herceptin efficacy vs. her2+ breast cancer ABSOLUTE irrespective of PTEN status

[Lani]

I remember years ago Robin P having her tumor tested for PTEN status when deciding whether to push for a year of herceptin, when offered late to those who did not get it adjuvantly in the early trials.

Much has been written about how PTEN status influences herceptin sensitivity/resistance.

Here the previous dogma seems to have been turned on its heels:

J Clin Oncol. 2013 May 6. [Epub ahead of print]

Impact of PTEN Protein Expression on Benefit From Adjuvant Trastuzumab in Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the North Central Cancer Treatment Group N9831 Trial.
Perez EA, Dueck AC, McCullough AE, Chen B, Geiger XJ, Jenkins RB, Lingle WL, Davidson NE, Martino S, Kaufman PA, Kutteh LA, Sledge GW, Harris LN, Gralow JR, Reinholz MM.
Source
Edith A. Perez and Xochiquetzal Geiger, Mayo Clinic, Jacksonville, FL; Amylou C. Dueck and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Beiyun Chen, Robert B. Jenkins, Wilma L. Lingle, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Nancy E. Davidson, University of Pittsburgh Cancer Institute, Pittsburgh, PA; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; Peter A. Kaufman, Dartmouth Hitchcock Medical Center, Lebanon, NH; Leila A. Kutteh, Oncology Associates of Cedar Rapids, Cedar Rapids, IA; George W. Sledge, Indiana University Medical Center Cancer Pavilion, Indianapolis, IN; Lyndsay N. Harris, Yale University, New Haven, CT; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Abstract
PURPOSEIt has been suggested that PTEN, a negative regulator of PI3K/AKT signaling, is involved in tumor sensitivity to trastuzumab. We investigated the association between tumor PTEN protein expression and disease-free survival (DFS) of patients randomly assigned to receive chemotherapy alone (arm A) or chemotherapy with sequential (arm B) or concurrent trastuzumab (arm C) in the phase III early-stage human epidermal growth factor receptor 2 (HER2) -positive trial-North Central Cancer Treatment Group (NCCTG) N9831. PATIENTS AND METHODSThe intensity and percentage of invasive cells with cytoplasmic PTEN staining were determined in tissue microarray sections containing three cores per block (n = 1,286) or in whole tissue sections (WS; n = 516) by using standard immunohistochemistry (138G6 monoclonal antibody). Tumors were considered positive for PTEN (PTEN-positive) if any core or WS had any invasive cells with ≥ 1+ staining. Median follow-up was 6.0 years.ResultsOf 1,802 patients included in this analysis (of 3,505 patients registered to N9831), 1,342 (74%) had PTEN-positive tumors. PTEN positivity was associated with hormone receptor negativity (χ2 P < .001) and nodal positivity (χ2 P = .04). PTEN did not have an impact on DFS within the various arms. Comparing DFS of arm C to arm A, patients with PTEN-positive and PTEN-negative tumors had hazard ratios (HRs) of 0.65 (P = .003) and 0.47 (P = .005), respectively (interaction P = .16). For arm B versus arm A, patients with PTEN-positive and PTEN-negative tumors had HRs of 0.70 (P = .009) and 0.85 (P = .44), respectively (interaction P = .47). CONCLUSIONIn contrast to selected preclinical and limited clinical studies suggesting a decrease in trastuzumab sensitivity in patients with PTEN-negative tumors, our data show benefit of adjuvant trastuzumab for patients with HER2-positive breast cancer, independent of tumor PTEN status.
PMID: 23650412 [PubMed - as supplied by publisher]

[Mandamoo]

Thank you Lani.