Validation of the 70-gene signature test (MammaPrint) to identify patients with breast cancer aged ≥ 70 years with ultralow risk of distant recurrence: A population-based cohort study

Noordhoek, Iris; Bastiaannet, E.; Glas, Nienke A. de; Scheepens, J.; Esserman, Laura J.; Wesseling, Jelle; Scholten, Astrid N.; Schröder, Carolien P.; Elias, Sjoerd G.; Kroep, Judith R.; Portielje, Johanneke E.A.; Kleijn, Miranda; Liefers, G.J.

doi:10.1016/j.jgo.2022.07.006

Cited by 8 publications

(5 citation statements)

References 21 publications

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“…Consistently, a retrospective population-based analysis of 418 elderly patients with HR+ breast cancer confirmed a similar percentage of ultralow-risk breast cancers (12.0%), with a 10-year distant recurrence rate of 2% in this patient subgroup, even among patients at high risk according to clinicopathological criteria and even in the absence of adjuvant treatments in about half of the cases ( 42 ). The excellent prognosis of ultralow-risk breast cancers was additionally reported in the prospective RASTER study.…”

Section: De-escalation: Omission Of Endocrine Treatmentmentioning

confidence: 54%

Gene Expression Assays to Tailor Adjuvant Endocrine Therapy for HR+/HER2− Breast Cancer

Bottosso,

Miglietta,

Vernaci

et al. 2024

Clinical Cancer Research

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Adjuvant endocrine therapy represents the standard of care for almost all HR+/HER2- breast cancers and different agents and durations are currently available. In this context, the tailoring and optimization of adjuvant endocrine treatment by reducing unnecessary toxic treatment while taking into account the biological heterogeneity of HR+/HER2- breast cancer represents a clinical priority. There is therefore a significant need for the integration of biological biomarkers in the choice of adjuvant endocrine therapy beyond currently used clinicopathological characteristics. Several gene-expression assays have been developed to identify patients with HR+/HER2- breast cancer who will not derive benefit from the addition of adjuvant chemotherapy. By enhancing risk stratification and predicting therapeutic response, genomic assays have also shown to be a promising tool for optimizing endocrine treatment decision. We here review evidence supporting the use of most common commercially available gene-expression assays (Oncotype DX, MammaPrint, Breast Cancer Index, Prosigna and EndoPredict) in tailoring adjuvant endocrine therapy. Available data on the use of genomic tests to inform extended adjuvant treatment choice based on the risk of late relapse and on the estimated benefit of a prolonged endocrine therapy are discussed. Moreover, preliminary evidence regarding the use of genomic assays to inform de-escalation of endocrine treatment, such as shorter durations or omission, for low risk patients are reviewed. Overall, gene expression assays are emerging as potential tools to further personalize adjuvant treatment for patients with HR+/HER2- breast cancers.

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Section: De-escalation: Omission Of Endocrine Treatmentmentioning

confidence: 54%

Gene Expression Assays to Tailor Adjuvant Endocrine Therapy for HR+/HER2− Breast Cancer

Bottosso,

Miglietta,

Vernaci

et al. 2024

Clinical Cancer Research

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“…Nonetheless, unresolved questions remain regarding the effect of withholding or decreasing ET on very long‐term outcome 43,45 . The gUL classification has also been examined in additional lower LOE analyses, producing broadly consistent results 46,47 …”

Section: Resultsmentioning

confidence: 96%

“…43,45 The gUL classification has also been examined in additional lower LOE analyses, producing broadly consistent results. 46,47 A prospective-retrospective analysis by Dubsky 48 and colleagues utilized the biomarker cohort of the ABCSG-8 study to evaluate Mammaprint. Of 1347 ER+ ET-treated patients, only 658 (49%) could be included due to RNA degradation in the formalinfixed, paraffin-embedded (FFPE) samples.…”

Section: Mammaprint ®mentioning

confidence: 99%

Selecting postoperative adjuvant systemic therapy for early‐stage breast cancer: An updated assessment and systematic review of leading commercially available gene expression assays

Hyams,

Bareket‐Samish,

Rocha

et al. 2024

Journal of Surgical Oncology

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Gene expression assays (GEAs) can guide treatment for early‐stage breast cancer. Several large prospective randomized clinical trials, and numerous additional studies, now provide new information for selecting an appropriate GEA. This systematic review builds upon prior reviews, with a focus on five widely commercialized GEAs (Breast Cancer Index®, EndoPredict®, MammaPrint®, Oncotype DX®, and Prosigna®). The comprehensive dataset available provides a contemporary opportunity to assess each GEA's utility as a prognosticator and/or predictor of adjuvant therapy benefit.

