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The clinical significance of HER2 expression in DCIS

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Abstract

HER2 is an established prognostic and predictive marker for patients with invasive breast cancer. The clinical and biological significance of HER2 overexpression in patients with ductal carcinoma in situ (DCIS) remains poorly defined. DCIS is a heterogeneous disease and some patients with DCIS will not progress to invasive breast cancer. However, clinically significant recurrence rates have been reported after breast-conserving surgery for DCIS and approximately half of these cases will be life-threatening invasive recurrences. Since the incidence of DCIS is rising due to the widespread use of screening mammography, there is robust interest in selecting high-risk DCIS patients that may benefit from adjuvant therapies. Molecular prognostic and predictive models in early invasive breast cancer help clinicians identify patients that will benefit from chemotherapy. Molecular subtyping and profiling could also be useful in treating DCIS patients. According to current practice guidelines, HER2 testing is not recommended in DCIS patients. Nevertheless, evidence suggests that HER2-positive DCIS cases may be associated with adverse clinicopathological parameters and increased recurrence rates. This review summarizes the existing body of evidence linking HER2 expression and ipsilateral breast cancer recurrence in DCIS. HER2, as well as its correlation with other clinicopathological markers might be a useful prognostic and predictive marker, helping clinical decision-making in DCIS patients.

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References

  1. DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, Jemal A, Siegel RL. Breast cancer statistics, 2019. CA Cancer J Clin. 2019;69(6):438–51. https://doi.org/10.3322/caac.21583.

    Article  Google Scholar 

  2. American Cancer Society. How Common Is Breast Cancer? Available at: https://www.cancer.org/cancer/breast-cancer/about/how-common-is-breast-cancer.html (Accessed on June 27, 2022)

  3. Lagios MD. Duct carcinoma in situ: a personal perspective. Breast J. 2020;26(6):1132–7. https://doi.org/10.1111/tbj.13860.

    Article  Google Scholar 

  4. van Seijen M, Lips EH, Thompson AM, Nik-Zainal S, Futreal A, Hwang ES, Verschuur E, Lane J, Jonkers J, Rea DW, Wesseling J. PRECISION team. Ductal carcinoma in situ: to treat or not to treat, that is the question. Br J Cancer. 2019;121(4):285–92. https://doi.org/10.1038/s41416-019-0478-6.

    Article  Google Scholar 

  5. Solin LJ. Management of ductal carcinoma in situ (DCIS) of the breast: present approaches and future directions. Curr Oncol Rep. 2019;21(4):33. https://doi.org/10.1007/s11912-019-0777-3.

    Article  Google Scholar 

  6. Solin LJ, Gray R, Baehner FL, Butler SM, Hughes LL, Yoshizawa C, Cherbavaz DB, Shak S, Page DL, Sledge GW Jr, Davidson NE, Ingle JN, Perez EA, Wood WC, Sparano JA, Badve S. A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2013;105(10):701–10. https://doi.org/10.1093/jnci/djt067.

    Article  CAS  Google Scholar 

  7. Bremer T, Whitworth PW, Patel R, Savala J, Barry T, Lyle S, Leesman G, Linke SP, Jirström K, Zhou W, Amini RM, Wärnberg F. A biological signature for breast ductal carcinoma in situ to predict radiotherapy benefit and assess recurrence risk. Clin Cancer Res. 2018;24(23):5895–901. https://doi.org/10.1158/1078-0432.CCR-18-0842.

    Article  Google Scholar 

  8. Gradishar WJ, Moran MS, Abraham J, Aft R, Agnese D, Allison KH, Anderson B, Burstein HJ, Chew H, Dang C, Elias AD, Giordano SH, Goetz MP, Goldstein LJ, Hurvitz SA, Isakoff SJ, Jankowitz RC, Javid SH, Krishnamurthy J, Leitch M, Lyons J, Mortimer J, Patel SA, Pierce LJ, Rosenberger LH, Rugo HS, Sitapati A, Smith KL, Smith ML, Soliman H, StringerReasor EM, Telli ML, Ward JH, Wisinski KB, Young JS, Burns J, Kumar R. Breast cancer version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022;20(6):691–722. https://doi.org/10.6004/jnccn.2022.0030.

