Expression of metalloproteases and their inhibitors in primary tumors and in local recurrences after mastectomy for breast cancer.

AIMS: To investigate the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) in patients who develop local recurrence (LR) after mastectomy. METHODS: We analyzed the expressions of MMP-1, -2, -7, -9, -11, -13, -14, TIMP-1, -2, and -3, using immunohistochemical techniques, in primary tumors from patients without tumoral recurrence (n = 50), patients who developed distant metastasis (n = 50), and from patients who develop LRs (n = 25). LRs of the latter group were also analyzed for MMPs expression. All the patients underwent mastectomy. RESULTS: Score values for all MMPs and TIMPs were significantly higher in primary tumors of patients with distant metastasis. Primary tumors from patients with LR have lower expressions of MMPs and TIMPs compared with those from patients who developed distant metastasis, and with patients without recurrence for some MMPs. Remarkably, however, primary tumors from patients with LR showed significantly higher percentage of TIMP-1 and 2 expression in stromal cells compared to primary tumors from patients with distant metastasis or primary tumors from patients without tumoral progression. Furthermore, LRs had significantly higher MMP-9 expression than their corresponding primary tumors. CONCLUSIONS: Our data indicate differences in MMPs/TIMPs expression between primary tumors of patients with LRs and of those with distant metastasis, both after mastectomy for breast cancer.

Local recurrence after mastectomy for breast cancer: analysis of clinicopathological, biological and prognostic characteristics.

BACKGROUND: Despite the increasing use of breast-conserving therapy, modified radical mastectomy retains an important role in primary as well as in salvage treatment of breast cancer. Nevertheless, a significant number of patients will eventually develop a local recurrence (LR). AIMS: To identify the potential prognostic factors at the time of the first isolated LR, and to compare the expression of several parameters of the molecular biology of breast carcinomas by primary tumors and paired isolated LRs. METHODS: We analyzed the medical records from 1,087 women who underwent mastectomy for breast cancer, out of which 98 developed LRs as the first manifestation of tumor progression. We investigated the prognostic value of various classical prognostic factors, at the time of mastectomy as well as when the diagnosis of LR was made. In addition, by using tissue microarrays and immunohistochemical techniques, we analyzed the expression of estrogen (ER), progesterone (PR) and androgen receptors (AR), ki67, p53, c-erbB-2 and apolipoprotein D in primary tumors and paired isolated LRs from a subset of patients (n = 25). RESULTS: Patients who developed distant metastases as well as patients with local recurrent disease showed a significantly higher percentage of larger tumors, node-positive status and higher tumoral grade than patients without evidence of tumoral recurrence. Furthermore, patients with LR had a better outcome compared with those with distant metastases, although the former received less frequently adjuvant systemic therapy and/or radiotherapy. Tumor size, histological grade, ER and PR status, and a shorter disease-free interval (<12 months) were significantly associated with overall survival amongst mastectomized patients that developed isolated LR. There was a significant concordance between primary tumors and LRs regarding the expression of the following factors: ER, PR and p53. However, we were not able to demonstrate similar findings for AR, c-erbB-2 and ki67. In addition, ER, PR and p53 status in the LRs were significantly associated with a poorer overall survival. CONCLUSIONS: Based on classical clinicopathological factors as well as on some new biological parameters we have been able to identify subgroups of mastectomized patients with LR differing in their prognosis. Thus, at the present time it would be possible to select group of patients candidates for further and individualized therapeutic strategies.