The impact of age and nodal status on variations in oncotype DX testing and adjuvant treatment

Iles, Kathleen; Roberson, Mya L.; Spanheimer, Philip M.; Gallagher, Kristalyn; Ollila, David W.; Strassle, Paula D.; Downs-Canner, Stephanie

doi:10.1038/s41523-022-00394-1

Cited by 14 publications

(7 citation statements)

References 41 publications

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“…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). ER+/LN-/HER2-patients derive low or no benefit from chemotherapy if a tumour is classified as RS low (32) and in line with this, Barni et al found a 38% relative reduction of chemotherapy usage in 230 older patients on the basis of RS (39).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…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). ER+/LN-/HER2-patients derive low or no benefit from chemotherapy if a tumour is classified as RS low(32) and in line with this, Barni 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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“…Thus, we feel that policy and guidance restraints have been a barrier to more effective diagnostic testing and treatment individualization among older patients with BC, a finding supported in the literature. 41,42 Our QI exercise is framed within a PDSA cycle approach, 19 with a follow-up planned in 2 years to analyze the clinical pattern of RS utilization and related chemotherapy prescription. The effort will also include a reassessment of the time from surgery to initiation of chemotherapy on the basis of the new criteria to understand the impact of reflex testing patterns on treatment delays of >8 weeks, most likely to be detrimental on the outcomes.…”

Section: Discussionmentioning

confidence: 99%

Identifying Patterns and Barriers in OncotypeDX Recurrence Score Testing in Older Patients With Early-Stage, Estrogen Receptor–Positive Breast Cancer: Implications for Guidance and Reimbursement

Trapani

Jin

Block

et al. 2023

JCO Oncology Practice

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PURPOSE To evaluate the clinical patterns of utilization of OncotypeDX Recurrence Score (RS) in early-stage, hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer (BC) at an academic center with previously established internal reflex testing guidelines. METHODS RS testing in accordance with preexisting reflex criteria and predictors of utilization outside of reflex criteria were retrospectively analyzed for the years 2019-2021 in a quality improvement evaluation. Patients were grouped according to OncotypeDX testing within (cohort A) or outside (cohort B) of predefined criteria which included a cap at age older than 65 years. RESULTS Of 1,687 patients whose tumors had RS testing, 1,087 were in cohort A and 600 in cohort B. In cohort B, nearly half of patients were older than 65 years (n = 279; IQR, 67-72 years). For patients older than 65 years, those with RS testing were younger (median age: 69 v 73 years), with higher grade cancers (G2-3: 84.9% v 54.7%) and were more likely to be treated with chemotherapy (15.4% v 4.1%). Issues for implementation of RS testing in older patients were identified, including potential structural barriers related to the current policy on the reimbursements of genomic tests. CONCLUSION Internal guidelines may facilitate standardized utilization of the RS in early-BC. Our data suggest that clinicians preferred broader utilization of RS across the age spectrum, with therapeutically important consequences. Modifying the current policy for reimbursement of RS testing and in internal reflexive testing criteria for those older than 65 years is warranted.

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“…Recent studies demonstrated that RS correlates with recurrence rates and adjuvant treatment response [5,9,[12][13][14]. The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) both recommended the use of Oncotype Dx RS testing in patients with ER + /HER2 − breast cancers [15,16]. Moreover, the Guidelines Development Group of the European Commission Initiative on Breast Cancer recently prioritized a clinical question on the use of multigene test to guide the use of adjuvant chemotherapy in ER + , HER2 − , and lymph node-negative or up to 3 lymph node-positive invasive breast cancer [17].…”

Section: Introductionmentioning

confidence: 99%

MRI-Based Radiomics Approach Predicts Tumor Recurrence in ER + /HER2 − Early Breast Cancer Patients

et al. 2023

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Oncotype Dx Recurrence Score (RS) has been validated in patients with ER + /HER2 − invasive breast carcinoma to estimate patient risk of recurrence and guide the use of adjuvant chemotherapy. We investigated the role of MRI-based radiomics features extracted from the tumor and the peritumoral tissues to predict the risk of tumor recurrence. A total of 62 patients with biopsy-proved ER + /HER2 − breast cancer who underwent pre-treatment MRI and Oncotype Dx were included. An RS > 25 was considered discriminant between low-intermediate and high risk of tumor recurrence. Two readers segmented each tumor. Radiomics features were extracted from the tumor and the peritumoral tissues. Partial least square (PLS) regression was used as the multivariate machine learning algorithm. PLS β-weights of radiomics features included the 5% features with the largest β-weights in magnitude (top 5%). Leave-one-out nested cross-validation (nCV) was used to achieve hyperparameter optimization and evaluate the generalizable performance of the procedure. The diagnostic performance of the radiomics model was assessed through receiver operating characteristic (ROC) analysis. A null hypothesis probability threshold of 5% was chosen (p < 0.05). The exploratory analysis for the complete dataset revealed an average absolute correlation among features of 0.51. The nCV framework delivered an AUC of 0.76 (p = 1.1∙10−3). When combining “early” and “peak” DCE images of only T or TST, a tendency toward statistical significance was obtained for TST with an AUC of 0.61 (p = 0.05). The 47 features included in the top 5% were balanced between T and TST (23 and 24, respectively). Moreover, 33/47 (70%) were texture-related, and 25/47 (53%) were derived from high-resolution images (1 mm). A radiomics-based machine learning approach shows the potential to accurately predict the recurrence risk in early ER + /HER2 − breast cancer patients.

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The impact of age and nodal status on variations in oncotype DX testing and adjuvant treatment

Cited by 14 publications

References 41 publications

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

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

Identifying Patterns and Barriers in OncotypeDX Recurrence Score Testing in Older Patients With Early-Stage, Estrogen Receptor–Positive Breast Cancer: Implications for Guidance and Reimbursement

MRI-Based Radiomics Approach Predicts Tumor Recurrence in ER + /HER2 − Early Breast Cancer Patients

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