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“…A recent study of the 70-gene signature in 89 older patients showed no statistical difference from the MINDACT clinical trial implying that this signature could also be applied to older breast cancer patients (36). Furthermore, in a study with 418 older patients above 70, Noordhoek et al found that patients with high clinical risk based on the St. Gallen risk classification, but classified as ultra-low risk by the 70-gene signature, had excellent prognosis (37). Regarding RS, Iles et al showed a decline in its usage with increasing age and a higher prevalence of low-risk classifications in patients above 70 years old (38).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in a study with 418 older patients above 70, Noordhoek et al . found that patients with high clinical risk based on the St. Gallen risk classification, but classified as ultra-low risk by the 70-gene signature, had excellent prognosis(37). Regarding RS, Iles et al .…”

Section: Discussionmentioning

confidence: 99%

Clinically relevant gene signatures provide independent prognostic information in older breast cancer patients

Castresana-Aguirre

Johansson

Matikas

et al. 2023

Preprint

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Background: Older breast cancer patients (≥70 years) are under-represented in clinical trials and remain an undertreated population. Gene signatures have been shown to add prognostic information beyond that of routine clinico-pathological factors, however their utility in older breast cancer patients remains unclear. As such, the aim of this study was to determine if gene signatures can provide prognostic information that may aid treatment decisions for older breast cancer patients. Patients and methods: Research versions of the genomic grade index (GGI), 70-gene, 21-gene recurrence score (RS), cell cycle score (CCS), PAM50 Risk of Recurrence score - Proliferation (ROR-P), and PAM50 signatures were applied to 39 breast cancer datasets totalling 9583 patients. After filtering based on age ≥ 70 years, the presence of Estrogen Receptor (ER) and survival information availability 871 patients remained. The prognostic capacity of signatures was tested in all (n=871), ER-positive/lymph node-positive (ER+/LN+, n=335) and ER-positive/lymph node-negative (ER+/LN-, n=374) patients using Kaplan-Meier and multivariable Cox proportional hazard modeling. Models were adjusted for tumour size, grade, ER, lymph node status and hormonal therapy. Recurrence Free Survival (RFS) censored at 10 years was used as the clinical endpoint. Results: All gene signatures were statistically significant in Kaplan-Meier analysis of all and ER+/LN+ patients (Log-rank P < 0.001). This significance remained in multivariable analysis (Cox proportional hazards, P ≤ 0.05). In ER+/LN- patients the GGI, 70-gene, CCS, ROR-P, and PAM50 signatures were significant in Kaplan-Meier analysis (Log-rank P ≤ 0.05) but only the 70-gene, CCS, ROR-P, and PAM50 signatures remained so in multivariable analysis (Cox proportional hazards, P ≤ 0.05). Conclusions: In general, we found that gene signatures provide prognostic information in survival analyses of all, ER+/LN+ and ER+/LN- older (≥70 years) breast cancer patients, suggesting a potential role in aiding treatment decision in older patients.

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Validation of the 70-gene signature test (MammaPrint) to identify patients with breast cancer aged ≥ 70 years with ultralow risk of distant recurrence: A population-based cohort study

Cited by 8 publications

References 21 publications

Gene Expression Assays to Tailor Adjuvant Endocrine Therapy for HR+/HER2− Breast Cancer

Gene Expression Assays to Tailor Adjuvant Endocrine Therapy for HR+/HER2− Breast Cancer

Selecting postoperative adjuvant systemic therapy for early‐stage breast cancer: An updated assessment and systematic review of leading commercially available gene expression assays

Clinically relevant gene signatures provide independent prognostic information in older breast cancer patients

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