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Prognostic Value of Receptors for Insulin-like Growth Factor 1, Somatostatin, and Epidermal Growth Factor in Human Breast Cancer¹

Division of Endocrine Oncology (Biochemistry and Endocrinology) [J. A. F., H. P., A. M. A. C. T., J. A-F., J. G. M. K.] and Department of Statistics [W. L. J. v. P.], Dr. Daniel den Hoed Cancer Center, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands, and Sandoz Research Institute Berne, CH 3001 Berne, Switzerland [J-C. R.]

The prognostic significance, as well as the relationship with known prognostic factors in breast cancer, of insulin-like growth factor 1 receptor (IGF-1-R), epidermal growth factor receptor (EGF-R), and somatostatin receptor (SS-R) was evaluated. IGF-1-R was positively correlated with estrogen receptor and age, but not significantly with progesterone receptor, lymph node status, and tumor size. EGF-R was negatively correlated to estrogen receptor and progesterone receptor, whereas no association was found with age, lymph node status, and tumor size. The levels of the tumor contents of IGF-1-R and EGF-R were not significantly related to tumor recurrence in 214 patients (test for trend, P = 0.20 and P = 0.08, respectively). However, patients with tumors containing intermediate levels of EGF-R (0.5 to 2.0 fmol/mg of membrane protein) experienced a longer disease-free survival than did patients with tumors possessing lower or higher levels of EGF-R. This effect was most pronounced in the subgroup of patients with positive axillary lymph nodes: 66% disease-free after 5 yr compared with 38% and 46% for the groups with lower and higher EGF-R levels, respectively. The relapse-free survival for patients with tumors containing SS-R (15%) was significantly longer than for patients with SS-R-negative tumors (82% versus 46% disease free after 5 yr, P = 0.04).

Assessment by multivariate analysis showed that lymph node status, tumor size, and differentiation grade were independent prognostic factors for relapse. In the Cox model, estrogen receptor and progesterone receptor were both negatively correlated with tumor recurrence, whereas overall EGF-R and IGF-1-R did not show such a relation.

¹ This work was supported by a grant from The Netherlands Cancer Foundation (Koningin Wilhelmina Fonds, Grant RRTI 88-9).

² To whom requests for reprints should be addressed, at Division of Endocrine Oncology (Biochemistry), Dr. Daniel den Hoed Cancer Center, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands.

Received 2/20/89. Revised 7/13/89. Accepted 9/12/89.