    Article  Google Scholar 

  9. Solek J, Chrzanowski J, Cieslak A, Zielinska A, Piasecka D, Braun M, Sadej R, Romanska HM. Subtype-specific tumour immune microenvironment in risk of recurrence of ductal carcinoma in situ: prognostic value of HER2. Biomedicines. 2022;10(5):1061. https://doi.org/10.3390/biomedicines10051061.

    Article  CAS  Google Scholar 

  10. Pruneri G, Lazzeroni M, Bagnardi V, Tiburzio GB, Rotmensz N, DeCensi A, Guerrieri-Gonzaga A, Vingiani A, Curigliano G, Zurrida S, Bassi F, Salgado R, Van den Eynden G, Loi S, Denkert C, Bonanni B, Viale G. The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast. Ann Oncol. 2017;28(2):321–8. https://doi.org/10.1093/annonc/mdw623.

    Article  CAS  Google Scholar 

  11. Miligy I, Mohan P, Gaber A, Aleskandarany MA, Nolan CC, Diez-Rodriguez M, Mukherjee A, Chapman C, Ellis IO, Green AR, Rakha EA. Prognostic significance of tumour infiltrating B lymphocytes in breast ductal carcinoma in situ. Histopathology. 2017;71(2):258–68. https://doi.org/10.1111/his.13217.

    Article  Google Scholar 

  12. Silverstein MJ, Lagios MD. Choosing treatment for patients with ductal Carcinoma in situ: fine tuning the University of Southern California/Van Nuys Prognostic Index. J Natl Cancer Inst Monogr. 2010;2010(41):193–6. https://doi.org/10.1093/jncimonographs/lgq040.

    Article  Google Scholar 

  13. Rudloff U, Jacks LM, Goldberg JI, Wynveen CA, Brogi E, Patil S, Van Zee KJ. Nomogram for predicting the risk of local recurrence after breast-conserving surgery for ductal carcinoma in situ. J Clin Oncol. 2010;28(23):3762–9. https://doi.org/10.1200/JCO.2009.26.8847.

    Article  Google Scholar 

  14. Punglia RS, Jiang W, Lipsitz SR, Hughes ME, Schnitt SJ, Hassett MJ, Nekhlyudov L, Achacoso N, Edge S, Javid SH, Niland JC, Theriault RL, Wong YN, Habel LA. Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery. Breast Cancer Res Treat. 2018;167(3):751–9. https://doi.org/10.1007/s10549-017-4553-5.

    Article  CAS  Google Scholar 

  15. Thorat MA, Levey PM, Jones JL, Pinder SE, Bundred NJ, Fentiman IS, Cuzick J. Prognostic and predictive value of her2 expression in ductal carcinoma in situ: results from the UK/ANZ DCIS Randomized trial. Clin Cancer Res. 2021;27(19):5317–24. https://doi.org/10.1158/1078-0432.CCR-21-1239.

    Article  CAS  Google Scholar 

  16. Borgquist S, Zhou W, Jirström K, Amini RM, Sollie T, Sørlie T, Blomqvist C, Butt S, Wärnberg F. The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study. BMC Cancer. 2015;15:468. https://doi.org/10.1186/s12885-015-1479-3.

    Article  CAS  Google Scholar 

  17. O’Keefe TJ, Blair SL, Hosseini A, Harismendy O, Wallace AM. HER2-overexpressing ductal carcinoma in situ associated with increased risk of ipsilateral invasive recurrence, receptor discordance with recurrence. Cancer Prev Res (Phila). 2020;13(9):761–72. https://doi.org/10.1158/1940-6207.CAPR-20-0024.

    Article  Google Scholar 

  18. Noh JM, Lee J, Choi DH, Cho EY, Huh SJ, Park W, Nam SJ, Lee JE, Kil WH. HER-2 overexpression is not associated with increased ipsilateral breast tumor recurrence in DCIS treated with breast-conserving surgery followed by radiotherapy. Breast. 2013;22(5):894–7. https://doi.org/10.1016/j.breast.2013.04.001.

    Article  Google Scholar 

  19. Miligy IM, Gorringe KL, Lee AHS, Ellis IO, Green AR, Rakha EA. The clinical and biological significance of HER2 over-expression in breast ductal carcinoma in situ: a large study from a single institution. Br J Cancer. 2019;120(11):1075–82. https://doi.org/10.1038/s41416-019-0436-3.

