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01-02-2012 | Preclinical Study

Hematogenous and lymphatic tumor cell dissemination may be detected in patients diagnosed with ductal carcinoma in situ of the breast

Authors: Malgorzata Banys, Ines Gruber, Natalia Krawczyk, Sven Becker, Ralph Kurth, Diethelm Wallwiener, Jolanta Jakubowska, Jürgen Hoffmann, Ralf Rothmund, Annette Staebler, Tanja Fehm

Published in: Breast Cancer Research and Treatment | Issue 3/2012

Abstract

Tumor cell dissemination in bone marrow (BM) and lymph nodes is considered an important step in systemic disease progression and is associated with poor prognosis. Only invasive cancers are assumed to shed isolated tumor cells (ITC) into the bloodstream and infiltrate lymph nodes. However, latest studies indicate that tumor cell dissemination may occur before stroma invasion, i.e., in ductal carcinoma in situ (DCIS). Therefore, the purpose of this study was to examine the incidence of ITC in bone marrow and sentinel lymph nodes (SN) in patients diagnosed with DCIS and its correlation with clinicopathological factors. 266 patients who were treated at the Department of Gynecology and Obstetrics (University Hospital Tuebingen, Germany) between 2003 and 2009 with DCIS were included into this study. BM aspirates were analyzed by immunocytochemistry (pancytokeratin antibody A45-B/B3) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. SN were analyzed in 221 of these patients by extensive step sectioning and hematoxylin–eosin staining. In 34 of 266 patients (13%), ITC in BM could be detected. There was no correlation found between tumor size, grading, histology, or Van Nuys Prognostic Index and tumor cell dissemination. In two cases, metastatic spread into lymph nodes was observed (pN1mi), whereas in one case, ITC in lymph nodes were detected; however, additional sectioning and immunohistochemical staining of the primary lesion in the cases with positive SN did not reveal invasive cancer. Interestingly, all the three patients were BM negative. Tumor cell dissemination may be detected in patients diagnosed with DCIS. Either these cells have started already to disseminate from preinvasive mammary lesions or from occult invasive tumors or represent the earliest step of microinvasion in a preinvasive lesion. The clinical relevance of these cells has to be further evaluated.

Sakorafas GH, Farley DR, Peros G (2008) Recent advances and current controversies in the management of DCIS of the breast. Cancer Treat Rev 34(6):483–497PubMedCrossRef

Ernster VL, Ballard-Barbash R, Barlow WE, Zheng Y, Weaver DL, Cutter G, Yankaskas BC, Rosenberg R, Carney PA, Kerlikowske K, Taplin SH, Urban N, Geller BM (2002) Detection of ductal carcinoma in situ in women undergoing screening mammography. J Natl Cancer Inst 94(20):1546–1554PubMedCrossRef

Ernster VL, Barclay J, Kerlikowske K, Grady D, Henderson C (1996) Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA 275(12):913–918PubMedCrossRef

Ernster VL, Barclay J, Kerlikowske K, Wilkie H, Ballard-Barbash R (2000) Mortality among women with ductal carcinoma in situ of the breast in the population-based surveillance, epidemiology and end results program. Arch Intern Med 160(7):953–958PubMedCrossRef

Kelly TA, Kim JA, Patrick R, Grundfest S, Crowe JP (2003) Axillary lymph node metastases in patients with a final diagnosis of ductal carcinoma in situ. Am J Surg 186(4):368–370PubMedCrossRef

Intra M, Rotmensz N, Veronesi P, Colleoni M, Iodice S, Paganelli G, Viale G, Veronesi U (2008) Sentinel node biopsy is not a standard procedure in ductal carcinoma in situ of the breast: the experience of the European institute of oncology on 854 patients in 10 years. Ann Surg 247(2):315–319PubMedCrossRef

Husemann Y, Geigl JB, Schubert F, Musiani P, Meyer M, Burghart E, Forni G, Eils R, Fehm T, Riethmuller G, Klein CA (2008) Systemic spread is an early step in breast cancer. Cancer Cell 13(1):58–68PubMedCrossRef

Klein CA (2009) Parallel progression of primary tumours and metastases. Nat Rev Cancer 9(4):302–312PubMedCrossRef

Jamshidi K, Swaim WR (1971) Bone marrow biopsy with unaltered architecture: a new biopsy device. J Lab Clin Med 77(2):335–342PubMed

10.

Fehm T, Braun S, Muller V, Janni W, Gebauer G, Marth C, Schindlbeck C, Wallwiener D, Borgen E, Naume B, Pantel K, Solomayer E (2006) A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer 107(5):885–892PubMedCrossRef

11.

