257P - EGFR and p53 expression in androgen receptor (AR)-positive, triple negative breast cancer (TNBC)

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Breast Cancer, Early Stage
Translational Research
Presenter Ayca Gucalp
Authors A. Gucalp1, G. Gupta2, S. Patil3, Y.H. Wen4, M. Akram4, E. Brogi4, S. Powell2, A. Ho2, C. Hudis5, T. Traina5
  • 1Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 2Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 3Biostatistics And Epidemiology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 4Dept Of Pathology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 5Dept Of Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US

Abstract

Background

TNBCs are a heterogeneous group characterized by lack of ER/PR/HER2 expression. Doane et al described a subgroup of TNBC associated with AR-dependent growth. While expression of EGFR and p53 are common in TNBC, their role in AR+ TNBC is less clear. We report the rates of EGFR and p53 expression and clinicopathologic features of AR+ TNBC from a retrospective cohort at MSKCC.

Methods

We identified 1,032 patients (pts) with resectable, TNBC (ER/PR < 1%; HER2 < 2 + /FISH < 2) who had surgery at MSKCC (1998-2006). Exclusions: neoadjuvant chemotherapy, prior XRT, inflammatory/metastatic BC. TMAs were constructed from 210 readily available primary tumors (> 1 cm) with each tumor represented by 3 cores. AR was tested with DAKO Clone AR441, dilution (dil) 1:500; ratio of DAB nuclear staining to hematoxylin signal >1 SD above mean was defined as AR+. EGFR and p53 were tested with Thermo-Scientific Clone EP38Y, dil 1:50 and DAKO Clone D07, dil 1:50 respectively. Scoring: 0-1+ negative, 2-3+ positive. Fisher's exact test used to evaluate correlation between AR with EGFR and p53. RFS and OS evaluated using Kaplan-Meier methods. Clinicopathologic variables by AR status were compared using Chi-square/t-tests.

Results

166 pts had adequate cores for AR testing. 10% were AR+ (17/166). 160 pts were evaluable for EGFR and 164 pts for p53. Median (med) followup: AR + =6 years (y), AR- = 5.6y. Adjuvant chemotherapy received: AR+ 82%, AR- 87%, P = 0.40. EGFR was expressed more frequently in AR- than AR+ TNBCs (111/143 (78%) vs 9/17 (53%); P =0.04). p53 expression was similar in AR- and AR+ TNBC (82/147 (56%) vs 7/17 (41%); P =0.30). Clinicopathologic variables based on AR and EGFR status appeared similar. 3y RFS and OS data are below.

Conclusion

Consistent with published reports, loss of AR expression correlates with EGFR expression. In contrast, no association was observed with p53 and AR. These data are hypothesis generating regarding the mechanism of interaction of AR and EGFR in TNBC.

-3 year RFS (95% CI) -3 year OS (95% CI)
AR+ 76% (47-90) 88% (59-97)
AR- 81% (74-87) 93% (87-96)
AR+ EGFR+ (n = 9) 67% (39-98) 78% (36-94)
AR+ EGFR- (n = 8) 88% (39-98) 100%
AR- EGFR+ (n = 111) 82% (73-88) 91% (84-95)
AR_ EGFR- (n = 32) 81% (61-92) 97% (80-100)

Disclosure

All authors have declared no conflicts of interest.