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

An Erratum to this article was published on 21 January 2015


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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No financial support was received to perform this study. We acknowledge the enormous efforts of M. van de Vijver, M. Buyse, P. Bedard, J. Bueno-de-Mesquita, S. Mook, M. Kok, M. Saghatchian, and colleagues to perform the various 70-gene signature studies included in this study. We thank N. Russell for her input on the interpretation of the preliminary data. We especially thank the data-managers at the Netherlands Cancer Institute for all their efforts in collection of the follow-up data.

Conflict of interest

LvtV is named inventor on the patent for the 70-gene signature used in this study. LvtV reports being shareholder in and part-time employed by Agendia Inc, the commercial company that markets the 70-gene signature as MammaPrint™. LvtV was supported by the Dutch Genomics Initiative ‘Cancer Genomics Centre’. FdS is director medical affairs of Agendia Inc. HB is a non-remunerated, non-stake holding member of the supervisory board of Agendia Inc. All other authors declare that they have no conflict of interest.

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Correspondence to E. J. Th. Rutgers.

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C.A. Drukker, S.G. Elias, and M.V. Nijenhuis have contributed equally to this study.

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Drukker, C.A., Elias, S.G., Nijenhuis, M.V. et al. Gene expression profiling to predict the risk of locoregional recurrence in breast cancer: a pooled analysis. Breast Cancer Res Treat 148, 599–613 (2014).

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  • Breast cancer
  • Risk prediction
  • Locoregional recurrence
  • 70-gene signature
  • Surgery
  • Radiation oncology