Growth and metastasis of surgical specimens of human breast carcinomas in SCID mice.

PURPOSE: We have studied the growth and metastatic potential of surgical specimens of breast carcinomas engrafted into the large abdominal (gonadal) fat pad of severe combined immunodeficient (SCID) mice. We present results of this study, details of the implantation protocol and histologic characterization of several of the tumor xenografts.
MATERIALS AND METHODS: We evaluated the growth within SCID mice of 48 breast carcinoma specimens derived from 46 patients (45 primary breast cancers or local recurrences and 3 regional metastatic lymph nodes) obtained from resected tissues at this Institute over a 3-year period. The growth of each transplant was assessed by histologic examination of the xenografts at various times after implantation or upon passage into additional mice.
RESULTS: We observed that placement of human breast tumors within the gonadal fat pad could result in tumors that grew either rapidly, slowly, or not at all. Of 48 tumors studied, 12 (25%), including one of the three lymph node-derived tumors, grew rapidly enough within some or all of the implanted mice (i.e., the tumors reached a diameter of 2-3 cm within 2-6 months) to allow repeated passage. Metastatic spread to the SCID mouse lung, liver, and/or diaphragm and other sites was observed with the xenografts derived from 8 of these 12 rapidly growing tumors. Tumors in a second category often took from 6 months to over 1 year to only double or triple in size. This slow-growth group consisted of 25 patients' tumors (53%), including the remaining two metastatic lymph node-derived tumors. These xenografts would usually maintain a slow growth rate even upon later passage into new animals. A third category consisted ofpatients' tumors (23%) that failed to grow at all (i.e., no evidence of tumor growth in any of the mice implanted), as discerned by histologic evaluation at various times after implantation. Histologic examination of tumor xenografts and metastatic tumors revealed considerable variation in histopathology among the different patients' tumors. DISCUSSION: Further examination of the heterogeneous properties of primary human breast carcinomas within SCID mice may provide a simple yet valuable new approach for the long-term study of human breast cancer biology. Importantly, use of the protocol described here can often permit the isolation of substantial quantities of human breast cancer cells for biochemical and molecular analyses. The ability to passage patients' breast tumors into large numbers of mice will permit the preclinical testing of new therapies for the treatment and prevention of this disease.