Using a gene expression signature when controversy exists regarding the indication for adjuvant systemic treatment reduces the proportion of patients receiving adjuvant chemotherapy: a nationwide study

Straver

Dekker

et al. 2017

JCO

Gene-expression profiles increasingly are used in addition to conventional prognostic factors to guide adjuvant chemotherapy (CT) decisions. The Dutch guideline suggests use of validated geneexpression profiles in patients with estrogen receptor (ER) -positive, early-stage breast cancer without overt lymph node metastases. We aimed to assess the impact of a 70-gene signature (70-GS) test on CT decisions in patients with ER-positive, early-stage breast cancer. Patients and MethodsIn a prospective, observational, multicenter study in patients younger than 70 years old who had undergone surgery for ER-positive, early-stage breast cancer, physicians were asked whether they intended to administer adjuvant CT before deployment of the 70-GS test and after the test result was available. ResultsBetween October 1, 2013, and December 31, 2015, 660 patients, treated in 33 hospitals, were enrolled. Fifty-one percent of patients had pT1cN0, BRII, HER2-Neu-negative breast cancer. On the basis of conventional clinicopathological characteristics, physicians recommended CT in 270 (41%) of the 660 patients and recommended withholding CT in 107 (16%) of the 660 patients. For the remaining 43% of patients, the physicians were unsure and unable to give advice before 70-GS testing. In patients for whom CT was initially recommended or not recommended, 56% and 59%, respectively, were assigned to a low-risk profile by the 70-GS (k, 0.02; 95% CI, -0.08 to 0.11). After disclosure of the 70-GS test result, the preliminary advice was changed in 51% of patients who received a recommendation before testing; the definitive CT recommendation of the physician was in line with the 70-GS result in 96% of patients. ConclusionIn this prospective, multicenter study in a selection of patients with ER-positive, early-stage breast cancer, 70-GS use changed the physician-intended recommendation to administer CT in half of the patients.

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Impact of 70-Gene Signature Use on Adjuvant Chemotherapy Decisions in Patients With Estrogen Receptor–Positive Early Breast Cancer: Results of a Prospective Cohort Study

Straver

Dekker

et al. 2017

JCO

“…Some report an increase in chemotherapy administration 18 while others described a significant decrease in the administration of chemotherapy in ER1 early stage breast cancer patients after gene-expression profile use. [25][26][27][28][29] These studies reported changes in chemotherapy decisions in 19% to 44% of the cases when a gene-expression profile had been used. The present study illustrates that much of the observed varying impact of gene-expression profiles is the mere result of the different chemotherapy recommendations as stated in time-dependent clinical guidelines.…”

Section: Cancer Epidemiologymentioning

confidence: 99%

Changes over time in the impact of gene‐expression profiles on the administration of adjuvant chemotherapy in estrogen receptor positive early stage breast cancer patients: A nationwide study

Drukker

Elias

et al. 2016

Intl Journal of Cancer

Self Cite

Ten years ago gene-expression profiles were introduced to aid adjuvant chemotherapy decision making in breast cancer. Since then subsequent national guidelines gradually expanded the indication area for adjuvant chemotherapy. In this nation-wide study the evolution of the proportion of patients with estrogen-receptor positive (ER1) tumors receiving adjuvant chemotherapy in relation to gene-expression profile use in patient groups that became newly eligible for chemotherapy according to national guideline changes over time is assessed. Data on all surgically treated early breast cancer patients diagnosed between 2004-2006 and 2012-2014 were obtained from the Netherlands Cancer Registry. ER1/Her22 patients with tumorcharacteristics making them eligible for gene-expression testing in both cohorts and a discordant chemotherapy recommendation over time (2004 guideline not recommending and 2012 guideline recommending chemotherapy) were identified. We identified 3,864 patients eligible for gene-expression profile use during both periods. Gene-expression profiles were deployed in 5% and 35% of the patients in the respective periods. In both periods the majority of patients was assigned to a low genomic risk-profile (67% and 69%, respectively) and high adherence rates to the test result were observed (86% and 91%, respectively). Without deploying a gene-expression profile 8% and 52% (p <0.001) of the respective cohorts received chemotherapy while 21% and 28% of these patients received chemotherapy when a gene-expression profile was used (p 0.191). In conclusion, in ER1/Her22 early stage breast cancer patients gene-expression profile use was associated with a consistent proportion of patients receiving chemotherapy despite an adjusted guideline-based recommendation to administer chemotherapy.

“…We have recently reported that using GEPs leads to a decrease in CT administration in Dutch ER+ early-stage breast cancer patients. In this study we noticed that only a modest proportion of Dutch breast cancer patients for whom GEP is considered worthwhile actually receive a GEP [9]. …”

Section: Introductionmentioning

confidence: 99%

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

Schreuder²,

Elias³

et al. 2016

Public Health Genomics

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.