Nothing is ever simple!
Not only is serum Her2neu is increased by ovarian oblation by chemotherapy or leuprorelin injections, but tumor her2neu and Ki67 values depend which phase of the menstrual cycle the primary tumor is removed in. Here is the abstract--full article readable:
1: Breast Cancer Res Treat. 2003 Aug;80(3):245-55.
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Upregulation of HER-2/neu by ovarian ablation: results of a randomized
trial comparing leuprorelin to CMF as adjuvant therapy in node-positive
breast cancer patients.
Luftner D, Jung A, Schmid P, Geppert R, Kienle E, Wernecke KD, Possinger K;
Takeda Adjuvant Breast Cancer Study with Leuprorelin Study Group.
Medizinische Klinik und Poliklinik II, Schwerpunkt Onkologie und
Hamatologie, Universitatsklinikum Charite, Campus Mitte,
Humboldt-Universitat zu Berlin, Berlin,Germany.
Diana.Lueftner@rz.hu-berlin.de
PURPOSE: HER-2/neu oncogene expression is modulated by an
estrogen-sensitive binding site in the HER-2/neu promoter. Utilizing the
circulating antigen of HER-2/neu in serum (sHER-2/neu) as a surrogate marker
we investigated whether ovarian ablation by adjuvant therapy leads to an
upregulation of HER-2/neu in breast cancer patients. PATIENTS AND METHODS:
The analysis was done on sera from premenopausal, node-positive,
hormone-receptor positive patients randomized in a multi-center trial. The
study was designed with patients receiving either 11.25 mg of leuprorelin
s.c. every 3 months over 2 years or CMF chemotherapy for 6 cycles. Sera,
available from 80 patients in the leuprorelin arm and from 53 patients in
the CMF arm, were collected at 0, 3, 6, 12, 18, 24 and 30 months. sHER-2/neu
was measured using a standardized ELISA assay that has an upper limit of
normal of 15 ng/ml. sHER-2/neu results were correlated to the levels of LH,
FSH and estradiol as indicators of ovarian ablation and to the tumor marker,
CA 27.29. RESULTS: During estradiol deprivation, sHER-2/neu levels increased
significantly by more than one third from 8.1 ng/ml to 11.0 ng/ml (p <
0.0001) in both treatment arms. The most pronounced relative increase
occurred within the first 3 months (p < 0.001). In only 2.7% (16/587) of
sHER-2/neu measurements, the sHER-2/neu results were elevated above 15
ng/ml, confirming the upper limit of normal for breast cancer patients
irrespective of their menopausal status. At month 30, the sHER-2/neu level
started to decrease in the leuprorelin arm, reflecting reversible castration
and estradiol reconstitution. Conversely, CA 27.29 levels did not show a
trend over time, indicating that sHER-2/neu changes were of a regulatory
nature and were not merely a reflection of increasing residual disease.
CONCLUSION: Our study demonstrates the upregulation of HER-2/neu during
ovarian ablation. These results are consistent with data showing that the
percentage of HER-2/neu positive tumors, evaluated by standardized
immunohistochemistry on the primary tumor, is significantly increased during
the follicular phase of the menstrual cycle (Balsari et al., Am J Pathol
155: 1543-1547, 1999). Regulatory processes at the HER-2/neu gene should be
considered when prescribing specific therapy for breast cancer.
Publication Types:
• Clinical Trial
• Randomized Controlled Trial
PMID: 14503797 [PubMed - indexed for MEDLIN