Abstract P6-05-09: Subtyping of triple negative breast cancer by a novel immunohistochemistry panel: Assessing the correlation between subtypes and clinical outcomes
Authors: Walsh EM , Shalaby A , Murillo LS , Webber MJ , Kerin MJ , Glynn SA , Callagy GM , Ingoldsby H , Keane MM 
Published: May 2016

Background:

Triple negative breast cancer (TNBC) is characterised by a lack of expression of oestrogen receptor and progesterone receptor and lack of HER2 overexpression. Using gene expression profiling, TNBC can be subtyped into six subtypes: BL1,BL2,IM,M,MSL&LAR. However, gene profiling is not yet routine in clinical practice. Also, despite the heterogeneity of TNBC, standard of care remains combination chemotherapy without targeted therapy. It is necessary to identify TNBC subtypes with differing responses to chemotherapy. In chemoresistant TNBCs, identifying alternative therapeutic targets will facilitate improved treatment strategies and outcomes.

Aims:

1. To develop and validate an IHC panel to facilitate subtyping of TNBC

2. To determine the prognostic impact of TNBC subtypes by assessing clinical features, RFS and OS rates

3. To determine the predictive impact of TNBC subtypes by assessing the sensitivity of TNBC subtypes to differing chemotherapy regimens

4. Ultimately to identify new molecular targets to individualise treatment strategies for TNBC

Methods:

In order to identify TNBC subtypes on FFPE tissue, an 8-protein IHC protein panel has been developed based on genes enriched in the 6 TNBC subtypes.

IHC Protein PanelProteinBL1BL2IMMMSLLARAR-----++MYC++-++/---TIE1------Bcl2--+-+-PDGFC-++-+++-MMP2-++-+++-RAD21++-+/-+/---IL2R--++-+/--

A tissue microarray has been constructed of 301 TNBCs diagnosed from 1999–2014. To date, 196 cases have been stained and scored for androgen receptor (AR) and 199 cases for Bcl2. A database has been constructed incorporating clinical data with pathological and outcome data.

Results:

n=301 AR+Bcl2Ki67 &gt;10%p53+n30120114121116%10010577361    Median 35-40% Median Age5565545456Range24-9237-9229-8429-9129-92Family History     n836353232%27.530312628BRCA Mutation160453BRCA111-232BRCA24-221NACT611141311CR22-11-PR33111118SD2-1-1POD41112Mets at Dx     n92222%3101.751.651.75Recurrence     n674272728%2220242224Median TTP20.530.5342625Range2-20012-349-2003-2002-95Median OS3944.5342625Range1-3261-1362-3261-3261-163

On initial observation, AR+ TNBCs were diagnosed at an older age than other TNBCs (65 v 55), were less likely to have BRCA mutations, more likely to be metastatic at diagnosis and were associated with longer median OS (44.5 mos). 21% of AR+ cases were Bcl2+. 45% of AR positive cases had Ki67 &lt;10%.

Bcl2+ TNBCs had low rates of metastatic disease at diagnosis and had the longest median time to progression (34 mos). TNBCs with high Ki67 had the shortest median overall survival (31.5 mos).

We propose that at the time of presentation, the entire IHC panel will be stained and scored. Statistical analysis will assess the association of TNBC subtypes on clinicopathological features as well as the impact of subtype on chemotherapy response. Final analysis will also include duration of treatment response, DFS and OS. Our aim is that this study will prognostically and predictively subtype TNBCs so that clinical decision making, therapeutic strategies and patient outcomes can be improved.

Citation Format: Walsh EM, Shalaby A, Murillo LS, Webber MJ, Kerin MJ, Glynn SA, Callagy GM, Ingoldsby H, Keane MM. Subtyping of triple negative breast cancer by a novel immunohistochemistry panel: Assessing the correlation between subtypes and clinical outcomes. [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 P6-05-09.