DUKTALNI KARCINOM IN SITU: AKTUELNI DIJAGNOSTIČKI I TERAPIJSKI PRISTUPI
Sažetak
Razvoj metoda skrininga značajno je povećao učestalost dijagnostikovanja duktalnog karcinoma in situ (DCIS). Iako se odlikuje visokom stopom preživljavanja, DCIS predtsvalja klinički izazovan entitet zbog svoje biološke heterogenosti i potencijala za progresiju u invazivni duktalni karcinom (IDC). Mamografija i dalje ostaje primarna dijagnostička metoda, pri čemu su mikrokalcifikacije najčešći nalaz. Lečenje je prvenstveno hirurško – lumpektomijom ili mastektomijom, u zavisnosti od proširenosti lezije. U slučajevima poštednih operacija preporučuje se adjuvantna radioterapija radi smanjenja rizika od lokalnog recidiva, dok se hormonska terapija (tamoksifen i inhibitori aromataze) primenjuje kod hormonski pozitivnih tumora. Disekcija aksilarnih limfnih čvorova ne sprovodi se rutinski, ali može biti indikovana u slučaju mikroinvazije. U novije vreme, aktivni nadzor razmatra se kao alternativa kod pacijentkinja niskog rizika, pri čemu su savremena istraživanja fokusirana na razvoj prognostičkih faktora za precizniju stratifikaciju rizika.
Ovaj rad pruža pregled savremenih multidisciplinarnih pristupa dijagnostike i lečenja DCIS-a, zasnovanih na najnovijim saznanjima iz naučne literature.
Reference
Hophan SL, Odnokoz O, Liu H, Luo Y, Khan S, Gradishar W, et al. Ductal carcinoma in situ of breast: from molecular etiology to therapeutic management. Endocrinology. 2022;163(4):bqac027. doi: 10.1210/endocr/bqac027.
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(9):1778-84. doi: 10.1002/cncr.20979.
Strand SH, Rivero-Gutiérrez B, Houlahan KE, Seoane JA, King LM, Risom T, et al. Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts. Cancer Cell. 2022;40(12):1521-36.e7. doi: 10.1016/j.ccell.2022.10.021.
Murata T, Yoshida M, Shiino S, Watase C, Ogawa A, Shikata S, et al. Assessment of nuclear grade-based recurrence risk classification in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive high-risk early breast cancer. Breast Cancer. 2023;30(6):1054-64. doi: 10.1007/s12282-023-01500-2.
Chen J, Li Z, Han Z, Kang D, Ma J, Yi Y, et al. Prognostic value of tumor necrosis based on the evaluation of frequency in invasive breast cancer. BMC Cancer. 2023;23(1):530. doi: 10.1186/s12885-023-10943-x.
National Comprehensive Cancer Network. NCCN Guidelines. Ductal carcinoma in situ [Internet]. Available from: https://jnccn.org/view/journals/jnccn/20/6/article-p691.xml. Accessed: 2025 Apr 12.
White E, Lee CY, Kristal AR. Evaluation of the increase in breast cancer incidence in relation to mammography use. J Natl Cancer Inst. 1990;82(19):1546-52. doi: 10.1093/jnci/82.19.1546.
Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, et al. SEER cancer statistics review, 1975–2018 [Internet]. Bethesda, MD: National Cancer Institute; 2021. Available from: http://seer.cancer.gov/csr/1975_2018. Accessed: 2025 Apr 17.
Dershaw DD, Abramson A, Kinne DW. Ductal carcinoma in situ: mammographic findings and clinical implications. Radiology. 1989;170(2):411-5. doi: 10.1148/radiology.170.2.2536185.
Stomper PC, Connolly JL, Meyer JE, Harris JR. Clinically occult ductal carcinoma in situ detected with mammography: analysis of 100 cases with radiologic-pathologic correlation. Radiology. 1989;172(1):235-41. doi: 10.1148/radiology.172.1.2544922.
Paquelet JR, Hendrick RE. Lesion size inaccuracies in digital mammography. AJR Am J Roentgenol. 2010;194(1):W115-8. doi: 10.2214/AJR.09.2927.
D'Alfonso TM, Ginter PS, Shin SJ. A review of inflammatory processes of the breast with a focus on diagnosis in core biopsy samples. J Pathol Transl Med. 2015;49(4):279-87. doi: 10.4132/jptm.2015.06.11.
Fallenberg EM, Dimitrijevic L, Diekmann F, Diekmann S, Kettritz U, Poellinger A, et al. Impact of magnification views on the characterization of microcalcifications in digital mammography. Rofo. 2014;186(3):274-80. doi: 10.1055/s-0033-1350572.
Uslu H, Tosun M, Arslan AS. Non-mass enhancement of breast MRI: The comparison of benign and malignant pathological diagnosis and association of internal enhancement pattern and distribution with breast cancer molecular sub-types. Acta Medica Nicomedia. 2022;5(3):165–71. doi: 10.5336/actamednicommedia.2022-1128352.