    Article  CAS  Google Scholar 

  20. Curigliano G, Disalvatore D, Esposito A, Pruneri G, Lazzeroni M, Guerrieri-Gonzaga A, Luini A, Orecchia R, Goldhirsch A, Rotmensz N, Bonanni B, Viale G. Risk of subsequent in situ and invasive breast cancer in human epidermal growth factor receptor 2-positive ductal carcinoma in situ. Ann Oncol. 2015;26(4):682–7. https://doi.org/10.1093/annonc/mdv013.

    Article  CAS  Google Scholar 

  21. Di Cesare P, Pavesi L, Villani L, Battaglia A, Da Prada GA, Riccardi A, Frascaroli M. The relationships between HER2 overexpression and DCIS characteristics. Breast J. 2017;23(3):307–14. https://doi.org/10.1111/tbj.12735.

    Article  CAS  Google Scholar 

  22. Williams KE, Barnes NLP, Cramer A, Johnson R, Cheema K, Morris J, Howe M, Bundred NJ. Molecular phenotypes of DCIS predict overall and invasive recurrence. Ann Oncol. 2015;26(5):1019–25. https://doi.org/10.1093/annonc/mdv062.

    Article  CAS  Google Scholar 

  23. Visser LL, Elshof LE, Schaapveld M, van de Vijver K, Groen EJ, Almekinders MM, Bierman C, van Leeuwen FE, Rutgers EJ, Schmidt MK, Lips EH, Wesseling J. Clinicopathological risk factors for an invasive breast cancer recurrence after ductal carcinoma in situ-a nested case-control study. Clin Cancer Res. 2018;24(15):3593–601. https://doi.org/10.1158/1078-0432.CCR-18-0201.

    Article  CAS  Google Scholar 

  24. Nofech-Mozes S, Spayne J, Rakovitch E, Kahn HJ, Seth A, Pignol JP, Lickley L, Paszat L, Hanna W. Biological markers predictive of invasive recurrence in DCIS. Clin Med Oncol. 2008;2:7–18.

    CAS  Google Scholar 

  25. Davis JE, Nemesure B, Mehmood S, Nayi V, Burke S, Brzostek SR, Singh M. Her2 and Ki67 biomarkers predict recurrence of ductal carcinoma in situ. Appl Immunohistochem Mol Morphol. 2016;24(1):20–5. https://doi.org/10.1097/PAI.0000000000000223.

    Article  CAS  Google Scholar 

  26. Gong DH, Ge JY, Chen YY, Ding KF, Yu KD. HER2 overexpression in ductal carcinoma in situ is associated with ipsilateral breast cancer recurrence after conservative surgery. Transl Cancer Res. 2020;9(6):3787–93. https://doi.org/10.21037/tcr-20-1481.

    Article  CAS  Google Scholar 

  27. Kim K, Kim JH, Kim YB, Suh CO, Shin KH, Kim JH, Kim TH, Jung SY, Choi DH, Park W, Ahn SD, Kim SS, Yea JW, Kang MK, Kim DW, Kim YJ. Selective radiation therapy for ductal carcinoma in situ following breast-conserving surgery according to age and margin width: Korean Radiation Oncology Group 11–04 and 16–02 Studies. J Breast Cancer. 2017;20(4):327–32. https://doi.org/10.4048/jbc.2017.20.4.327.

    Article  Google Scholar 

  28. Kim JH, Choi DH, Park W, Ahn SD, Kim SS, Ha SW, Kim K, Kim YB, Yea JW, Kang MK, Shin KH, Kim DW, Lee JH, Suh CO. Influence of boost radiotherapy in patients with ductal carcinoma in situ breast cancer: a multicenter, retrospective study in Korea (KROG 11–04). Breast Cancer Res Treat. 2014;146(2):341–5. https://doi.org/10.1007/s10549-014-3025-4.

    Article  CAS  Google Scholar 

  29. Leonardi MC, Corrao G, Frassoni S, Vingiani A, Dicuonzo S, Lazzeroni M, Fodor C, Morra A, Gerardi MA, Rojas DP, Dell’Acqua V, Marvaso G, Bassi FD, Galimberti VE, Veronesi P, Miglietta E, Cattani F, Zurrida S, Bagnardi V, Viale G, Orecchia R, Jereczek-Fossa BA. Ductal carcinoma in situ and intraoperative partial breast irradiation: who are the best candidates? Long-term outcome of a single institution series. Radiother Oncol. 2019;133:68–76. https://doi.org/10.1016/j.radonc.2018.12.030.

