Strong Impact of MammaPrint and BluePrint on Treatment Decisions in Luminal Early Breast Cancer: Results of the WSG-PRIMe Study

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 2019 Feb 24

PMID 30796651

Citations 22

Authors

R Wuerstlein

R Kates

O Gluz

E M Grischke

C Schem

M Thill

S Hasmueller

A Kohler

B Otremba

F Griesinger

C Schindlbeck

A Trojan

F Otto

M Knauer

R Pusch

N Harbeck

Affiliations

Soon will be listed here.

Abstract

Purpose: The WSG-PRIMe Study prospectively evaluated the impact of the 70-gene signature MammaPrint® (MP) and the 80-gene molecular subtyping assay BluePrint® on clinical therapy decisions in luminal early breast cancer.

Methods: 452 hormone receptor (HR)-positive and HER2-negative patients were recruited (N0, N1). Physicians provided initial therapy recommendations based on clinicopathological factors. After prospective risk classification by MammaPrint/BluePrint was revealed, post-test treatment recommendations and actual treatment were recorded. Decisional Conflict and anxiety were measured by questionnaires.

Results: Post-test switch (in chemotherapy (CT) recommendation) occurred in 29.1% of cases. Overall, physician adherence to MP risk assessment was 92.3% for low-risk and 94.3% for high-risk MP scores. Adherence was remarkably high in "discordant" groups: 74.7% of physicians initially recommending CT switched to CT omission following low-risk MP scores; conversely, 88.9% of physicians initially recommending CT omission switched to CT recommendations following high-risk MP scores. Most patients (99.2%) recommended to forgo CT post-test and 21.3% of patients with post-test CT recommendations did not undergo CT; among MP low-risk patients with pre-test and post-test CT recommendations, 40% did not actually undergo CT. Luminal subtype assessment by BluePrint was discordant with IHC assessment in 34% of patients. Patients' State Anxiety scores improved significantly overall, particularly in MP low-risk patients. Trait Anxiety scores increased slightly in MP high risk and decreased slightly in MP low-risk patients.

Conclusions: MammaPrint and BluePrint test results strongly impacted physicians' therapy decisions in luminal EBC with up to three involved lymph nodes. The high adherence to genetically determined risk assessment represents a key prerequisite for achieving a personalized cost-effective approach to disease management of early breast cancer.

Citing Articles

Elevated expression of APOO as a potential prognostic marker in breast cancer: insights from bioinformatic analysis and experimental validation.

Bai Y, Tang Q, Zheng L, He J, Wang W, Li L BMC Med Genomics. 2024; 17(1):271.

PMID: 39558346 PMC: 11572147. DOI: 10.1186/s12920-024-02047-7.

How to Tackle Discordance in Adjuvant Chemotherapy Recommendations by Using Oncotype DX Results, in Early-Stage Breast Cancer.

Boer K, Kaposi A, Kocsis J, Horvath Z, Madaras B, Savolt A Cancers (Basel). 2024; 16(17).

PMID: 39272786 PMC: 11393992. DOI: 10.3390/cancers16172928.

Biomarkers in breast cancer 2024: an updated consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

Colomer R, Gonzalez-Farre B, Ballesteros A, Peg V, Bermejo B, Perez-Mies B Clin Transl Oncol. 2024; 26(12):2935-2951.

PMID: 38869741 PMC: 11564209. DOI: 10.1007/s12094-024-03541-1.

Real-world use of multigene signatures in early breast cancer: differences to clinical trials.

Licata L, De Sanctis R, Vingiani A, Cosentini D, Iorfida M, Rota Caremoli E Breast Cancer Res Treat. 2024; 205(1):39-48.

PMID: 38265569 PMC: 11062950. DOI: 10.1007/s10549-023-07227-0.

Oncotype DX results increase concordance in adjuvant chemotherapy recommendations for early-stage breast cancer.

Licata L, Viale G, Giuliano M, Curigliano G, Chavez-MacGregor M, Foldi J NPJ Breast Cancer. 2023; 9(1):51.

PMID: 37291235 PMC: 10250312. DOI: 10.1038/s41523-023-00559-6.