Endrikat J, Schmidt G, Haverstock D, Weber O, Trnkova ZJ, Barkhausen J. Sensitivity of contrast-enhanced breast MRI vs X-ray mammography based on cancer histology, tumor grading, receptor status, and molecular subtype: a supplemental analysis of 2 large phase III studies. Breast Cancer (Auckl). 2022;16:11782234221092155. doi: 10.1177/11782234221092155.
Amitai Y, Menes TS, Scaranelo A, Fleming R, Kulkarni S, Ghai S, et al. The characteristics associated with upgrade on surgical pathology of conventional imaging occult DCIS diagnosed by MRI. Breast Cancer Res Treat. 2021;190(2):317-27. doi: 10.1007/s10549-021-06372-8.
Boné B, Aspelin P, Bronge L, Isberg B, Perbeck L, Veress B. Sensitivity and specificity of MR mammography with histopathological correlation in 250 breasts. Acta Radiol. 1996;37(2):208-13. doi: 10.1177/02841851960371P143.
Yao Y, Mou F, Kong J, Liu X. Kinetic heterogeneity improves the specificity of dynamic enhanced MRI in differentiating benign and malignant breast tumours. Acad Radiol. 2024;31(3):812-21. doi: 10.1016/j.acra.2023.10.006.
Cha H, Chang YW, Lee EJ, Hwang JY, Kim HJ, Lee EH, et al. Ultrasonographic features of pure ductal carcinoma in situ of the breast: correlations with pathologic features and biological markers. Ultrasonography. 2018;37(4):307-14. doi: 10.14366/usg.17039.
Yuan WH, Hsu HC, Chen YY, Wu CH. Supplemental breast cancer-screening ultrasonography in women with dense breasts: a systematic review and meta-analysis. Br J Cancer. 2020;123(4):673-88. doi: 10.1038/s41416-020-0928-1.
Kettritz U. Modern concepts of ductal carcinoma in situ (DCIS) and its diagnosis through percutaneous biopsy. Eur Radiol. 2008;18(2):343-50. doi: 10.1007/s00330-007-0753-4.
Alexander N, Viljoen I, Lucas S. Stereotactic breast biopsies: radiological-pathological concordance in a South African referral unit. SA J Radiol. 2022;26(1):2463. doi: 10.4102/sajr.v26i1.2463.
Davey MG, O'Flaherty C, Cleere EF, Nohilly A, Phelan J, Ronane E, et al. Sentinel lymph node biopsy in patients with ductal carcinoma in situ: systematic review and meta-analysis. BJS Open. 2022;6(2):zrac022. doi: 10.1093/bjsopen/zrac022.
Zdravkovic D, Loboda B, Gojgic M, Toskovic B. Techniques for sentinel lymph node biopsy in breast cancer patients. Medicinska istraživanja. 2025;58(1)83-87. doi: 10.5937/medi58-54885.
Francis A, Thomas J, Fallowfield L, Wallis M, Bartlett JM, Brookes C, et al. Addressing overtreatment of screen detected DCIS; the LORIS trial. Eur J Cancer. 2015;51(16):2296-303. doi: 10.1016/j.ejca.2015.07.017.
Schmitz RSJM, Engelhardt EG, Gerritsma MA, Sondermeijer CMT, Verschuur E, Houtzager J, et al. Active surveillance versus treatment in low-risk DCIS: Women's preferences in the LORD-trial. Eur J Cancer. 2023;192:113276. doi: 10.1016/j.ejca.2023.113276.
Hwang ES, Hyslop T, Lynch T, Frank E, Pinto D, Basila D, et al. The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS). BMJ Open. 2019;9(3):e026797. doi: 10.1136/bmjopen-2018-026797.
Chavez de Paz Villanueva C, Bonev V, Senthil M, Solomon N, Reeves ME, Garberoglio CA, et al. Factors associated with underestimation of invasive cancer in patients with ductal carcinoma in situ: precautions for active surveillance. JAMA Surg. 2017;152(11):1007-14. doi: 10.1001/jamasurg.2017.2181.
Silverstein MJ, Lagios MD. Treatment selection for patients with ductal carcinoma in situ (DCIS) of the breast using the University of Southern California/Van Nuys (USC/VNPI) prognostic index. Breast J. 2015;21(2):127-32. doi: 10.1111/tbj.12368.
Martins Maia C, Siderides C, Jaffer S, Weltz C, Cate S, Ahn S, et al. Mastectomy or margin re-excision? A nomogram for close/positive margins after lumpectomy for DCIS. Ann Surg Oncol. 2022;29(6):3740-48. doi: 10.1245/s10434-021-11293-3.
Solin LJ, Gray R, Baehner FL, Butler SM, Hughes LL, Yoshizawa C, et al. 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. doi: 10.1093/jnci/djt067.
Bremer T, Whitworth PW, Patel R, Savala J, Barry T, Lyle S, et al. 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. doi: 10.1158/1078-0432.CCR-18-0842.
