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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS6-06-PS6-06
    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.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    In: Genes, Chromosomes and Cancer, Wiley, Vol. 61, No. 3 ( 2022-03), p. 148-160
    Abstract: MammaPrint® (MP) is a 70‐gene signature that stratifies early‐stage breast cancer patients into low‐ and high risk of distant relapse. Further stratification of MP risk results identifies four risk subgroups, ultra‐low (UL), low, high 1, and high 2, with specific prognostic and predictive outcomes. BluePrint® (BP) is an 80‐gene signature that classifies breast tumors as basal, luminal, or HER2 molecular subtype. To gain insight into their biological significance, we annotated the MP 70‐ and BP 80‐genes with respect to the 10 hallmarks of cancer (HoC). Furthermore, we related gene expression profiles of the extreme ends of the MP low‐ and high‐risk patients (here called, ultra‐low (UL) and ultra‐high (UH) or High2, respectively), to the 10 HoC per BP subtype by differential gene expression and pathway analysis. MP and BP gene functions reflected all 10 HoCs. Most MP and BP genes were associated with sustaining proliferative signaling, followed by genome instability and mutation categories. Based on the gene expression profiles, UL and UH subgroup pathways were down ‐or upregulated, respectively, reflecting proliferative and metastatic features, such as G2M checkpoint, DNA repair, oxidative phosphorylation, immune invasion, PI3K/AKT/mTOR signaling, and hypoxia pathways. Notably, the UH HER2‐type was enriched in several immune signaling pathways, such as IL2/STAT5 signaling and TNFα signaling via NFκB. Our results show that MP and BP gene signatures represent and capture all 10 HoCs and highlight underlying biological processes of MP extreme samples, which might guide treatment decisions as the signature captures the full spectrum of early breast cancers.
    Type of Medium: Online Resource
    ISSN: 1045-2257 , 1098-2264
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1018988-9
    detail.hit.zdb_id: 1492641-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2020
    In:  Clinical Cancer Research Vol. 26, No. 18_Supplement ( 2020-09-15), p. PO-056-PO-056
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 18_Supplement ( 2020-09-15), p. PO-056-PO-056
    Abstract: Introduction: With the recent worldwide outbreak of COVID-19, it became clear that certain comorbidities are associated with an increased risk of complications and death. Several publications have reported an increased rate of ICU admission and mortality in cancer patients. This has led to guidelines advising more conservative approaches to cancer therapy, including chemotherapy. In the absence of prospective, disease-specific outcome data, there is a risk of overestimating the risk of COVID-19 and thus increasing cancer-specific mortality or of underestimating. MammaPrint has been validated for selecting clinically high-risk breast cancer patients in whom chemotherapy can be avoided safely. Methods: We evaluated the current published literature related to the potential risk of breast cancer and chemotherapy in association with COVID-19. We estimated the potential risk of severe events in COVID-19 breast cancer patients receiving adjuvant chemotherapy to assess whether MammaPrint could help us further in making chemotherapy decisions specific to an infectious epidemic risk. Results: The risk of COVID-19 morbidity and mortality in patients receiving chemotherapy could be greater than 1.5 to 2 times higher than usual. However, other associated conditions frequently found in the breast cancer population seem to still play a significant role in a worse outcome. We found no data to quantify the effect of chemotherapy or data allowing us to adapt the MammaPrint Score to risk in an infectious epidemic. Conclusion: Adjuvant chemotherapy carries a potential risk for morbidity and mortality. Data from the current literature do not show the magnitude of the added risk for breast cancer patients on adjuvant chemotherapy in association with SARS Cov-2 infection. By using MammaPrint in hormone receptor-positive patients with up to three nodes in whom chemotherapy is considered, the treatment-related risk can be limited, allowing safe de-escalation of therapy without increased cancer-specific mortality. We plan to pursue the statistical question of how the level of risk at any of the sites on the spectrum relates to distant metastasis-free survival so that mortality risks can be better estimated during an infection. Citation Format: Elizabeth M. Murray, Ettienne J. Myburgh, Ersan Lujinovic, Lorenza Mittempergher, Duncan J. Robertson, Josephus J. de Jager, Maritha J. Kotze. Using MammaPrint to reduce the need for chemotherapy in early breast cancer during the COVID-19 pandemic [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-056.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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