    Article  Google Scholar 

  30. Toss A, Palazzo J, Berger A, Guiles F, Sendecki JA, Simone N, Anne R, Avery T, Jaslow R, Lazar M, Tsangaris T, Cristofanilli M. Clinical-pathological features and treatment modalities associated with recurrence in DCIS and micro-invasive carcinoma: who to treat more and who to treat less. Breast. 2016;29:223–30. https://doi.org/10.1016/j.breast.2016.07.023.

    Article  Google Scholar 

  31. Poulakaki N, Makris GM, Battista MJ, Böhm D, Petraki K, Bafaloukos D, Sergentanis TN, Siristatidis C, Chrelias C, Papantoniou N. Hormonal receptor status, Ki-67 and HER2 expression: Prognostic value in the recurrence of ductal carcinoma in situ of the breast? Breast. 2016;25:57–61. https://doi.org/10.1016/j.breast.2015.10.007.

    Article  Google Scholar 

  32. Kim JY, Park K, Kang G, Kim HJ, Gwak G, Shin YJ. Predictors of recurrent ductal carcinoma in situ after breast-conserving surgery. J Breast Cancer. 2016;19(2):185–90. https://doi.org/10.4048/jbc.2016.19.2.185.

    Article  Google Scholar 

  33. Ozkaya Akagunduz O, Ergen A, Erpolat P, et al. Local recurrence outcomes after breast conserving surgery and adjuvant radiotherapy in ductal carcinoma in situ of the breast and a comparison with ECOG E5194 study. Breast. 2018;42:10–4. https://doi.org/10.1016/j.breast.2018.08.094.

    Article  Google Scholar 

  34. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52. https://doi.org/10.1038/35021093.

    Article  CAS  Google Scholar 

  35. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ. Panel members. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer. Ann Oncol. 2013;24(9):2206–23. https://doi.org/10.1093/annonc/mdt303.

    Article  CAS  Google Scholar 

  36. Tsang JYS, Tse GM. Molecular classification of breast cancer. Adv Anat Pathol. 2020;27(1):27–35. https://doi.org/10.1097/PAP.0000000000000232.

    Article  CAS  Google Scholar 

  37. Sadeghalvad M, Mohammadi-Motlagh HR, Rezaei N. Immune microenvironment in different molecular subtypes of ductal breast carcinoma. Breast Cancer Res Treat. 2021;185(2):261–79. https://doi.org/10.1007/s10549-020-05954-2.

    Article  CAS  Google Scholar 

  38. Yang L, Shen M, Qiu Y, Tang T, Bu H. Molecular subtyping reveals uniqueness of prognosis in breast ductal carcinoma in situ patients with lumpectomy. Breast. 2022;64:1–6. https://doi.org/10.1016/j.breast.2022.03.019.

    Article  Google Scholar 

  39. Yang Y, Zhao X, Wang X, Jin K, Luo J, Yang Z, Mei X, Ma J, Shao Z, Zhang Z, Chen X, Guo X, Yu X. Molecular subtypes predict second breast events of ductal carcinoma in situ after breast-conserving surgery. Cancer Med. 2022. https://doi.org/10.1002/cam4.4651.

    Article  Google Scholar 

  40. Wu ZY, Kim HJ, Lee J, et al. Recurrence outcomes after Nipple-Sparing mastectomy and immediate breast reconstruction in patients with pure ductal carcinoma in situ. Ann Surg Oncol. 2020;27(5):1627–35. https://doi.org/10.1245/s10434-019-08184-z.

    Article  Google Scholar 

  41. Knopfelmacher A, Fox J, Lo Y, Shapiro N, Fineberg S. Correlation of histopathologic features of ductal carcinoma in situ of the breast with the oncotype DX DCIS score. Mod Pathol. 2015;28(9):1167–73. https://doi.org/10.1038/modpathol.2015.79.

    Article  CAS  Google Scholar 

  42. Gennaro M, De Santis MC, Mariani L, Lo Vullo S, Cappelletti V, Agresti R, Cortinovis U, Paolini B, Di Cosimo S, Carcangiu ML, Daidone MG, Lozza L. Ten-year results of applying an original scoring system for addressing adjuvant therapy use after breast-conserving surgery for ductal carcinoma in situ of the breast. Breast. 2017;35:63–8. https://doi.org/10.1016/j.breast.2017.06.010.

