Subscribe to RSS
DOI: 10.1055/s-0031-1280291
© Georg Thieme Verlag KG Stuttgart · New York
Einfluss der prognostischen Faktoren auf die Therapie des duktalen Carcinoma in situ der Brust
Impact of Prognostic Markers on the Therapy of Ductal Breast Carcinoma in situPublication History
eingereicht 25.7.2011
revidiert 19.9.2011
akzeptiert 23.9.2011
Publication Date:
23 November 2011 (online)
![](https://www.thieme-connect.de/media/gebfra/201111/lookinside/thumbnails/10.1055-s-0031-1280291-1.jpg)
Zusammenfassung
Fragestellung: Nach heutigem Kenntnisstand wird das duktale Carcinoma in situ (DCIS) wie ein obligater Präkursor oder eine Vorstufe des invasiven Mammakarzinoms behandelt. Unabhängig von der Tumorbiologie gelten für alle Patientinnen die gleichen Therapieempfehlungen. Verlässliche prognostische Faktoren sollen uns in der Zukunft helfen, das individuelle Risiko besser einschätzen zu können und somit die Therapie maßgeschneidert zu gestalten (tailored therapy). Material und Methodik: Selektive Literaturrecherche. Ergebnisse: Offensichtlich werden heutzutage zahlreiche Patientinnen durch die übliche operative Therapie mit anschließender Bestrahlung übertherapiert. Leider fehlen uns bisher verlässliche prognostische Parameter, mit deren Hilfe Patientinnen mit niedrigem Risiko eindeutig identifiziert werden könnten. Einige klinische sowie histologische Prognosefaktoren werden zwar anerkannt, führen aber nach den aktuellen Leitlinien nicht zur Individualisierung der Therapie. Eine ganze Reihe von Biomarkern wurde mit der Fragestellung untersucht, ob durch den Nachweis im Tumorgewebe das Risikoprofil der jeweiligen Patientin besser definiert werden könnte. Bei manchen Markern wurde tatsächlich belegt, dass ihre Überexpression mit einem erhöhten Rezidivrisiko einhergeht. Leider wurden diese Experimente oft an einer sehr geringen Patientenzahl durchgeführt. Auch die Behandlungsmodalitäten weisen in einzelnen Studien Unterschiede auf. Dies erschwert die Auswertung der Ergebnisse. Prospektive Studien fehlen ganz. Schlussfolgerung: Die Therapie des DCIS wird sich zukünftig neben der Berücksichtigung der klassischen Kriterien auch an neuen Biomarkern orientieren müssen. Diese sind an großen Patientenkollektiven möglichst prospektiv auf ihre prognostische Bedeutung zu untersuchen.
Abstract
Purpose: According to current knowledge we treat ductal carcinoma in situ (DCIS) as an obligate precursor of invasive breast cancer. The same guidelines are applied to each patient irrespective of the characteristics of the neoplasm. In future, reliable prognostic factors should help us to assess individual risk better and tailor the therapy accordingly. Material und Methods: A review was done of the relevant literature. Results: We have been trying to individualize the therapy of DCIS for many years. Obviously we do overtreat some patients by performing surgery with adjuvant radiotherapy. Our knowledge of reliable prognostic factors for identifying low-risk patients is still inadequate. But while some clinical and histological criteria are accepted, they still do not have any influence on therapy according to the current guidelines. Dozens of biological markers were evaluated in order to find out whether their expression determines individual risk. As a matter of fact, there are markers indicating an increased risk of recurrence if detected in cancer tissue. Unfortunately the studies often included only a very small number of patients and the treatment approaches varied. This makes evaluation of the results quite difficult. No prospective studies were identified at all. Conclusion: In future, we should evaluate a combination of traditional criteria and novel biological markers prospectively in a large number of patients.
