unexpected finding--truncated her2 (p95) does NOT cause herceptin resistance!

[Lani]

unexpected findings are usually the ones we learn the most from!! Should cause them to go back and work harder to find out what makes herceptin work vs be ineffective (de novo or acquired resistance)


Validation of p95 as a predictive marker for trastuzumab-based therapy in primary HER2-positive breast cancer: A translational investigation from the neoadjuvant GeparQuattro study.


Sub-category:
HER2+

Category:
Breast Cancer - HER2/ER

Meeting:
2011 ASCO Annual Meeting

Abstract No:
530

Citation:
J Clin Oncol 29: 2011 (suppl; abstr 530)


Attend this session at the
ASCO Annual Meeting!
Session: Breast Cancer - HER2/ER

Type: Poster Discussion Session

Time: Tuesday June 7, 8:00 AM to 12:00 PM

Location: McCormick Place E450a

Discussion Time: Tuesday June 7, 11:30 AM to 12:30 PM

Location: McCormick Place Arie Crown Theater

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Author(s): S. Loibl, J. Bruey, G. Von Minckwitz, J. B. Huober, M. F. Press, S. Darb-Esfahani, C. Solbach, C. Denkert, H. Tesch, F. Holms, T. N. Fehm, K. Mehta, M. Untch; German Breast Group, Neu-Isenburg, Germany; bioTheranostics, Inc., San Diego, CA; University of Tuebingen and Kantonsspital St. Gallen, St. Gallen, Switzerland; Keck School of Medicine of the University of Southern California, Los Angeles, CA; Charite Universitaetsmedizin, Berlin, Germany; UFK Frankfurt/Main, Frankfurt/Main, Germany; Fachpraxis für Onkologie, Hämatologie und Immunologie, Frankfurt, Germany; Barbaraklinik, Hamm, Germany; Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany; Helios Klinikum Berlin-Buch, Berlin, Germany


Abstract Disclosures


Abstract:

Background: p95 might indicate resistance to trastuzumab (T) (Scaltriti et al. 2007). An immunohistochemical assay has been developed to detect p95, a C-terminal fragment (CTF) of the full-length HER2, by using a monoclonal antibody that specifically recognizes the 611 CTF, the truncated form of HER2 by immunohistochemistry (IHC), and does not recognize total HER2. We investigated p95 as validation in a trial cohort of HER2 positive patients. Methods: 445 patients with HER2+ (locally tested) primary breast cancer received neoadjuvant EC-docetaxel +/-capecitabine concomitant to T in the GeparQuattro study. Tissue microarrays (TMA) from pre-therapeutic core biopsies of 153 patients were available with sufficient tumor tissue on the TMA (>30%) and positive HER2 status centrally confirmed. p95 expression could be assessed with % of positive cells by 3 independent pathologists with a cut-off at 10 (primary analysis), 20 and 30% positive cells on 134 samples. We assessed the pCR rate defined as non invasive residuals in breast and lymph nodes. Resistance was defined as minimal or no microscopic changes in surgically excised tumor tissue (regression grade, RG 0-1 according to Sinn et al). Results: The median age was 49 years (22-78). Clinical T stadium was T1,2,3,4a-c/4d in 3%/70%/11%/8%/8% respectively, 59%/ 41% of these tumors were G2/G3; 51% were hormone receptor (HR) positive. The overall pCR rate was 51% and resistance rate was 32.8%. The pCR rate in the p95 positive tumors (10% cutoff) was 58.2% vs 32.6% in the p95negative group (p=0.009). The resistance rate in the p95 positive group was 25.8% vs 48.7% in the p95 negative group (p=0.014). Results were similar when the cutoff was set at 20% and 30% as well as for clinical response. Conclusions: In contrast to our expectations p95 expression measured by IHC indicates response to neoadjuvant trastuzumab containing treatment in primary HER2 positive breast cancer but not resistance. p95 will be evaluated in whole sections for each patient and data will also be reported. The marker needs to be further validated especially also in the neoadjuvant trials using lapatinib.