Sagara Y, Mallory MA, Wong S, Aydogan F, DeSantis S, Barry WT, et al. Survival benefit of breast surgery for low-grade ductal carcinoma in situ: a population-based cohort study. JAMA Surg. 2015;150(8):739-45. doi: 10.1001/jamasurg.2015.0876.
Pan K, Nelson RA, Chlebowski RT, Piela R, Mullooly M, Simon MS, et al. Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women's Health Initiative. Breast Cancer Res Treat. 2024;207(1):65-79. doi: 10.1007/s10549-024-07327-5.
Nelson RA, Lai LL, Mortimer JE, Soto Perez De Celis E, Chlebowski RT, Kruper L. Prior DCIS and overall mortality in women with stage I breast cancer. Journal of Clinical Oncology. 2021;39(15_suppl):e12593–3. doi: 10.1200/JCO.2021.39.15_suppl.e12593.
Whitworth PW, Shah C, Vicini F, Rabinovitch R, Margenthaler JA, Warnberg F, et al. Identification of patients with DCIS with low-risk clinicopathology who benefit from radiation therapy with and without endocrine therapy after breast-conserving surgery assessed with the 7-gene biosignature. Journal of Clinical Oncology. 2024;42(16_suppl):528–8. doi: 10.1200/JCO.2024.42.16_suppl.528.
Houghton J, George WD, Cuzick J, Duggan C, Fentiman IS, Spittle M, et al. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet. 2003;362(9378):95-102. doi: 10.1016/s0140-6736(03)13859-7.
EORTC Breast Cancer Cooperative Group, EORTC Radiotherapy Group, Bijker N, Meijnen P, Peterse JL, Bogaerts J, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853--a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol. 2006;24(21):3381-7. doi: 10.1200/JCO.2006.06.1366.
Wärnberg F, Garmo H, Emdin S, Hedberg V, Adwall L, Sandelin K, et al. Effect of radiotherapy after breast-conserving surgery for ductal carcinoma in situ: 20 years follow-up in the randomized SweDCIS trial. J Clin Oncol. 2014;32(32):3613-8. doi: 10.1200/JCO.2014.56.2595.
Cuzick J, Sestak I, Pinder SE, Ellis IO, Forsyth S, Bundred NJ, et al. Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial. Lancet Oncol. 2011;12(1):21-9. doi: 10.1016/S1470-2045(10)70266-7.
Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103(6):478-88. doi: 10.1093/jnci/djr027.
McCormick B, Winter KA, Woodward W, Kuerer HM, Sneige N, Rakovitch E, et al. Randomized phase III trial evaluating radiation following surgical excision for good-risk ductal carcinoma in situ: long-term report from NRG oncology/RTOG 9804. J Clin Oncol. 2021;39(32):3574-82. doi: 10.1200/JCO.21.01083.
MacDonald HR, Silverstein MJ, Mabry H, Lee LA, Ye W, Holmes DR, et al. Local control in ductal carcinoma in situ treated by excision alone: incremental benefit of larger margins. Am J Surg. 2005;190(4):521–5.
Dunne C, Burke JP, Morrow M, Kell MR. Effect of margin status on local recurrence after breast conservation and radiation therapy for ductal carcinoma in situ. J Clin Oncol. 2009;27(10):1615-20. doi: 10.1200/JCO.2008.17.5182.
Morrow M, Van Zee KJ, Solin LJ, Houssami N, Chavez-MacGregor M, Harris JR, et al. Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. Pract Radiat Oncol. 2016;6(5):287-95. doi: 10.1016/j.prro.2016.06.011.
Vicini FA, Cecchini RS, White JR, Arthur DW, Julian TB, Rabinovitch RA, et al. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial. Lancet. 2019;394(10215):2155-64. doi: 10.1016/S0140-6736(19)32514-0.
Whelan TJ, Julian JA, Berrang TS, Kim DH, Germain I, Nichol AM, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019;394(10215):2165-72. doi: 10.1016/S0140-6736(19)32515-2.
Meattini I, Marrazzo L, Saieva C, Desideri I, Scotti V, Simontacchi G, et al. Accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-Florence trial. J Clin Oncol. 2020;38(35):4175-83. doi: 10.1200/JCO.20.00650.
Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, et al. 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet. 2016;387(10015):229-38. doi: 10.1016/S0140-6736(15)00471-7.
Moran MS, Zhao Y, Ma S, Kirova Y, Fourquet A, Chen P, et al. Association of radiotherapy boost for ductal carcinoma in situ with local control after whole-breast radiotherapy. JAMA Oncol. 2017;3(8):1060-68. doi: 10.1001/jamaoncol.2016.6948.
Margolese RG, Cecchini RS, Julian TB, Ganz PA, Costantino JP, Vallow LA, et al. Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet. 2016;387(10021):849-56. doi: 10.1016/S0140-6736(15)01168-X.
Forbes JF, Sestak I, Howell A, Bonanni B, Bundred N, Levy C, et al. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. Lancet. 2016;387(10021):866-73. doi: 10.1016/S0140-6736(15)01129-0.
