, Armes J, Gertig D. The natural history of ductal carcinoma in situ of the breast: a review. Breast Cancer Res Treat. 2006;97:135–44.

    Article  PubMed  Google Scholar 

  70. 70.

    Poller DN, Silverstein MJ, Galea M, Locker AP, Elston CW, Blamey RW, et al. Ideas in pathology. Ductal carcinoma in situ of the breast: a proposal for a new simplified histological classification association between cellular proliferation and c-erbB-2 protein expression. Mod Pathol. 1994;7:257–62.

    CAS  PubMed  Google Scholar 

  71. 71.

    Holland R, Peterse JL, Millis RR, Eusebi V, Faverly D, van de Vijver MJ, et al. Ductal carcinoma in situ: a proposal for a new classification. Semin Diagn Pathol. 1994;11:167–80.

    CAS  PubMed  Google Scholar 

  72. 72.

    Lagios MD, Margolin FR, Westdahl PR, Rose MR. Mammographically detected duct carcinoma in situ. Frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence Cancer. 1989;63:618–24.<618::aid-cncr2820630403>;2-j.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Pinder SE, Duggan C, Ellis IO, Cuzick J, Forbes JF, Bishop H, Fentiman IS, George WD, UK Coordinating Committee on Cancer Research (UKCCCR) Ductal Carcinoma In Situ (DCIS) Working Party (2010) A new pathological system for grading DCIS with improved prediction of local recurrence: results from the UKCCCR/ANZ DCIS trial. Br J Cancer 103:94–100. doi:

  74. 74.

    Simpson PT, Gale T, Reis-Filho JS, Jones C, Parry S, Sloane JP, et al. Columnar cell lesions of the breast: the missing link in breast cancer progression? A morphological and molecular analysis. Am J Surg Pathol. 2005;29:734–46.

    Article  PubMed  Google Scholar 

  75. 75.

    Betsill WL Jr, Rosen PP, Lieberman PH, Robbins GF. Intraductal carcinoma. Long-term follow-up after treatment by biopsy alone JAMA. 1978;239:1863–7.

    Article  PubMed  Google Scholar 

  76. 76.

    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. 1996;14:754–63.

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Mardekian SK, Bombonati A, Palazzo JP. Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions. Hum Pathol. 2016;49:114–23.

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Pinder SE. Ductal carcinoma in situ (DCIS): pathological features, differential diagnosis, prognostic factors and specimen evaluation. Mod Pathol. 2010;23(Suppl 2):S8–13.

    Article  PubMed  Google Scholar 

  79. 79.

    Flanagan M, Love S, Hwang ES. Status of Intraductal therapy for ductal carcinoma in situ. Curr Breast Cancer Rep. 2010;2:75–82.

    Article  PubMed  PubMed Central  Google Scholar 

  80. 80.

    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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Tekedereli I, Alpay SN, Akar U, Yuca E, Ayugo-Rodriguez C, Han HD, et al. Therapeutic silencing of Bcl-2 by systemically administered siRNA Nanotherapeutics inhibits tumor growth by autophagy and apoptosis and enhances the efficacy of chemotherapy in Orthotopic Xenograft models of ER (−) and ER (+) breast Cancer. Mol Ther Nucleic Acids. 2013;2:e121.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013;21:185–91.

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Aliabadi HM, Maranchuk R, Kucharski C, Mahdipoor P, Hugh J, Uludağ H. Effective response of doxorubicin-sensitive and -resistant breast cancer cells to combinational siRNA therapy. J Control Release. 2013;172:219–28.

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Kronski E, Fiori ME, Barbieri O, Astigiano S, Mirisola V, Killian PH, et al. miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and −2. Mol Oncol. 2014;8:581–95.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Calaf GM, Ponce-Cusi R, Carrión F. Curcumin and paclitaxel induce cell death in breast cancer cell lines. Oncol Rep. 2018;40:2381–8.

    CAS  Article  PubMed  Google Scholar 

  86. 86.

    Quispe-Soto ET, Calaf GM. Effect of curcumin and paclitaxel on breast carcinogenesis. Int J Oncol. 2016;49:2569–77.

    CAS  Article  PubMed  Google Scholar 

  87. 87.

    Carvalho V, Migotto A, Giacone DV, de Lemos DP, Zanoni TB, Maria-Engler SS, et al. Co-encapsulation of paclitaxel and C6 ceramide in tributyrin-containing nanocarriers improve co-localization in the skin and potentiate cytotoxic effects in 2D and 3D models. Eur J Pharm Sci. 2017;109:131–43.

    CAS  Article  PubMed  Google Scholar 

  88. 88.

    Fraguas-Sánchez AI, Martín-Sabroso C, Fernández-Carballido A, Torres-Suárez AI. Current status of nanomedicine in the chemotherapy of breast cancer. Cancer Chemother Pharmacol. 2019;84:689–706.

    Article  PubMed  Google Scholar 

  89. 89.

    Leshem Y, O'Brien J, Liu X, Bera TK, Terabe M, Berzofsky JA, et al. Combining local Immunotoxins targeting Mesothelin with CTLA-4 blockade synergistically eradicates murine Cancer by promoting anticancer immunity. Cancer Immunol Res. 2017;5:685–94.

    CAS  Article  Google Scholar 

  90. 90.

    Batra JK, Jinno Y, Chaudhary VK, Kondo T, Willingham MC, FitzGerald DJ, et al. Antitumor activity in mice of an immunotoxin made with anti-transferrin receptor and a recombinant form of Pseudomonas exotoxin. Proc Natl Acad Sci U S A. 1989;86:8545–9.

    CAS  Article  Google Scholar 

  91. 91.

    Chun YS, Yoshida T, Mori T, Huso DL, Zhang Z, Stearns V, et al. Intraductally administered pegylated liposomal doxorubicin reduces mammary stem cell function in the mammary gland but in the long term, induces malignant tumors. Breast Cancer Res Treat. 2012;135:201–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Elsarraj HS, Hong Y, Valdez KE, Michaels W, Hook M, Smith WP, et al. Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion. Breast Cancer Res. 2015;17:128.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Chen C, Peng J, Sun SR, Peng CW, Li Y, Pang DW. Tapping the potential of quantum dots for personalized oncology: current status and future perspectives. Nanomedicine (Lond). 2012;7:411–28.

    CAS  Article  Google Scholar 

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The datasets used and/or analyzed during the current study are available from the corresponding author for reasonable requests.


This research was supported by grants from the Fundamental Research Funds for the Central Universities (2042019kf0229), the Science and Technology Major Project of Hubei Province (Next-Generation AI Technologies) (2019AEA170), the National Natural Science Foundation of China (81802895) and by the Fetting Fund.

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Xin-Wen Kuang and Zhi-Hong Sun collected and analyzed relevant literature. Jian-Hua Liu and Xin-Wen Kuang drafted the manuscript. Chuang Chen, Saraswati Sukumar and Sheng-Rong Sun critically revised the manuscript for content. All authors read and approved the final manuscript.

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Correspondence to Chuang Chen.

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Kuang, X., Liu, J., Sun, Z. et al. Intraductal Therapy in Breast Cancer: Current Status and Future Prospective. J Mammary Gland Biol Neoplasia (2020).

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  • Breast cancer
  • Intraductal therapy
  • Minimally invasive
  • Personalized therapy
  • Nanomedicine
  • Ductal carcinoma in situ