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01.12.2014 | Clinical trial | Ausgabe 3/2014

Breast Cancer Research and Treatment 3/2014

Gene expression profiling to predict the risk of locoregional recurrence in breast cancer: a pooled analysis

Breast Cancer Research and Treatment > Ausgabe 3/2014
C. A. Drukker, S. G. Elias, M. V. Nijenhuis, J. Wesseling, H. Bartelink, P. Elkhuizen, B. Fowble, P. W. Whitworth, R. R. Patel, F. A. de Snoo, L. J. van ’t Veer, P. D. Beitsch, E. J. Th. Rutgers
Wichtige Hinweise
C.A. Drukker, S.G. Elias, and M.V. Nijenhuis have contributed equally to this study.
The data in this study have been presented in a poster presentation at the San Antonio Breast Cancer Symposium in December 2012, in an oral presentation at the Annual meeting of the Dutch Society of Surgery of 2012, and the ECCO meeting of 2013.
An erratum to this article can be found at http://​dx.​doi.​org/​10.​1007/​s10549-015-3264-z.


The 70-gene signature (MammaPrint™) has been developed to predict the risk of distant metastases in breast cancer and select those patients who may benefit from adjuvant treatment. Given the strong association between locoregional and distant recurrence, we hypothesize that the 70-gene signature will also be able to predict the risk of locoregional recurrence (LRR). 1,053 breast cancer patients primarily treated with breast-conserving treatment or mastectomy at the Netherlands Cancer Institute between 1984 and 2006 were included. Adjuvant treatment consisted of radiotherapy, chemotherapy, and/or endocrine therapy as indicated by guidelines used at the time. All patients were included in various 70-gene signature validation studies. After a median follow-up of 8.96 years with 87 LRRs, patients with a high-risk 70-gene signature (n = 492) had an LRR risk of 12.6 % (95 % CI 9.7–15.8) at 10 years, compared to 6.1 % (95 % CI 4.1–8.5) for low-risk patients (n = 561; P < 0.001). Adjusting the 70-gene signature in a competing risk model for the clinicopathological factors such as age, tumour size, grade, hormone receptor status, LVI, axillary lymph node involvement, surgical treatment, endocrine treatment, and chemotherapy resulted in a multivariable HR of 1.73 (95 % CI 1.02–2.93; P = 0.042). Adding the signature to the model based on clinicopathological factors improved the discrimination, albeit non-significantly [C-index through 10 years changed from 0.731 (95 % CI 0.682–0.782) to 0.741 (95 % CI 0.693–0.790)]. Calibration of the prognostic models was excellent. The 70-gene signature is an independent prognostic factor for LRR. A significantly lower local recurrence risk was seen in patients with a low-risk 70-gene signature compared to those with high-risk 70-gene signature.

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