Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention studyReport as inadecuate

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BMC Cancer

, 12:616

Clinical oncology


BackgroundPresence of disseminated tumor cells DTCs in bone marrow BM after completion of systemic adjuvant treatment predicts reduced survival in breast cancer. The present study explores the use of DTCs to identify adjuvant insufficiently treated patients to be offered secondary adjuvant treatment intervention, and as a surrogate marker for therapy response.

MethodsA total of 1121 patients with pN1-3 or pT1c-T2G2-3pN0-status were enrolled. All had completed primary surgery and received 6 cycles of anthracycline-containing chemotherapy. BM-aspiration was performed 8-12 weeks after chemotherapy BM1, followed by a second BM-aspiration 6 months later BM2. DTC-status was determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. If DTCs were present at BM2, docetaxel 100 mg-m, 3qw, 6 courses was administered, followed by DTC-analysis 1 month BM3 and 13 months BM4 after the last docetaxel infusion.

ResultsClinical follow-up FU is still ongoing. Here, the descriptive data from the study are presented. Of 1085 patients with a reported DTC result at both BM1 and BM2, 94 patients 8.7% were BM1 positive and 83 7.6% were BM2 positive. The concordance between BM1 and BM2 was 86.5%. Both at BM1 and BM2 DTC-status was significantly associated with lobular carcinomas p = 0.02 and p = 0.03, respectively; chi-square. In addition, DTC-status at BM2 was also associated with pN-status p = 0.009 and pT-status p = 0.03. At BM1 28.8% and 12.8% of the DTC-positive patients had ≥2 DTCs and ≥3 DTCs, respectively. At BM2, the corresponding frequencies were 47.0% and 25.3%. Of 72 docetaxel-treated patients analyzed at BM3 and-or BM4, only 15 20.8% had persistent DTCs. Of 17 patients with ≥3 DTCs before docetaxel treatment, 12 patients turned negative after treatment 70.6%. The change to DTC-negativity was associated with the presence of ductal carcinoma p = 0.009.

ConclusionsAfter docetaxel treatment, the majority of patients experienced disappearance of DTCs. As this is not a randomized trial, the results can be due to effects of adjuvant docetaxel-endocrine-trastuzumab treatment and-or limitations of the methodology. The clinical significance of these results awaits mature FU data, but indicates a possibility for clinical use of DTC-status as a residual disease-monitoring tool and as a surrogate marker of treatment response.

Trial registrationClin Trials Gov NCT00248703

AbbreviationsDTCDisseminated tumor cell

BMBone marrow

pN1-3 and pT1c-T2G2-3pN0Standard tumor-node-metastasis TMN classification according to AJCC-UICC 2002

3qwEvery third week


pN-statusHistopathological lymph node status

pT-statusHistopathological primary tumor size status

EREstrogen receptors

PRProgesterone receptors

HER2-statusHuman epidermal growth factor receptor 2

IDCInfiltrating ductal carcinoma

ILCInfiltrating lobular carcinoma


FECFluorouracil epirubicine cyclophosphamide

MNCMononuclear cell

mAbMononuclear antibody

APAAPAlkaline phosphatase-monoclonal mouse anti-alkaline phosphatase

TNMTumor-node-metastasis staging system

pN1Metastasis to 1-3 axillary lymph nodes

HRHazard ratio

CIConfidence interval

DFSDisease free survival

OSOverall survival

FISHFluorescence in situ hybridization

CGHComparative genomic hybridization

multi-marker IFMulti-marker immunoflourecence

EMTEpithelial-mesenchymal transition

SBGScandinavian Breast Group.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-12-616 contains supplementary material, which is available to authorized users.

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Author: Marit Synnestvedt - Elin Borgen - Erik Wist - Gro Wiedswang - Kjetil Weyde - Terje Risberg - Christian Kersten - Ingvil Mj

Source: https://link.springer.com/


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