Small integrin-binding ligand N-linked glycoproteins (SIBLINGs) constitute a family of extracellular matrix proteins involved in bone homeostasis. Their pattern of expression has been primarily reported in bone and tooth and, more recently, in several cancer types. Dentin matrix protein 1 (DMP1), a SIBLING family member, expression was investigated by immunohistochemistry in a retrospective series of 148 primary human breast cancers. Correlations between DMP1 expression levels in the tumors and clinicopathologic features, bone metastases development and relapse of the disease were examined. DMP1 was expressed by 63.5% of the breast tumors analyzed. Significant inverse associations were found between DMP1 expression levels and the size and grade of the tumors (both, P < 0.0001). High DMP1 expression levels in the primary breast lesions were associated with a lower risk of subsequent development of skeletal metastases (P = 0.009). Patients with tumors expressing high levels of DMP1 had a significantly higher disease-free survival rate than those with low DMP1-expressing tumors (P = 0.0062). When DMP1 expression was examined in breast cancer cell lines, we found that non invasive MCF-7 and T47-D cells expressed higher levels than highly invasive MDA-MB-231 and Hs578T cells. Moreover, the specific inhibition of DMP1 expression in MCF-7 cells using siRNAs promoted significantly their migratory capability. Our data implicate for the first time DMP1 expression in breast cancer progression and bone metastases development.
Background Trastuzumab is indicated for the treatment of patients overexpressing HER2 in metastatic breast cancer and HER-positive early breast cancer. Purpose This study aimed to evaluate the use of trastuzumab in an adjuvant setting, in the Hospital Garcia de Orta. Materials and methods This evaluation, carried out in September 2011, included all early-stage breast cancer patients who started trastuzumab in 2008 or 2009. Data source: medical records and patients' prescriptions from the cytostatic unit in the pharmacy department. Each patient was evaluated on six factors of poor prognosis (age < 50 years; invasion of lymph nodes; absence of oestrogen and progesterone receptors; tumour size > 2 cm; disease staging ≥ GIII and overexpression of the HER2 receptor). Results This study included 32 women with an average age of 49.5±11.4 years (33-75 years). Twenty-five women were clinically well (78.1%), 2 (6.3%) had metastases and 5 (15.6%) died. All patients had at least one factor of poor prognosis (over-expression of HER2). Only 1 patient had 1 poor prognosis factor, 6 had two factors of poor prognosis, 12 patients had 3, 9 patients presented 4 and 4 patients had 5 factors for poor prognosis. Statistically significant differences were found between the patients who were clinically well and those who developed metastatic disease or died, for the number of poor prognosis factor present at the time of trastuzumab prescription (p<0.05). Of all the poor prognosis factors, disease staging was the one that showed statistically significant differences between the 2 groups of patients (p<0.001). Conclusions The literature refers to disease staging as the most accurate estimate of prognosis in breast cancer. Based in our study, disease staging was also the factor of prognosis that best predicted the result of trastuzumab therapy.
Objective: Resection of the primary tumor in metastatic breast cancer is controversial in literature. Some evidence have suggested that women who undergo resection of the primary metastatic breast cancer achieved improved survival outcomes. The objective of this study is to evaluate the impact of primary tumor resection (PTR) in patients with metastatic breast cancer. Methodology: Literature review. We performed our search in the following databases: Medical Literature Analysis and Retrieval System Online (MEDLINE), Wiley Online Library, Scopus, and PubMed Central (PMC). Eight studies from 2016-2019, including randomized controlled trials, meta-analysis, and systematic reviews were selected. Results: Although there are some polemic opinions about the surgical treatment, the latest studies that we have analyzed emphasized that PTR is associated with better prognosis in women with metastatic breast cancer. In most studies, it was reported in literature that progression-free survival (PFS) is better on those who underwent surgery. In addition, primary tumor resection has been reported to be associated with longer progression-free survival at a distance (Hazard Ratios 0.42). Improved survival was even associated with surgery regardless of tumor size. An expert group of oncologists from India came to a consensus that surgery for primary tumor should be done in patients with oligometastatic breast cancer. A similar conclusion was reached by a research group in Mexico, who suggest that PTR has a positive impact on women PFS and borderline overall survival, particularly benefiting those with oligomethasic disease. Primary tumor resection was also associated with a longer median overall survival (OS). On a study conducted in USA, which included 29,916 patients with metastatic breast cancer, 15,129 (51%) underwent primary tumor resection, and 14,787 (49%) patients did not undergo surgery. OS achieved was 34 vs 18 months, in favor of surgical patients. A retrospective cohort study in USA registered survival of at least 10 years seen in 9.6% (n=353) and 2.9% (n=107) of those who did and did not receive surgery, respectively. Additionally, those undergoing surgery had longer median survival than those who did not (28 months vs 19 months). In women with de novo stage IV breast cancer, current studies show that surgical resection of the primary tumor occurs in almost half of those alive 1 year after diagnosis. However, we acknowledge that there are considerable discussions about the selection of patients, since most studies are likely to choose those with good status performance. Conclusion: The primary role of local treatment to the breast in metastatic breast cancer is palliation. Patients with metastatic disease should be evaluated for possible local management of the primary if it may control local complications from the cancer (e.g. bleeding, infection, or wound management). Based in the analysis, primary tumor resection in metastatic breast cancer is associated with higher survival rates, when compared to not surgical gro...
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