Factors Associated with the Use of Gene Expression Profiles in Estrogen Receptor-Positive Early-Stage Breast Cancer Patients: A Nationwide Study

Abstract

Background: Breast cancer guidelines suggest the use of gene expression profiles (GEPs) in estrogen receptor-positive (ER+) breast cancer patients in whom controversy exists regarding adjuvant chemotherapy benefit based on traditional prognostic factors alone. We evaluated the current use of GEPs in these patients in the Netherlands. Patients and Methods: Primary breast cancer patients treated between January 1, 2011 and December 31, 2014 and eligible for GEP use according to the Dutch national breast cancer guideline were identified in the Netherlands Cancer Registry: ER+ patients <70 years with grade 1 tumors >2 cm or grade 2 tumors 1-2 cm without overt lymph node metastases (pN0-Nmi). Mixed-effect logistic regression analysis was performed to associate characteristics of patients, tumors and hospitals with GEP use. Results: GEPs were increasingly deployed: 12% of eligible patients received a GEP in 2011 versus 46% in 2014. Lobular versus ductal morphology (OR 0.58, 95% CI 0.47-0.72), pN1mi status (versus pN0, OR 0.52, 95% CI 0.40-0.68), and tumor size (>3 cm vs. >2 cm, OR 0.33, 95% CI 0.14-0.88) were inversely associated with GEP use. High socioeconomic status (SES) (OR 1.32, 95% CI 1.06-1.64) and younger age (OR 0.96/year increasing age, 95% CI 0.95-0.96) were positively associated with GEP use. GEP use per hospital did vary, but no predefined institutional factors remained independently associated with GEP use. Conclusion: GEP use increased over time and was influenced by patient- and tumor-associated factors as well as by SES.

Impact of gene-expression profiling in patients with early breast cancer when applied outside the guideline directed indication area

“…An unexpected observation in a previous population-based study was the frequent use of GEPs outside the guideline-intended indicated area, i.e. in patients in whom clinical guidelines state a clear recommendation to administer or withhold CT based on clinicopathological factors alone [12]. GEP use in this patient group raises the question whether the GEP test results influenced CT administration in these patients.…”

The Changing Role of Gene-Expression Profiling in the Era of De-escalating Adjuvant Chemotherapy in Early-Stage Breast Cancer

“…Patients with grade III tumors were not included, because these patients were not considered candidates for GEP use. Although the 70-GS and OncotypeDx are both commercially available in the Netherlands, OncotypeDx was rarely used during the study period 16. We therefore focused on the use and impact of 70-GS only.…”

Use and Impact of the 21-Gene Recurrence Score in Relation to the Clinical Risk of Developing Metastases in Early Breast Cancer Patients in the Netherlands

“…The test was deployed in a limited number of patients, comprising < 10% of the GEPs that were used during the study period [12]. Approximately half of the tests were used outside the intended indication area.…”

“…In a previous population-based study, we observed an increase in 70-GS use in Dutch breast cancer patients within the aforementioned guideline-directed indicated area in recent years [12]. When the 70-GS was used in accordance with the Dutch guideline, high adherence rates to the 70-GS test result were observed [13].…”