Abstract P4-06-13: Prospective analysis of molecular subtypes in triple negative breast cancer
Authors: Vetter Martina , Hartung Carolin , Lantzsch Tilmann , Hanf Volker , Uleer Christoph , Peschel Susanne , John Jutta , Buchmann Joerg , Weigert Edith , Buerrig Karl-Friedrich , Kantelhardt Eva-Johanna , Thomssen Christoph 
Published: March 2020

Introduction: Triple negative breast cancer (TNBC) is, in general, associated with unfavorable prognosis. However, TNBC it is a heterogenous disease. Thus, we analyzed the prognosis (RFI, OS) of TNBC in association to the molecular subtypes (according to Lehmann et al. 2011) and the prognostic markers uPA (urokinase-type plasminogen activator) and its inhibitor (uPA/PAI-1) within a prospective cohort of breast cancer patients.

Material & Methods: The PiA-study was designed as a multicenter cohort of early BC patients (n=1270, 2009 – 2011), treated according to national guidelines from six centers in Germany (Prognostic assessment in routine Application, NCT 01592825). All 153 patients with TNBC (12%) received chemotherapy (neoadjuvant, n=99, or adjuvant, n=54). Tumor characteristics were based on local pathology. IN 81 TNBC patients, fresh frozen tissue was obtained for central uPA/PAI-1 testing by ELISA (FEMTELLE BioMedica Diagnostic) was available. RNA of formalin fixed and paraffin embedded (FFPE) TNBC tumor material (n=125) was analyzed using the GeneChip® U133 Plus 2.0 (Affymetrix). The online Vanderbilt predictor tool was used to determine molecular subtypes (http://cbc.mc.vanderbilt.edu/tnbc).

Results: In the total cohort, 89.5% (CI 87.7-91.3) were free of RFI events after 5 years, the TNBC patients showed the poorest outcome with 72.8% (CI 65.5-80.1). In TNBC patients with a low uPA/PAI-1 status significantly more were free of RFI events than in patients with high uPA/PAI-1 status: 93% (CI 79.4-106.4) and 70.5% (CI 58.7-82.3), respectively. By the type 6-Vanderbilt tool, molecular subtypes were assigned as follows: BL1 18%, BL2 12%, IM 22%, M 12% MSL 6%, LAR: 14%, and UNS 16%. Using the type 4 tool we found for BL1 30%, BL2 18%, M 15%, LAR 18%, and UNS 19%. In all survival analysis, the patients with LAR subtype (n=23) had the lowest survival probability, with BL2 subtype N=22) the best: for 5 year RFI 58.7% (CI 29.4-71.8) versus 81.6% (CI 65.3-97.9). In those 54 TNBC patients who were treated with neoadjuvant chemotherapy, 46% of the patients had a pathologically confirmed complete response (ypT0/is ypN0).

Counclusion: TNBC is a heterogeneous disease. Patients with TNBC and low uPA/PAI-1 expression have a very low rate of disease recurrence. Particular attention has to be drawn to patients with the LAR subtype, since it seems to have the worst prognosis and may require androgen receptor directed treatment.

Outcome results of different endpointsn=125BL1 (n=38)BL2 (n=22)M (n=18)LAR (n=23)UNS (n=24)OS (95% CI)80.3% (67.2-93.4)95.2% (86.2-104.2)71.8% (50.8-92.8)65.2% (44.4-84.4)78.4% (61.5-95.3)RFS (95% CI)78.1% (64.6-91.6)81.6% (65.3-97.9)66.7% (44.9-88.5)50.6% (29.4-71.8)78.6% (62-95.2)RFI (95% CI)78.1% (64.6-91.6)81.6% (65.3-97.9)66.7% (44.9-88.5)58.7% (37.3-80.1)91.3% (79.7-102.9)BCSS (95% CI)80.3% (67.2-93.4)95.2% (86.2-104.2)71.8% (50.8-92.8)82.4% (66.7-98.1)90.9% (78.9-102.9)

Citation Format: Martina Vetter, Carolin Hartung, Tilmann Lantzsch, Volker Hanf, Christoph Uleer, Susanne Peschel, Jutta John, Joerg Buchmann, Edith Weigert, Karl-Friedrich Buerrig, Eva-Johanna Kantelhardt, Christoph Thomssen. Prospective analysis of molecular subtypes in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-06-13.