    Article  Google Scholar 

  43. Siziopikou KP, Anderson SJ, Cobleigh MA, Julian TB, Arthur DW, Zheng P, Mamounas EP, Pajon ER, Behrens RJ, Eakle JF, Leasure NC, Atkins JN, Polikoff JA, Seay TE, McCaskill-Stevens WJ, Rabinovitch R, Costantino JP, Wolmark N. Preliminary results of centralized HER2 testing in ductal carcinoma in situ (DCIS): NSABP B-43. Breast Cancer Res Treat. 2013;142(2):415–21. https://doi.org/10.1007/s10549-013-2755-z.

    Article  CAS  Google Scholar 

  44. Kuerer HM, Buzdar AU, Mittendorf EA, Esteva FJ, Lucci A, Vence LM, Radvanyi L, Meric-Bernstam F, Hunt KK, Symmans WF. Biologic and immunologic effects of preoperative trastuzumab for ductal carcinoma in situ of the breast. Cancer. 2011;117(1):39–47. https://doi.org/10.1002/cncr.25399.

    Article  CAS  Google Scholar 

  45. Liang K, Lu Y, Jin W, Ang KK, Milas L, Fan Z. Sensitization of breast cancer cells to radiation by trastuzumab. Mol Cancer Ther. 2003;2(11):1113–20.

    CAS  Google Scholar 

  46. Cobleigh MA, Anderson SJ, Siziopikou KP, Arthur DW, Rabinovitch R, Julian TB, Parda DS, Seaward SA, Carter DL, Lyons JA, Dillmon MS, Magrinat GC, Kavadi VS, Zibelli AM, Tiriveedhi L, Hill ML, Melnik MK, Beriwal S, Mamounas EP, Wolmark N. Comparison of radiation with or without concurrent trastuzumab for HER2-positive ductal carcinoma in situ resected by lumpectomy: a phase III clinical trial. J Clin Oncol. 2021;39(21):2367–74. https://doi.org/10.1200/JCO.20.02824.

    Article  CAS  Google Scholar 

  47. Lewis GD, Haque W, Farach A, Hatch SS, Butler EB, Niravath PA, Schwartz MR, Bonefas E, Teh BS. The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast. Rep Pract Oncol Radiother. 2021;26(2):179–87. https://doi.org/10.5603/RPOR.a2021.0026.

    Article  Google Scholar 

  48. Ahn S, Woo JW, Lee K, Park SY. HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation. J Pathol Transl Med. 2020;54(1):34–44. https://doi.org/10.4132/jptm.2019.11.03.

    Article  Google Scholar 

  49. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF. American Society of Clinical Oncology; College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25(1):118–45. https://doi.org/10.1200/JCO.2006.09.2775.

    Article  CAS  Google Scholar 

  50. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF. American Society of Clinical Oncology; College of American Pathologists. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013. https://doi.org/10.1200/JCO.2013.50.9984.

    Article  Google Scholar 

  51. Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, Bilous M, Ellis IO, Fitzgibbons P, Hanna W, Jenkins RB, Press MF, Spears PA, Vance GH, Viale G, McShane LM, Dowsett M. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Arch Pathol Lab Med. 2018;142(11):1364–82. https://doi.org/10.5858/arpa.2018-0902-SA.

    Article  Google Scholar 

  52. Marchiò C, Annaratone L, Marques A, Casorzo L, Berrino E, Sapino A. Evolving concepts in HER2 evaluation in breast cancer: heterogeneity, HER2-low carcinomas and beyond. Semin Cancer Biol. 2021;72:123–35. https://doi.org/10.1016/j.semcancer.2020.02.016.

    Article  CAS  Google Scholar 

  53. Lari SA, Kuerer HM. Biological markers in DCIS and risk of breast recurrence: a systematic review. J Cancer. 2011;2:232–61. https://doi.org/10.7150/jca.2.232.

    Article  Google Scholar 

  54. Gorringe KL, Fox SB. Ductal carcinoma in situ biology, biomarkers, and diagnosis. Front Oncol. 2017;7:248. https://doi.org/10.3389/fonc.2017.00248.

    Article  Google Scholar 

  55. Visser LL, Groen EJ, van Leeuwen FE, Lips EH, Schmidt MK, Wesseling J. Predictors of an invasive breast cancer recurrence after DCIS: a systematic review and meta-analyses. Cancer Epidemiol Biomarkers Prev. 2019;28(5):835–45. https://doi.org/10.1158/1055-9965.EPI-18-0976.