Schlüsselwörter
duktales Carcinoma in situ - Prognosefaktor - Biomarker
Key words
ductal carcinoma in situ - prognostic factor - biomarker
Literatur
- 1 Malek D, Rabe P. Mammographie-Screening-Programm. Im Internet: http://mammo-programm.de/cms_upload/datenpool/evaluationsbericht05-07_web.pdf Stand: 27.6.2011
- 41 Pfandzelter R, Wulfing U, Boedeker B et al. Diagnostic image quality of mammograms in German outpatient medical care. Geburtsh Frauenheilk. 2010; 70 998-1005
- 2 Allred D C, Mohsin S K, Fuqua S A. Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer. 2001; 8 47-61
- 42 Hauth E A, Wostmann A, Heindel W. Diagnostic imaging of invasive lobular breast carcinoma. Geburtsh Frauenheilk. 2009; 69 836-841
- 3 Sanders M E, Schuyler P A, Dupont W D et al. 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 2481-2484
- 4 Fong J, Kurniawan E D, Rose A K et al. Outcomes of screening-detected ductal carcinoma in situ treated with wide excision alone. Ann Surg Oncol. 2011; Jun 1 [Epub ahead of print]
- 43 Dieterich M, Dieterich H, Nestle-Kramling C et al. Certification of breast surgeons in Germany – AWO-gyn curriculum in an international comparison. Geburtsh Frauenheilk. 2009; 69 987-991
- 5 Dunne C, Burke J P, Morrow M et al. Effect of margin status on local recurrence after breast conservation and radiation therapy for ductal carcinoma in situ. J Clin Oncol. 2009; 27 1615-1620
- 6 Nitz U, Maass N. Empfehlungen gynäkologische Onkologie Kommission Mamma, deutsche Version 11.1.0, Stand März. Im Internet: http://www.ago-online.de/_download/unprotected/g_mamma_11_1_0_d_08_dcis.pdf Stand: 27.6.2011
- 7 Fisher B, Land S, Mamounas E et al. Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the national surgical adjuvant breast and bowel project experience. Semin Oncol. 2001; 28 400-418
- 8 Bijker N, Meijnen P, Peterse J L 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 3381-3387
- 9 Houghton J, George W D, Cuzick J UK Coordinating Committee on Cancer Research; Ductal Carcinoma in situ Working Party; DCIS trialists in the UK, Australia, and New Zealand 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 95-102
- 10 Emdin S O, Granstrand B, Ringberg A Swedish Breast Cancer Group et al. SweDCIS: Radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening. Acta Oncol. 2006; 45 536-543
- 11 Petrelli F, Barni S. Tamoxifen added to radiotherapy and surgery for the treatment of ductal carcinoma in situ of the breast: A meta-analysis of 2 randomized trials. Radiother Oncol. 2011; 100 195-199
- 12 Waddell B E, Stomper P C, DeFazio J L et al. Postexcision mammography is indicated after resection of ductal carcinoma-in-situ of the breast. Ann Surg Oncol. 2000; 7 665-668
- 44 Kaufmann M, Rody A. Breast cancer: reduced mortality by early detection and adjuvant therapy. Geburtsh Frauenheilk. 2009; 69 218-232
- 13 Silverstein M J, Lagios M D, Craig P H et al. A prognostic index for ductal carcinoma in situ of the breast. Cancer. 1996; 77 2267-2274
- 14 Silverstein M J. The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg. 2003; 186 337-343
- 15 Gilleard O, Goodman A, Cooper M et al. The significance of the Van Nuys prognostic index in the management of ductal carcinoma in situ. World J Surg Oncol. 2008; 6 61
- 16 Kelley L, Silverstein M, Guerra L. Analyzing the risk of recurrence after mastectomy for DCIS: a new use for the USC/Van Nuys Prognostic Index. Ann Surg Oncol. 2011; 18 459-462 Epub 2010 Sep 22
- 17 Kreienberg R, Kopp I, Albert U. Interdisziplinäre S3-Leitlinie für die Diagnostik, Therapie und Nachsorge des Mammakarzinoms. Im Internet: http://www.dggg.de/fileadmin/public_docs/Leitlinien/s3_ll_mammaca_11_02_2008.pdf Stand: 2.7.2011
- 18 Madu C O, Lu Y. Novel diagnostic biomarkers for prostate cancer. J Cancer. 2010; 1 150-177
- 45 Dietel M. Pathology in the year 2020. Geburtsh Frauenheilk. 2009; 69 212-217
