Value of a gene signature assay in patients with early breast cancer and intermediate risk: a single institution retrospective study

Abstract

Purpose In daily clinical practice, the indication for adjuvant chemotherapy (CT) is relatively easy to make in patients with early hormone-receptor-positive (HR+) breast cancer with either very poor or very good clinicopathological prognostic variables. However, this decision is much more difficult in patients with intermediate clinicopathological prognostic variables. Here, we evaluate the value of a gene-expression profile identified by the Prosigna gene signature assay in guiding treatment decision-making in patients with these intermediate features.

Methods A consecutive cohort of 577 HR + breast cancer patients surgically treated in a single institution between January 2012 and December 2012 was evaluated. From this population, pre- and post-menopausal patients with intermediate prognosis clinicopathological variables were identified and indication of adjuvant CT in these patients was recorded. The gene signature assay was performed retrospectively in this intermediate risk group. Descriptive statistics are presented.

Results Among 96 intermediate-risk patients, 64 postmenopausal patients underwent gene signature testing. Subtype distribution was as follows: Luminal A (N = 33; 51.6%), Luminal B (N = 31; 48.4%). Risk of recurrence (ROR) distribution was as follows: ROR-low (n = 16; 25%); ROR-intermediate (N = 26; 40.6%); and ROR-high (N = 22; 34.4%). CT was subsequently administered in 18.7%, 53.8% and 59.0% of the ROR-low, ROR-intermediate and ROR-high groups, respectively. With the use of the gene signature assay, 59.4% of the intermediate cases were re-classified to either ROR-low or ROR-high risk categories. In the ROR-intermediate group, 11/26 patients (42.3%) had Luminal A and 15/26 (57.7%) had Luminal B. Due to follow-up time constraints, no patient outcome results were evaluated.

Conclusion The gene signature assay provides clinically useful information and improved treatment decision-making in patients with intermediate risk based on clinicopathological factors. Determining the patient’s intrinsic subtype and ROR can aid clinicians in deciding whether CT should be indicated.

Key words:

• Adjuvant
• Breast cancer
• Genomic
• Intrinsic subtypes
• PAM50

Transparency

Acknowledgments

The authors thank Nanostring Technologies Inc. for financial support of this study.

Declaration of funding

This study was funded in part by Nanostring Technologies Inc., Seattle, WA, USA, and by funds from the following: Instituto de Salud Carlos III – PI13/01718, Banco Bilbao Vizcaya Argentaria (BBVA) Foundation and the Susan Komen Career Catalyst Grant.

Declaration of financial/other relationships

J.B and A.P. have disclosed that they are consultants to NanoString Technologies Inc. P.M. had disclosed that she is an employee of NanoString Technologies Inc. P.G. and S.G. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

The CMRO peer reviewer on this manuscript has no relevant financial or other relationships to disclose.

Notes

*Oncotype DX is a registered trademark of Genomic Health, Inc., Redwood City, CA, USA.

**Breast Cancer Index is a service mark of bioTheranostics, Inc., San Diego, CA, USA.

***EndoPredict is a registered trademark of Sividon Diagnostics GmbH, Cologne, Germany.