Abstract PS6-06: The 70-gene signature (MammaPrint) accurately predicts distant breast cancer recurrence risk in patients aged ≥70 years from the population-based observational FOCUS cohort
Authors: Noordhoek Iris , Bastiaannet Esther , Lujinovic Ersan , Esserman Laura , Wesseling Jelle , Scholten Astrid , Schröder Carolien P , Elias Sjoerd , de Glas Nienke A , Kroep Judith R , Portielje Johanneke EA , Kleijn Miranda , Liefers Gerrit-Jan J 
Published: February 2021

Abstract
Background Predicting breast cancer recurrence in patients aged ≥70 years is challenging, as they generally have more indolent tumors and a higher chance of dying of competing causes than younger patients. The 70-gene signature test (MammaPrint) has been shown to accurately predict recurrence in women with early breast cancer and up to 3 positive lymph nodes. Aim To study outcome related to MammaPrint result in patients aged ≥70 years with breast cancer using a population-based cohort. Methods The population-based FOCUS cohort included all 2095 consecutive patients with any stage breast cancer, diagnosed between 1997 and 2004, aged ≥65 years, in the Comprehensive Cancer Center region West, the Netherlands. In the present exploratory sub-study, patients from FOCUS with the following criteria were included: ≥70 years old, T1-2N0-3M0, hormone receptor positive, HER2 negative, no neo-adjuvant treatment and available tumor specimens. MammaPrint is a genomic risk profile based on microarray gene expression analysis, classifying patients as ultralow risk (M-ULR), low (not UL) risk (M-LR) or high risk (M-HR) of developing a recurrence. Patients were considered clinically low risk (C-LR) with T1-2N0 grade 1-2 tumors and clinically high risk (C-HR) with N+ or T2/grade 3 tumors. Primary endpoint was 10-year distant recurrence free interval (DRFi) in relation to genomic risk, estimated from cumulative incidence and Fine and Gray analyses to take competing mortality into account. Results In this study, 422 patients were included. Median age was 78 years, 238 patients (56%) had node negative disease, 235 patients (56%) had T2 tumors and 227 patients (54%) were C-LR. Most patients were treated with endocrine therapy (ET), and 22 patients (5%) were treated with chemotherapy (CT; table 1). Overall, 50 (12%) patients were M-ULR, 226 (53%) were M-LR and 146 (35%) were M-HR. Discrepancies were found between C and M risk groups in 18/50 M-ULR patients with C-HR, and 56/146 M-HR patients with C-LR. Of the 59 patients that experienced a recurrence during 10 years of follow-up, 44 (75%) were distant recurrences. In the M-ULR group, DRFi was 2% (95%CI 0-6) after 10 years of follow-up, this was 8% (95%CI 5-12) in the M-LR group and 17% (95%CI 11-23) in the M-HR group (p&lt;0.001). In the C-HR subgroup, none of the 18 M-ULR patients developed a recurrence, and DRFi was 10% (95%CI 3-16) in M-LR patients and 20% (95%CI 12-28) in M-HR patients (p=0.015). C risk alone was not able to predict distant recurrence risk (C-LR 8%, C-HR 14%, sHR 1.8 [95%CI 0.9-3.2); p=0.060; table 2). Conclusion MammaPrint accurately predicts 10-year DRFi in older patients with breast cancer. Patients classified as ultralow risk by MammaPrint had a very low chance of developing metastatic disease. Even in clinically high-risk patients who were M-ULR, recurrent disease did not occur 10 years after diagnosis. These findings are in line with published results of the STO-3 trial (JAMA Oncol, 2017) and provide foundation for de-escalation of treatment in older patients guided by genomic testing.
Table 1: Baseline characteristics. BCS = breast conserving surgery. RT = radiotherapyM-ULRM-LRM-HRTotal patientsN (%)50 (11.8)226 (53.6)146 (34.6)AgeMedian (IQR)79 (74-85)79 (74-84)77 (74-84)Histological grade [N (%)]I11 (22.0)39 (17.3)5 (3.4)II21 (42.0)92 (40.7)42 (28.8)III1 (2.0)31 (13.7)54 (37.0)Missing17 (34.0)64 (28.3)45 (30.8)T-stage [N (%)]Tis0 (0.0)2 (0.9)0 (0.0)T117 (34.0)111 (49.1)54 (37.0)T233 (66.0)113 (50.0)89 (61.0)Missing0 (0.0)0 (0.0)3 (2.0)N-stage [N (%)]N032 (64.0)140 (61.9)66 (45.2)N117 (34.0)72 (31.9)67 (45.9)N20 (0.0)6 (2.7)6 (4.1)N30 (0.0)2 (0.9)3 (2.1)Missing1 (2.0)6 (2.7)4 (2.7)Clinical risk [N (%)]Low32 (64.0)139 (61.5)56 (38.4)High18 (36.0)87 (38.5)90 (61.6)Local treatment [N (%)]None4 (8.0)5 (2.2)6 (4.1)BCS only3 (6.0)16 (7.1)13 (8.9)BCS + RT9 (18.0)62 (27.4)29 (19.9)Mastectomy34 (68.0)143 (63.3)98 (67.1)Adjuvant ET [N (%)]None24 (48.0)103 (45.6)40 (27.4)Tamoxifen17 (34.0)87 (38.5)80 (54.8)Aromatase inhibitor3 (6.0)11 (4.9)9 (6.2)Unspecified ET6 (12.0)25 (11.1)17 (11.6)Adjuvant CT [N (%)]No46 (92.0)217 (96.0)137 (93.8)Yes4 (8.0)9 (4.0)9 (6.2)
Table 2: Primary endpoint stratified by genomic and clinical risk. sHR=subdistribution hazard ratio.M-ULRM-LRM-HRTotalC-LRN=32 (14%). DRFi=3% (95%CI 0-9). sHR=1 (reference).N=139 (61%). DRFi=7% (95%CI 3-12). sHR=2.1 (95%CI 0.3-16.5).N=56 (25%). DRFi=13% (95%CI 4-21). sHR=4.3 (95%CI 0.5-34.7).N=227. DRFi=8% (95%CI 4-12).C-HRN=18 (9%).DRFi=0% (95%CI 0-0). sHR=N/A (n events=0).N=87 (45%). DRFi=10% (95%CI 3-16). sHR=1 (reference).N=90 (46%). DRFi=20% (95%CI 12-28). sHR=3.0 (95%CI 1.3-6.9).N=195. DRFi=14% (95%CI 9-19).TotalN=50 (12%). DRFi=2% (95%CI 0-6). sHR=1 (reference).N=226 (53%). DRFi=8% (95%CI 5-12). sHR=3.8 (95%CI 0.5-28.2).N=146 (35%). DRFi=17% (95%CI 11-23). sHR=9.8 (95%CI 1.3-72.6).N=422.
Citation Format: Iris Noordhoek, Esther Bastiaannet, Ersan Lujinovic, Laura Esserman, Jelle Wesseling, Astrid Scholten, Carolien P Schröder, Sjoerd Elias, Nienke A de Glas, Judith R Kroep, Johanneke EA Portielje, Miranda Kleijn, Gerrit-Jan J Liefers. The 70-gene signature (MammaPrint) accurately predicts distant breast cancer recurrence risk in patients aged ≥70 years from the population-based observational FOCUS cohort [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-06.