    Article  CAS  Google Scholar 

  56. Rakovitch E, Nofech-Mozes S, Hanna W, Narod S, Thiruchelvam D, Saskin R, Spayne J, Taylor C, Paszat L. HER2/neu and Ki-67 expression predict non-invasive recurrence following breast-conserving therapy for ductal carcinoma in situ. Br J Cancer. 2012;106(6):1160–5. https://doi.org/10.1038/bjc.2012.41.

    Article  CAS  Google Scholar 

  57. Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, Sanchez H, Jimenez C, Stewart K, Chew K, Ljung BM, Tlsty TD. Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst. 2010;102(9):627–37. https://doi.org/10.1093/jnci/djq101.

    Article  CAS  Google Scholar 

  58. Ozaki T, Nakagawara A. Role of p53 in Cell DEATH AND HUMAN CANCERS. Cancers (Basel). 2011;3(1):994–1013. https://doi.org/10.3390/cancers3010994.

    Article  CAS  Google Scholar 

  59. de Roos MA, de Bock GH, de Vries J, van der Vegt B, Wesseling J. p53 overexpression is a predictor of local recurrence after treatment for both in situ and invasive ductal carcinoma of the breast. J Surg Res. 2007;140(1):109–14. https://doi.org/10.1016/j.jss.2006.10.045.

    Article  CAS  Google Scholar 

  60. Takahashi S, Thike AA, Koh VCY, Sasano H, Tan PH. Triple-negative and HER2 positive ductal carcinoma in situ of the breast: characteristics, behavior, and biomarker profile. Virchows Arch. 2018;473(3):275–83. https://doi.org/10.1007/s00428-018-2416-z.

    Article  CAS  Google Scholar 

  61. Abba MC, Gong T, Lu Y, Lee J, Zhong Y, Lacunza E, Butti M, Takata Y, Gaddis S, Shen J, Estecio MR, Sahin AA, Aldaz CM. A molecular portrait of high-grade ductal carcinoma in situ. Cancer Res. 2015;75(18):3980–90. https://doi.org/10.1158/0008-5472.CAN-15-0506.

    Article  CAS  Google Scholar 

  62. Vincent-Salomon A, Lucchesi C, Gruel N, Raynal V, Pierron G, Goudefroye R, Reyal F, Radvanyi F, Salmon R, Thiery JP, Sastre-Garau X, Sigal-Zafrani B, Fourquet A, Delattre O. Breast cancer study group of the Institut Curie. Integrated genomic and transcriptomic analysis of ductal carcinoma in situ of the breast. Clin Cancer Res. 2008;14(7):1956–65. https://doi.org/10.1158/1078-0432.CCR-07-1465.

    Article  CAS  Google Scholar 

  63. Hernandez L, Wilkerson PM, Lambros MB, Campion-Flora A, Rodrigues DN, Gauthier A, Cabral C, Pawar V, Mackay A, A’Hern R, Marchiò C, Palacios J, Natrajan R, Weigelt B, Reis-Filho JS. Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection. J Pathol. 2012;227(1):42–52. https://doi.org/10.1002/path.3990.

    Article  CAS  Google Scholar 

  64. Pang JB, Savas P, Fellowes AP, Mir Arnau G, Kader T, Vedururu R, Hewitt C, Takano EA, Byrne DJ, Choong DY, Millar EK, Lee CS, O’Toole SA, Lakhani SR, Cummings MC, Mann GB, Campbell IG, Dobrovic A, Loi S, Gorringe KL, Fox SB. Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer. Mod Pathol. 2017;30(7):952–63. https://doi.org/10.1038/modpathol.2017.21.

    Article  CAS  Google Scholar 

  65. Lin CY, Vennam S, Purington N, Lin E, Varma S, Han S, Desa M, Seto T, Wang NJ, Stehr H, Troxell ML, Kurian AW, West RB. Genomic landscape of ductal carcinoma in situ and association with progression. Breast Cancer Res Treat. 2019;178(2):307–16. https://doi.org/10.1007/s10549-019-05401-x.

    Article  CAS  Google Scholar 

  66. Agahozo MC, Sieuwerts AM, Doebar SC, Verhoef EI, Beaufort CM, Ruigrok-Ritstier K, de Weerd V, Sleddens HFBM, Dinjens WNM, Martens JWM, van Deurzen CHM. PIK3CA mutations in ductal carcinoma in situ and adjacent invasive breast cancer. Endocr Relat Cancer. 2019;26(5):471–82. https://doi.org/10.1530/ERC-19-0019.

