Abstract P3-07-27: Distinct biomarker features in triple-negative breast cancer metastases to the brain, liver and bone
Authors: Xiu J , Gatalica Z , Reddy S , Waisman J , Link J 
Published: May 2016

Background: Triple-negative breast cancer (TNBC) is characterized by its aggressive nature and accounts for a disproportionate number of metastatic disease cases and breast cancer-related deaths. Despite recent improvements, TNBC patients who develop metastatic diseases have limited treatment options. We investigated biomarkers from brain, liver and bone metastases collected from TNBC patients to identify therapeutic options and to examine molecular differences between the metastatic sites.

Method: Triple-negative breast cancer tumors referred to Caris Life Sciences (Phoenix, AZ) between 2009 and 2015 were tested with a combination of immunohistochemistry, fluorescent/chromogenic in-situ hybridization and sequencing (Next-generation and Sanger).

Result: 1570 TNBC tumors were analyzed, including 1297 tumors taken from breast, 54 from brain, 172 from liver and 47 from bone. Select biomarker frequencies of protein overexpression (IHC), gene amplification (ISH) and mutations (SEQ) are summarized in Table 1. Brain metastases showed the highest protein expression of TOPO2A and PDL1; liver metastases showed the highest expression of AR and SPARC, as well as the highest mutation rate of PIK3CA. Bone metastases showed the lowest expression of TS, RRM1 and ERCC1. BRCA1 and BRCA2 mutation rates ranged from 0-11% in various specimen sites.

Table 1Biomarker and MethodBreast Metastases (%)Brain Metastases (%)Liver Metastases (%)Bone Metastases (%)p value[pound]TOP2A IHC76100[sect]7339&lt;0.0001PDL1 IHC1540[sect]8170.03AR IHC151036[sect]260.0005SPARC IHC173040[sect]150.0027PIK3CA SEQ165.329[sect]250.036TS IHC[dagger]49542415[sect]&lt;0.0001RRM1 IHC[dagger]39433216[sect]0.006ERCC1 IHC[dagger]35554816[sect]0.002BRCA1 SEQ708n/ansBRCA2 SEQ11114n/ans[sect]:the group with the highest frequency of actionable results; [pound]:p values are calculated from comparing the group with the highest frequency with the lowest frequency using two tailed Fisher-Exact test, further detailed statistical analysis will be presented;[dagger]:low levels predict response to associated drugs; Ns: non-significant, i.e., p &gt;0.05; n/a: data not available due to low N

Conclusion: Distinct biomarker features identified in different metastatic sites in TNBC present the rationale to investigate differential treatment strategies. Based on biomarker results, etoposide, immune-modulatory agents may seem promising for brain metastases; anti-androgen therapies and nab-paclitaxel may be promising in treating liver metastases; while fluoropyrimidines, gemcitabine and platinum may be considered for TNBC patients with bone metastases.

Citation Format: Xiu J, Gatalica Z, Reddy S, Waisman J, Link J. Distinct biomarker features in triple-negative breast cancer metastases to the brain, liver and bone. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-27.