Bauer KD, de la Torre-Bueno J, Diel IJ, Hawes D, Decker WJ, Priddy C, Bossy B, Ludmann S, Yamamoto K, Masih AS, Espinoza FP, Harrington DS (2000) Reliable and sensitive analysis of occult bone marrow metastases using automated cellular imaging. Clin Cancer Res 6(9):3552–3559PubMed

12.

Borgen E, Naume B, Nesland JM, Kvalheim G, Beiske K, Fodstad O, Diel IJ, Solomayer EF, Theocharous P, Coombes RC, Smith BM, Wunder E, Marolleau J-P, Garci J, Pantel K (1999) Standardization of the immunocytochemical detection of cancer cells in BM and blood I establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy 1(5):377–388PubMedCrossRef

13.

McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2006) Reporting recommendations for tumor marker prognostic studies (REMARK). Breast Cancer Res Treat 100(2):229–235PubMedCrossRef

14.

Wellings SR, Jensen HM (1973) On the origin and progression of ductal carcinoma in the human breast. J Natl Cancer Inst 50(5):1111–1118PubMed

15.

Broders AC (1932) Carcinoma in situ contrasted with benign penetrating epithelium. JAMA 99:1670–1674CrossRef

16.

Bloodgood JC (1931) Border-line breast tumors. Ann Surg 93:235–249PubMedCrossRef

17.

Chin K, de Solorzano CO, Knowles D, Jones A, Chou W, Rodriguez EG, Kuo WL, Ljung BM, Chew K, Myambo K, Miranda M, Krig S, Garbe J, Stampfer M, Yaswen P, Gray JW, Lockett SJ (2004) In situ analyses of genome instability in breast cancer. Nat Genet 36(9):984–988PubMedCrossRef

18.

Cutuli B, Cohen-Solal-Le Nir C, De Lafontan B, Mignotte H, Fichet V, Fay R, Servent V, Giard S, Charra-Brunaud C, Auvray H, Penault-Llorca F, Charpentier JC (2001) Ductal carcinoma in situ of the breast results of conservative and radical treatments in 716 patients. Eur J Cancer 37(18):2365–2372PubMedCrossRef

19.

Lara JF, Young SM, Velilla RE, Santoro EJ, Templeton SF (2003) The relevance of occult axillary micrometastasis in ductal carcinoma in situ: a clinicopathologic study with long-term follow-up. Cancer 98(10):2105–2113PubMedCrossRef

20.

Weaver DL (2003) Occult “micrometastases” in ductal carcinoma in situ: investigative implications for sentinel lymph node biopsy. Cancer 98(10):2083–2087PubMedCrossRef

21.

van Deurzen CH, Hobbelink MG, van Hillegersberg R, van Diest PJ (2007) Is there an indication for sentinel node biopsy in patients with ductal carcinoma in situ of the breast? A review. Eur J Cancer 43(6):993–1001PubMedCrossRef

22.

Cox CE, Nguyen K, Gray RJ, Salud C, Ku NN, Dupont E, Hutson L, Peltz E, Whitehead G, Reintgen D, Cantor A (2001) Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS? Am Surg 67(6):513–519 discussion 519-521PubMed

23.

Yen TW, Hunt KK, Ross MI, Mirza NQ, Babiera GV, Meric-Bernstam F, Singletary SE, Symmans WF, Giordano SH, Feig BW, Ames FC, Kuerer HM (2005) Predictors of invasive breast cancer in patients with an initial diagnosis of ductal carcinoma in situ: a guide to selective use of sentinel lymph node biopsy in management of ductal carcinoma in situ. J Am Coll Surg 200(4):516–526PubMedCrossRef

24.

Feldman SM, Krag DN, McNally RK, Moor BB, Weaver DL, Klein P (1999) Limitation in gamma probe localization of the sentinel node in breast cancer patients with large excisional biopsy. J Am Coll Surg 188(3):248–254PubMedCrossRef

25.

Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd, Bodurka DC, Burstein HJ, Cochran AJ, Cody HS 3rd, Edge SB, Galper S, Hayman JA, Kim TY, Perkins CL, Podoloff DA, Sivasubramaniam VH, Turner RR, Wahl R, Weaver DL, Wolff AC, Winer EP (2005) American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23(30):7703–7720PubMedCrossRef

26.

Friberg S, Mattson S (1997) On the growth rates of human malignant tumors: implications for medical decision making. J Surg Oncol 65(4):284–297PubMedCrossRef

27.