- 19 Lari S A, Kuerer H M. Biological markers in DCIS and risk of breast recurrence: a systematic review. J Cancer. 2011; 2 232-261
- 20 Ringberg A, Anagnostaki L, Anderson H South Sweden Breast Cancer Group et al. Cell biological factors in ductal carcinoma in situ (DCIS) of the breast-relationship to ipsilateral local recurrence and histopathological characteristics. Eur J Cancer. 2001; 37 1514-1522
- 21 Provenzano E, Hopper J L, Giles G G et al. Biological markers that predict clinical recurrence in ductal carcinoma in situ of the breast. Eur J Cancer. 2003; 39 622-630
- 22 Roka S, Rudas M, Taucher S et al. High nuclear grade and negative estrogen receptor are significant risk factors for recurrence in DCIS. Eur J Surg Oncol. 2004; 30 243-247
- 23 Kerlikowske K, Molinaro A M, Gauthier M L et al. Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst. 2010; 102 627-637
- 24 Zhou W, Jirström K, Johansson C et al. Long-term survival of women with basal-like ductal carcinoma in situ of the breast: a population-based cohort study. BMC Cancer. 2010; 10 653
- 25 Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000; 182 311-322
- 26 Gauthier M L, Berman H K, Miller C et al. Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors. Cancer Cell. 2007; 12 479-491
- 27 Barnes N, Haywood P, Flint P et al. Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence. Br J Cancer. 2006; 94 253-258
- 28 Barnes N L, Khavari S, Boland G P et al. Absence of HER4 expression predicts recurrence of ductal carcinoma in situ of the breast. Clin Cancer Res. 2005; 11 2163-2168
- 29 Chasle J, Delozier T, Denoux Y et al. Immunohistochemical study of cell cycle regulatory proteins in intraductal breast carcinomas – a preliminary study. Eur J Cancer. 2003; 39 1363-1369
- 30 Jirström K, Ringberg A, Fernö M et al. Tissue microarray analyses of G1/S-regulatory proteins in ductal carcinoma in situ of the breast indicate that low cyclin D1 is associated with local recurrence. Br J Cancer. 2003; 89 1920-1926
- 31 Liggett Jr. W H, Sidransky D. Role of the p 16 tumor suppressor gene in cancer. J Clin Oncol. 1998; 16 1197-1206
- 32 Dotto G P. p 21(WAF1/Cip1): more than a break to the cell cycle?. Biochim Biophys Acta. 2000; 1471 M43-M56
- 33 Whibley C, Pharoah P D, Hollstein M. p 53 polymorphisms: cancer implications. Nat Rev Cancer. 2009; 9 95-107
- 34 Hieken T J, Farolan M, D'Alessandro S et al. Predicting the biologic behavior of ductal carcinoma in situ: an analysis of molecular markers. Surgery. 2001; 130 593-600
- 35 de Roos M A, de Bock G H, de Vries J et al. p 53 overexpression is a predictor of local recurrence after treatment for both in situ and invasive ductal carcinoma of the breast. J Surg Res. 2007; 140 109-114
- 36 Cornfield D B, Palazzo J P, Schwartz G F et al. The prognostic significance of multiple morphologic features and biologic markers in ductal carcinoma in situ of the breast: a study of a large cohort of patients treated with surgery alone. Cancer. 2004; 100 2317-2327
- 46 Fasching P A, Fehm T, Janni W et al. Breast cancer therapy – a state of the art review. Geburtsh Frauenheilk. 2010; 70 875-886
- 47 Ruschoff J, Nagelmeier I, Middel P et al. The role of Her-2/neu in the carcinogenesis of breast cancer – when and where?. Geburtsh Frauenheilk. 2009; 69 711-716
- 38 Witkiewicz A K, Freydin B, Chervoneva I et al. Stromal CD10 and SPARC expression in ductal carcinoma in situ (DCIS) patients predicts disease recurrence. Cancer Biol Ther. 2010; 10 391-396
- 39 Toussaint J, Durbecq V, Altintas S et al. Low CD10 mRNA expression identifies high-risk ductal carcinoma in situ (DCIS). PLoS One. 2010; 5 pii: e12100
- 40 Kulkarni S, Patil D B, Diaz L K et al. COX-2 and PPARgamma expression are potential markers of recurrence risk in mammary duct carcinoma in-situ. BMC Cancer. 2008; 8 36
MU Dr. Jan Böhm
Gynäkologie Abteilung
Henneberg Kliniken
Schleusinger Straße 17
98646 Hildburghausen
Email: bazy001@atlas.cz