Abstract 171P
Background
Adjuvant tamoxifen and aromatase inhibitors are currently widely used to treat oestrogen receptor positive (ER+) breast cancers (BC). Guidelines recommend the use of endocrine therapy for up to 10 years. However, not all patients need endocrine treatment. To avoid overtreatment, a test that identifies patients with excellent prognosis is mandatory. The 70-gene FDA-approved MammaPrint with 3 predefined thresholds has potential to select patients that have an excellent survival without chemotherapy and only limited or no tamoxifen treatment. Our goal was to validate the MammaPrint Ultralow Risk classification in patients treated with 0-3 years of tamoxifen.
Methods
In the Dutch IKA trial (1982-1994), postmenopausal patients with non-metastatic BC were randomized between no or limited adjuvant tamoxifen treatment (0 - 3 years) without receiving chemotherapy. Suitable FFPE tumor material of ER+HER2- patients with 0 – 3 positive lymph nodes was selected for MammaPrint testing at Agendia®, blinded to outcome data. The Hazard ratio (HR) for recurrence-free interval (RFI) was stratified for lymph node status.
Results
We classified 135 patients using the MammaPrint score with increasing risk for recurrence (see table). The median follow-up time was 13 years. The average years of tamoxifen treatment was not significantly different between the Ultralow and High risk patients. High risk MammaPrint patients had 22/53 (42%) RFI events. In contrast, Ultralow risk patients had 2/23 (9%) RFI events of which none were in the node negative patients. This year 20-year follow-up data and BC specific survival will be collected. Table: 171P
Results of patients tested with the MammaPrint using 3 predefined thresholds
| Ultralow risk | Low risk | High risk | |
| Number of patients | 23 | 59 | 53 |
| Patients not receiving tamoxifen | 5 [22%] | 13 [22%] | 16 [30%] |
| Average years of tamoxifen [Q1 – Q3] | 2.3 [1.0 - 3.2] | 2.0 [1.0 - 3.0] | 1.6 [1.0 - 2.9] |
| RFI events in node-negative patients | 0/16 [0%] | 2/33 [6%] | 10/31 [32%] |
| RFI events in node-positive patients | 2/7 [29%] | 5/26 [19%] | 12/22 [55%] |
| RFI (adjusted HR) | Ref | 1.10 [0.2- 5.3] | 4.86 [1.1 - 20.7] |
Conclusions
Postmenopausal N0 patients with an Ultralow MammaPrint score have excellent long-term RFI after surgery and limited or no endocrine treatment. This is in line with published results of the STO-3 randomized clinical trial and supports the concept that it is possible to reduce the duration of adjuvant tamoxifen treatment in selected ER+/HER2- patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Central ethics committee of the Netherlands Cancer Institute.
Funding
Agendia.
Disclosure
M. Kleijn: Full/Part-time employment: Agendia. A. Glas: Full/Part-time employment: Agendia. J.B. Vermorken: Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Innate Pharma; Advisory/Consultancy: Merck-Serono; Advisory/Consultancy: Merck Sharp & Dome Corp; Advisory/Consultancy: PCI Biotech; Advisory/Consultancy: Synthon Biopharmaceuticals; Advisory/Consultancy: Debiopharm; Advisory/Consultancy: Cue Biopharma; Advisory/Consultancy: WntResearch; Speaker Bureau/Expert testimony, lecture fee: Merck-Serono; Speaker Bureau/Expert testimony, lecture fee: MSD; Speaker Bureau/Expert testimony, lecture fee: BMS. S. Linn: Research grant/Funding (self): ZonMw; Research grant/Funding (self): A sisters hope; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Cergentis; Advisory/Consultancy, Non-remunerated activity/ies: IBM; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Non-remunerated activity/ies: Roche; Research grant/Funding (institution): Agendia; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Eurocept-pharmaceuticals; Research grant/Funding (institution), Non-remunerated activity/ies: Genentech; Research grant/Funding (institution), Non-remunerated activity/ies: Novartis; Research grant/Funding (institution), Non-remunerated activity/ies: Pfizer; Research grant/Funding (institution): Roche; Research grant/Funding (institution), Non-remunerated activity/ies: Tesaro; Research grant/Funding (institution), Non-remunerated activity/ies: Immunomedics; Research grant/Funding (institution): Bayer. All other authors have declared no conflicts of interest.