[15674769]
Rptr wishes to describe an experience with the dako polyclonal antibody against her2 and the herceptest kit. This device is used as a test to see if breast cancer pt's are eligible for therapy with herceptin. Specifically, caller wishes to report the herceptest and increased incidence of overexpression. See attached letter, that will be published in the journal of clinical oncology. Rptr writes, "to the editor: the her2 oncogene encodes a transmembrane protein, p185, which is considered to function as a growth factor receptor. Her2 protein overexpression has been associated with a poor prognosis in women with breast cancer. Recently, her2 overexpression has assumed therapeutic implications because of the recent fda approval of trastuzumab (herceptin), a humanized monoclonal antibody developed by genetech, inc and directed against her2 protein. Antitumor efficacy for trastuzumab has been identified in women with metastatic breast cancer when used both as a single agent (1) and in combination with chemotherapy (2). The fda has also recently approved an immunohistochemical test kit developed by dako corp, herceptest, that uses a rabbit polyclonal antibody to determine a pt's her2 status. We are writing this letter to communicate our experience with the dako polyclonal antibody in three cohorts of pts. Our results suggest a higher incidence of her2 overexpression with this fda-approved antibody kit than the generally accepted level of 20-30%. We initially tested an intramural mayo cohort of 117 women with primary breast cancer collected between august 1997 and september 1998 with the dako polyclonal antibody. Seventy (60%) of the 117 pts were her2 overexpressors defined as 3+(44 pts, 38%) or 2+ (26 pts, 22%) according to criteria specified by dako for interpretation of staining. Since this frequency of her2 overexpression was several-fold higher than that previously reported, we proceeded to evaluate a separate cohort of pts whose tissue was submitted through a reference laboratory, mayo med laboratory. The extramural cohort consisted of 1142 pts tested between june 1998 and november 1998. All pts were known to have breast cancer but no other clinical data were available as these tissues were submitted for her2 testing only. Her2 overexpression was identified in 651 (57%) of the pts and was 3+ in 340 pts (30%) and 2+ in 311 pts (27%). Because this high level of her2 positivity was observed using the dako her2 antibody and our own detection system, we next compared results in a third cohort of 80 pts with resected node-positive breast cancer that were also assayed with the herceptest kit and the anti-her2 monoclonal antibody cb11. There was a high level of concordance (90%) for positive versus negative overexpression between results obtained with the herceptest and our own staining system using the dako antibody, but a low level of concordance (60%) between the herceptest and the monoclonal cb11. The incidence of her2 overexpression with cb11 was 26% as expected. However, thirty-two (54%) of the fifty-nine pts considered her2 negative (ie 0 or 1+) by cb11 were found to be positive (ie 2+ or 3+) with the herceptest. These results indicate a higher frequency of her2 overexpression with the herceptest than would be expected in breast cancer pts. As this antibody system is the only one fda-approved, we report these findings to encourage additional investigation into the sensitivity of the herceptest. "
Patient Sequence No: 1, Text Type: D, B5