    Article  CAS  Google Scholar 

  67. Nagasawa S, Kuze Y, Maeda I, Kojima Y, Motoyoshi A, Onishi T, Iwatani T, Yokoe T, Koike J, Chosokabe M, Kubota M, Seino H, Suzuki A, Seki M, Tsuchihara K, Inoue E, Tsugawa K, Ohta T, Suzuki Y. Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast. Commun Biol. 2021;4(1):438. https://doi.org/10.1038/s42003-021-01959-9.

    Article  CAS  Google Scholar 

  68. Sakr RA, Weigelt B, Chandarlapaty S, Andrade VP, Guerini-Rocco E, Giri D, Ng CK, Cowell CF, Rosen N, Reis-Filho JS, King TA. PI3K pathway activation in high-grade ductal carcinoma in situ–implications for progression to invasive breast carcinoma. Clin Cancer Res. 2014;20(9):2326–37. https://doi.org/10.1158/1078-0432.CCR-13-2267.

    Article  CAS  Google Scholar 

  69. Sueta A, Yamamoto Y, Yamamoto-Ibusuki M, Hayashi M, Takeshita T, Yamamoto S, Iwase H. An integrative analysis of PIK3CA mutation, PTEN, and INPP4B expression in terms of trastuzumab efficacy in HER2-positive breast cancer. PLoS ONE. 2014;9(12):e116054. https://doi.org/10.1371/journal.pone.0116054.

    Article  CAS  Google Scholar 

  70. Kim JW, Lim AR, You JY, Lee JH, Song SE, Lee NK, Jung SP, Cho KR, Kim CY, Park KH. PIK3CA mutation is associated with poor response to HER2-targeted therapy in breast cancer patients. Cancer Res Treat. 2022. https://doi.org/10.4143/crt.2022.221.

    Article  Google Scholar 

  71. Chung WP, Huang WL, Lee CH, Hsu HP, Huang WL, Liu YY, Su WC. PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations. Am J Cancer Res. 2022;12(7):3067–82.

    CAS  Google Scholar 

  72. Takaku M, Grimm SA, Wade PA. GATA3 in breast cancer: tumor suppressor or oncogene? Gene Expr. 2015;16(4):163–8. https://doi.org/10.3727/105221615X14399878166113.

    Article  CAS  Google Scholar 

  73. Jeon M, You D, Bae SY, Kim SW, Nam SJ, Kim HH, Kim S, Lee JE. Dimerization of EGFR and HER2 induces breast cancer cell motility through STAT1-dependent ACTA2 induction. Oncotarget. 2016;8(31):50570–81. https://doi.org/10.18632/oncotarget.10843.

    Article  Google Scholar 

  74. Guo P, Pu T, Chen S, Qiu Y, Zhong X, Zheng H, Chen L, Bu H, Ye F. Breast cancers with EGFR and HER2 co-amplification favor distant metastasis and poor clinical outcome. Oncol Lett. 2017;14(6):6562–70. https://doi.org/10.3892/ol.2017.7051.

    Article  CAS  Google Scholar 

  75. Ciardiello F, Normanno N. HER2 signaling and resistance to the anti-EGFR monoclonal antibody cetuximab: a further step toward personalized medicine for patients with colorectal cancer. Cancer Discov. 2011;1(6):472–4. https://doi.org/10.1158/2159-8290.CD-11-0261.

    Article  CAS  Google Scholar 

  76. Steinman S, Wang J, Bourne P, Yang Q, Tang P. Expression of cytokeratin markers, ER-alpha, PR, HER-2/neu, and EGFR in pure ductal carcinoma in situ (DCIS) and DCIS with co-existing invasive ductal carcinoma (IDC) of the breast. Ann Clin Lab Sci. 2007;37(2):127–34.

    CAS  Google Scholar 

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  1. Department of General Surgery, University General Hospital of Patras, Rion, Greece

    Ioanna Akrida & Francesk Mulita

  2. Department of Anatomy-Histology-Embryology, University of Patras Medical School, 26504, Rion, Greece

    Ioanna Akrida

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Akrida, I., Mulita, F. The clinical significance of HER2 expression in DCIS. Med Oncol 40, 16 (2023). https://doi.org/10.1007/s12032-022-01876-9

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