Abstract OT3-2-03: Prospective observational study of clinical outcomes for the NanoString® technologies Prosigna™ test by the West German Study Group
Authors: Wuerstlein Rachel , Sotlar Karl , Otremba Burkhard , Gluz Oleg , Pelz Enrico , Hofmann Daniel , Kates Ronald E , Witzel Isabelle , Schindlbeck Christian , Janni Wolfgang , Schem Christian , Tesch Hans , Harbeck Nadia 
Published: May 2015

Abstract
Background: Current diagnostic tools for breast cancer (BC), including screening, diagnostic breast imaging and biopsy, do not provide information about subtype classification. However, the subtype classification is crucial for the assessment of the recurrence risk and for the choice of optimal adjuvant treatment. A vast amount of data from recent research, clinical trials, and peer reviewed publications support the value of intrinsic subtyping based on gene expression analyses to assess prognosis and treatment options for patients with early BC.
Trial design: The multicenter (n=8), prospective study examines whether the Prosigna™ test influences physician and patient adjuvant treatment selection over and above currently used prognostic factors. It also examines the impact of the test results on patients’ reported outcomes including their decisional conflict status, anxiety levels, and functional status.
Prosigna™ is a standardized test measuring the expression levels of 50 classifier genes in formalin-fixed, paraffin-embedded tissue samples and provides a subtype classification based on the fundamental biology of individual patient’s tumor (intrinsic subtyping), as well as a prognostic score (risk of recurrence (ROR) score) that predicts the probability of cancer recurrence over 10 years.
Eligibility criteria: Postmenopausal women with resected N0, estrogen-receptor-positive (ER) (by immunohistochemistry (IHC); &gt;1% of stained tumor cells is considered positive), HER2-negative (IHC and/or in-situ fluorescence hybridization by local laboratory), early-stage invasive BC (T1-T2, pN0 (i+/mol+), M0). Patients must be able to give consent and must be eligible for treatment with adjuvant chemotherapy (Ctx) (ECOG performance status ≤1).
Patients with non-invasive (e.g. Paget’s disease, DCIS), ER-negative or HER2-positive BC must not be included. Metastatic disease and contraindications for adjuvant Ctx (age, ECOG &gt;1, significant comorbidities) are exclusion criteria. Patients unable to complete patient reported outcome surveys will be excluded.
Specific aims: Primary endpoint is the proportion of patients whose choice of treatment is changed as a result of receiving the Prosigna™ result.
Secondary endpoints include the proportion of patients whose choice of treatment is changed stratified by ROR groups (low, intermediate, high) and who have cancer recurrence risk proximal to the cutoff points between risk strata (± 5% from cutoff point). Investigators’ confidence in treatment recommendations before/after Prosigna™ results and change in patients’ decisional conflict status, anxiety levels, and functional status, stratified by cancer recurrence risk strata, will be investigated. Rate and severity of treatment-related adverse events stratified by whether patient received adjuvant Ctx and agreement in molecular subtyping between Prosigna™ and local IHC will be evaluated.
Statistical methods: Sample size of 200 produces a one-sided 95% lower-limit CI with a distance from the sample proportion to the lower limit that is equal to 0.05 when the sample proportion is 0.25.
Present and target accrual: A total of 200 patients will be included, current accrual is n=111 as of 3rd June 2014.
Citation Format: Rachel Wuerstlein, Karl Sotlar, Burkhard Otremba, Oleg Gluz, Enrico Pelz, Daniel Hofmann, Ronald E Kates, Isabelle Witzel, Christian Schindlbeck, Wolfgang Janni, Christian Schem, Hans Tesch, Nadia Harbeck. Prospective observational study of clinical outcomes for the NanoString® technologies Prosigna™ test by the West German Study Group [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 OT3-2-03.