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Multicenter Study
. 2025 Jan;209(2):331-340.
doi: 10.1007/s10549-024-07496-3. Epub 2024 Sep 30.

70-Gene signature-guided adjuvant systemic treatment adjustments in early-stage ER+ breast cancer patients: 7-year follow-up of a prospective multicenter cohort study

Eline E F Verreck  1   2   3 , Anne Kuijer  4 , Julia E C van Steenhoven  5   6 , José H Volders  5 , Annette W G van der Velden  7 , Sabine Siesling  8   9 , Anja N H Timmer-Bonte  10 , Tineke J Smilde  11 , Alex L T Imholz  12 , Charlotte F J M Blanken-Peeters  13 , Bart de Valk  14 , Suzan Vrijaldenhoven  15 , Willem B Lastdrager  16 , Annebeth W Haringhuizen  17 , Jarmo C B Hunting  18 , Sjoerd Hovenga  19 , Peter Nieboer  20 , Hanneke M Zuetenhorst  21 , Geert W M Tetteroo  22 , Carolien H Smorenburg  23 , Marissa C van Maaren  8   9 , Thijs van Dalen  24   25
Affiliations
Multicenter Study

70-Gene signature-guided adjuvant systemic treatment adjustments in early-stage ER+ breast cancer patients: 7-year follow-up of a prospective multicenter cohort study

Eline E F Verreck et al. Breast Cancer Res Treat. 2025 Jan.

Abstract

Background: A previous prospective multicenter study revealed the change of the oncologists' chemotherapy advice due to the 70-Gene signature (GS) test result in half of the estrogen receptor-positive (ER+) invasive early-stage breast cancer patients with disputable chemotherapy indication. This resulted in less patients receiving chemotherapy. This study aims to complement these results by the 7-year oncological outcomes according to the 70-GS test result and the oncologists' pre-test advice.

Methods: Patients operated for early-stage ER+ breast cancer with disputable chemotherapy indication, had been prospectively included between 2013 and 2015. Oncologists were asked whether they intended to administer adjuvant chemotherapy before deployment of the 70-GS test. Information on adjuvant systemic treatment and oncological outcome was obtained through active follow-up by data managers of the Netherlands Cancer Registry. The primary endpoint of this study was distant metastasis-free survival (DMFS) according to the genomic risk. Exploratory analyses were done to evaluate DMFS in relation to the oncologists' pre-test advice.

Results: After a median follow-up of 7 years, distant metastases were diagnosed in 23 of the 606 patients (3.8%) and 36 (5.9%) patients had died. The DMFS rate for the 357 70-GS genomic low-risk patients was 94.2% (95% CI 91.2-96.2) and 89.1% for the 249 genomic high-risk patients (95% CI 84.3-92.4). Of the low-risk patients 3% had received chemotherapy compared to 80% of the high-risk patients. For the subgroups based on the pre-test oncologists' advice (no chemotherapy/chemotherapy/unsure) there were no clinically relevant differences in DMFS (89.8, 93.2 and 92.0%, respectively), while comparable proportions of patients had received chemotherapy.

Conclusions: In patients with early-stage ER+ breast cancer with a disputable chemotherapy indication it is sensible to deploy the 70-GS to better select patients for adjuvant chemotherapy.

Keywords: 70-Gene Signature; Chemotherapy decision; Luminal breast cancer.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Kaplan–Meier analysis of A distant metastasis-free survival (DMFS), B disease-free survival (DFS), C overall survival (OS) stratified by the 70-GS genomic risk
Fig. 2
Fig. 2
Kaplan–Meier analysis of distant metastasis-free survival (DMFS) in the 70-Gene Signature (70-GS) high-risk group in relation to the administered chemotherapy
Fig. 3
Fig. 3
Kaplan–Meier analysis of A distant metastasis-free survival (DMFS), B disease-free survival (DFS), C overall survival (OS) stratified by the oncologists’ pre-test chemotherapy advice
See this image and copyright information in PMC

References

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