Correlation of quantitative p95HER2 and HER2 protein expression with pathologic complete response (pCR) in HER2-positive breast cancer patients (pts) treated with neoadjuvant (NEO) trastuzumab-containing therapy

• Published in: Journal of clinical oncology Vol. 30; no. 15_suppl; p. 608
• Main Authors: Villasboas, Jose Caetano, Hurley, Judith, Weidler, Jodi Marie, Paquet, Agnes, Fernandez, Carmen Gomez, Cioffi Lavina, Maureen, Sperinde, Jeff, Chenna, Ahmed, Haddad, Mojgan, Lie, Yolanda, Winslow, John William, Huang, Weidong, Petropoulos, Christos J., Pegram, Mark D.
• Format: Journal Article
• Language: English
• Published: 20.05.2012
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2012.30.15_suppl.608

Abstract only 608 Background: Elevated p95 [HER2-M611-CTF (carboxy-terminal-fragment) also known as p110 or p95HER2] expression has been correlated with poor outcomes in HER2+ pts with metastatic breast cancer treated with trastuzumab (T); however, limited data have been presented on the correlation between p95 and pCR to T in the NEO setting, where p95 was measured by immunohistochemistry. In the current study, we sought to determine whether quantitative p95 and HER2 expression correlated with pCR in pts treated with T + chemotherapy in the NEO setting. Methods: HER2 expression (H2T) was quantified by HERmark in 47 breast tumors using formalin-fixed, paraffin-embedded sections. Tissue remained in 40 cases to measure p95 by VeraTag and compare to a previously published cutoff (Clin Cancer Res 16:4226, 2010). pCR data were available for 45 cases. pCR was defined as the absence of invasive disease in the breast. Results: The overall pCR rate was 46.7% (ER+: 14.3% vs. ER-: 75%; Wilcoxon rank p<0.0001) and was significantly associated with higher H2T levels (p=0.02). In ER- subjects (N=24), no difference in H2T levels was observed between pCR vs non-pCR groups [median H2T=111.5 (IQR 63.4-162.2) vs 150.5 (IQR 43 – 226.2), respectively; p=0.721]. However, within the ER+ group (N=21), H2T levels were significantly higher in the pCR group vs non-pCR group [median H2T=254 (IQR 181.5-584.5) vs 37.3 (IQR 16.4-89); p=0.024]. Using multivariate logistic regression, increasing log(H2T) (p = 0.011), ER-negativity (p = 0.027) and low p95 (p = 0.074) were found to correlate or trend with pCR. Conclusions: pCR was significantly associated with high H2T expression in ER+ HER2+ breast cancer pts who received NEO therapy with T + chemotherapy. A trend towards pCR was seen in tumors that had low p95. These data suggest that quantitative H2T and p95 may provide additional information on response to T-based regimens in breast cancer, particularly ER+ breast cancer. Additional investigation into the possible relationship between quantitative levels of HER2 and p95 expression and T response in the NEO setting in larger cohorts is warranted.