Schmidt-Kittler O, Ragg T, Daskalakis A, Granzow M, Ahr A, Blankenstein TJ, Kaufmann M, Diebold J, Arnholdt H, Muller P, Bischoff J, Harich D, Schlimok G, Riethmuller G, Eils R, Klein CA (2003) From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc Natl Acad Sci USA 100(13):7737–7742PubMedCrossRef

28.

Engel J, Eckel R, Kerr J, Schmidt M, Furstenberger G, Richter R, Sauer H, Senn HJ, Holzel D (2003) The process of metastasisation for breast cancer. Eur J Cancer 39(12):1794–1806PubMedCrossRef

29.

Fehm T, Krawczyk N, Solomayer EF, Becker-Pergola G, Durr-Storzer S, Neubauer H, Seeger H, Staebler A, Wallwiener D, Becker S (2008) ER alpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients. Breast Cancer Res 10(5):R76PubMedCrossRef

30.

Krawczyk N, Banys M, Neubauer H, Solomayer EF, Gall C, Hahn M, Becker S, Bachmann R, Wallwiener D, Fehm T (2009) HER2 status on persistent disseminated tumor cells after adjuvant therapy may differ from initial HER2 status on primary tumor. Anticancer Res 29(10):4019–4024PubMed

31.

Podsypanina K, Du YC, Jechlinger M, Beverly LJ, Hambardzumyan D, Varmus H (2008) Seeding and propagation of untransformed mouse mammary cells in the lung. Science 321(5897):1841–1844PubMedCrossRef

32.

Intra M, Veronesi P, Mazzarol G, Galimberti V, Luini A, Sacchini V, Trifiro G, Gentilini O, Pruneri G, Naninato P, Torres F, Paganelli G, Viale G, Veronesi U (2003) Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast. Arch Surg 138(3):309–313PubMedCrossRef

33.

Mabry H, Giuliano AE, Silverstein MJ (2006) What is the value of axillary dissection or sentinel node biopsy in patients with ductal carcinoma in situ? Am J Surg 192(4):455–457PubMedCrossRef

34.

Katz A, Gage I, Evans S, Shaffer M, Fleury T, Smith FP, Flax R, Drogula C, Petrucci P, Magnant C (2006) Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer. Am J Surg 191(6):761–766PubMedCrossRef

35.

Zavagno G, Carcoforo P, Marconato R, Franchini Z, Scalco G, Burelli P, Pietrarota P, Lise M, Mencarelli R, Capitanio G, Ballarin A, Pierobon ME, Marconato G, Nitti D (2005) Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast. BMC Cancer 5:28PubMedCrossRef

36.

Pendas S, Dauway E, Giuliano R, Ku N, Cox CE, Reintgen DS (2000) Sentinel node biopsy in ductal carcinoma in situ patients. Ann Surg Oncol 7(1):15–20PubMedCrossRef

37.

Klauber-DeMore N, Tan LK, Liberman L, Kaptain S, Fey J, Borgen P, Heerdt A, Montgomery L, Paglia M, Petrek JA, Cody HS, Van Zee KJ (2000) Sentinel lymph node biopsy: is it indicated in patients with high-risk ductal carcinoma-in situ and ductal carcinoma-in situ with microinvasion? Ann Surg Oncol 7(9):636–642PubMedCrossRef

38.

Leidenius M, Salmenkivi K, von Smitten K, Heikkila P (2006) Tumour-positive sentinel node findings in patients with ductal carcinoma in situ. J Surg Oncol 94(5):380–384PubMedCrossRef

39.

Sakr R, Barranger E, Antoine M, Prugnolle H, Darai E, Uzan S (2006) Ductal carcinoma in situ: value of sentinel lymph node biopsy. J Surg Oncol 94(5):426–430PubMedCrossRef

40.

Di Saverio S, Catena F, Santini D, Ansaloni L, Fogacci T, Mignani S, Leone A, Gazzotti F, Gagliardi S, De Cataldis A, Taffurelli M (2008) 259 Patients with DCIS of the breast applying USC/Van Nuys Prognostic Index: a retrospective review with long term follow up. Breast Cancer Res Treat 109(3):405–416PubMedCrossRef

Title: Hematogenous and lymphatic tumor cell dissemination may be detected in patients diagnosed with ductal carcinoma in situ of the breast
Authors: Malgorzata Banys
Ines Gruber
Natalia Krawczyk
Sven Becker
Ralph Kurth
Diethelm Wallwiener
Jolanta Jakubowska
Jürgen Hoffmann
Ralf Rothmund
Annette Staebler
Tanja Fehm
Publication date: 01-02-2012
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-011-1478-2

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