References

J van t Veer L, Dai H, van de Vijver M, He Y, Hart A, Mao M . Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002; 415(6871):530-6. DOI: 10.1038/415530a. View

van de Vijver M, He Y, Vant Veer L, Dai H, Hart A, Voskuil D . A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002; 347(25):1999-2009. DOI: 10.1056/NEJMoa021967. View

Buyse M, Loi S, Veer L, Viale G, Delorenzi M, Glas A . Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006; 98(17):1183-92. DOI: 10.1093/jnci/djj329. View

Vant Veer L, Bernards R . Enabling personalized cancer medicine through analysis of gene-expression patterns. Nature. 2008; 452(7187):564-70. DOI: 10.1038/nature06915. View

Wittner B, Sgroi D, Ryan P, Bruinsma T, Glas A, Male A . Analysis of the MammaPrint breast cancer assay in a predominantly postmenopausal cohort. Clin Cancer Res. 2008; 14(10):2988-93. PMC: 3089800. DOI: 10.1158/1078-0432.CCR-07-4723. View

Mook S, Schmidt M, Viale G, Pruneri G, Eekhout I, Floore A . The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. Breast Cancer Res Treat. 2008; 116(2):295-302. DOI: 10.1007/s10549-008-0130-2. View

Bueno-de-Mesquita J, Linn S, Keijzer R, Wesseling J, Nuyten D, van Krimpen C . Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat. 2008; 117(3):483-95. DOI: 10.1007/s10549-008-0191-2. View

Mook S, Schmidt M, Weigelt B, Kreike B, Eekhout I, van de Vijver M . The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age. Ann Oncol. 2009; 21(4):717-722. DOI: 10.1093/annonc/mdp388. View

Ishitobi M, Goranova T, Komoike Y, Motomura K, Koyama H, Glas A . Clinical utility of the 70-gene MammaPrint profile in a Japanese population. Jpn J Clin Oncol. 2010; 40(6):508-12. DOI: 10.1093/jjco/hyp195. View

10.

Krijgsman O, Roepman P, Zwart W, Carroll J, Tian S, de Snoo F . A diagnostic gene profile for molecular subtyping of breast cancer associated with treatment response. Breast Cancer Res Treat. 2011; 133(1):37-47. DOI: 10.1007/s10549-011-1683-z. View

11.

Drukker C, Bueno-de-Mesquita J, Retel V, van Harten W, van Tinteren H, Wesseling J . A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study. Int J Cancer. 2013; 133(4):929-36. PMC: 3734625. DOI: 10.1002/ijc.28082. View

12.

Gluck S, de Snoo F, Peeters J, Stork-Sloots L, Somlo G . Molecular subtyping of early-stage breast cancer identifies a group of patients who do not benefit from neoadjuvant chemotherapy. Breast Cancer Res Treat. 2013; 139(3):759-67. DOI: 10.1007/s10549-013-2572-4. View

13.

Goldhirsch A, Winer E, Coates A, Gelber R, Piccart-Gebhart M, Thurlimann B . Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013; 24(9):2206-23. PMC: 3755334. DOI: 10.1093/annonc/mdt303. View

14.

Cusumano P, Generali D, Ciruelos E, Manso L, Ghanem I, Lifrange E . European inter-institutional impact study of MammaPrint. Breast. 2014; 23(4):423-8. DOI: 10.1016/j.breast.2014.02.011. View

15.

Exner R, Bago-Horvath Z, Bartsch R, Mittlboeck M, Retel V, Fitzal F . The multigene signature MammaPrint impacts on multidisciplinary team decisions in ER+, HER2- early breast cancer. Br J Cancer. 2014; 111(5):837-42. PMC: 4150264. DOI: 10.1038/bjc.2014.339. View

16.

Whitworth P, Stork-Sloots L, de Snoo F, Richards P, Rotkis M, Beatty J . Chemosensitivity predicted by BluePrint 80-gene functional subtype and MammaPrint in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST). Ann Surg Oncol. 2014; 21(10):3261-7. PMC: 4161926. DOI: 10.1245/s10434-014-3908-y. View

17.

Bayraktar S, Royce M, Stork-Sloots L, de Snoo F, Gluck S . Molecular subtyping predicts pathologic tumor response in early-stage breast cancer treated with neoadjuvant docetaxel plus capecitabine with or without trastuzumab chemotherapy. Med Oncol. 2014; 31(10):163. DOI: 10.1007/s12032-014-0163-9. View

18.

Gupta A, Mutebi M, Bardia A . Gene-Expression-Based Predictors for Breast Cancer. Ann Surg Oncol. 2015; 22(11):3418-32. DOI: 10.1245/s10434-015-4703-0. View

19.

Yao K, Goldschmidt R, Turk M, Wesseling J, Stork-Sloots L, de Snoo F . Molecular subtyping improves diagnostic stratification of patients with primary breast cancer into prognostically defined risk groups. Breast Cancer Res Treat. 2015; 154(1):81-8. PMC: 4621695. DOI: 10.1007/s10549-015-3587-9. View

20.

Pohl H, Kotze M, Grant K, van der Merwe L, Pienaar F, Apffelstaedt J . Impact of MammaPrint on Clinical Decision-Making in South African Patients with Early-Stage Breast Cancer. Breast J. 2016; 22(4):442-6. DOI: 10.1111/tbj.12605. View