Abstract

Abstract Background Gene signatures (GS), such as the 70-gene signature (MammaPrint™), are used as an adjunct to clinicopathological factors to predict outcome in breast cancer patients. According to the current Dutch national guidelines GS can be used in case of ambivalence regarding the benefit of adjuvant chemotherapy (ACT). While the impact of GS on the individual patient is well established, less is known about the impact on predefined patient cohorts in terms of an increase or decrease of the proportion of patients who receive ACT. Methods Patients surgically treated for primary breast cancer between November 2011 and April 2013 were selected from the Netherlands Cancer Registry. The administration of ACT in these patients was evaluated in relation to the use of the 70-gene signature (In the Netherlands the 70-gene signature is the most frequently used gene expression profile). Based on the Dutch guidelines clinicians might be ambivalent regarding the administration of ACT in the following subgroups: patients < 70 yrs with pN0, BRI tumours >2cm (group A), patients <70 yrs. with pN0, BRII tumours >1cm (group B) and patients < 70 yrs classified as pN1micro, BR I or II (group C). Results A total of 13.122 patients were identified in the Cancer Registry. The 70 –gene signature was used in 794 patients; 19 in group A, 227 in group B, 62 in group C, and 456 (57.4%) did not fulfil the ambivalence criteria. In the latter patients, clinicopathological characteristics were contributed as follows: BR III tumours > 1cm (n=204), age > 70 (n=71), tumours<1cm (n=88), HER2+ (n=92), ER- (n=83) and N+ (n=166). In the predefined groups A, B and C, ACT was administered less when the 70-gene signature had been used (P= 0.019, 0.016 and 0.117 respectively; see Table 1). The administration of ACT was in line with the test result of the 70-gene signature in 89%, 86% and 84% of the patients in group A,B and C respectively. In categories other than the predefined A,B and C an inverse relation was seen: more ACT was given when a GS was used (38% without and 54% with a GS) and adherence to the gene expression test result was lower. Table 1: administration of adjuvant chemotherapy in relation to the use of MammaPrint NChemotherapy (%)p-valueGroup ANo Mammaprint12261 (47%) Mammaprint194 (21%)0.019 Low riks/High risk15/3 ACT in line with GS89% Broup BNo Mammaprint1229507 (41%) MammaPrint22675 (33%)0.016 Low/ risk/High risk125/74 ACT in line with GS86% Group CNo MammaPrint397209 (53%) MammaPrint6226 (42%)0.117 Low risk/High risk34/23 ACT in line with GS84% Conclusion The proportion of patients who receive ACT decreased when a GS was used in predefined cohorts of patients for whom ambivalence exists regarding the use of ACT. The majority of patients for whom a GS was used did not fit these predefined categories and in subsets an inverse relation was seen: the use of a gene signature was associated with a higher chance of receiving ACT. Citation Format: Anne Kuijer, Annelotte CM van Bommel, Margriet van der Heiden- van der Loo, Carolien A Drukker, Thijs van Dalen. The 70-gene signature affects adjuvant systemic treatment decisions in breast cancer patients: A population-based, observational study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-17.

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