Immunohistochemical Predictors of Bone Metastases in Breast Cancer Patients.

Bones are the most common metastatic site of relapse in breast cancer patients and the prediction of bone metastases (BM) risk might prompt developing preventive and therapeutic strategies. The aim of the study was to correlate immunohistochemical (IHC) expression of selected proteins in primary breast cancer with the occurrence of BM. We analyzed expression of proteins potentially associated with BM in primary tumors of 184 patients with metastatic breast cancer (113 with- and 71 without BM). Expression of estrogen receptor (ER) in primary tumor was more common in patients with- compared to those without BM (74 vs. 45 % respectively, p = 0.0001), whereas in this subset less common was expression of parathyroid hormone related protein receptor type 1 (16 vs. 34 %, respectively, p = 0.007) and cytoplasmic expression of osteopontin (OPNcyt; 1.9 vs. 14 %, respectively, p = 0.002). The relationship between expression of ER and OPNcyt and the occurrence of BM was confirmed in the multivariate analysis. The ER-positive/OPNcyt negative phenotype was significantly more common in patients with- compared to those without BM (75 and 25 %, p < 0.0001, respectively; HR 1.79, p = 0.013). Luminal A (43 vs. 23 % respectively, p = 0.009) and luminal B/HER2-positive (16 vs. 4.9 % respectively, p = 0.032) subtypes were more common in patients with- compared to those without BM, whereas triple negative breast cancer subtype was less common (16 vs. 38 %, p = 0.002).

Immunohistochemical prediction of brain metastases in patients with advanced breast cancer: the role of Rad51.

BACKGROUND: There are no clinically useful biomarkers predictive of brain metastases (BM) in breast cancer. In this study, we investigated the correlation between expression of selected proteins in the primary tumor and the risk of BM in patients with metastatic breast cancer (MBC). METHODS: The study included 198 MBC patients (96 with and 102 without BM). Using tissue microarrays derived from the primary tumor, we assessed by immunohistochemical expression of ER, PR, HER2, Ki-67, CK5/6, EGFR, HER3, CXCR4, Rad51, E-cadherin, and claudin 3 and 4. RESULTS: Ki-67 ≥14% (hazard ratio [HR] 2.76; P < 0.001), cytoplasmic expression of Rad51 (HR 1.87; P = 0.014) and ER-negativity (HR 1.72; P = 0.029) were associated with increased risk of BM in the multivariate analysis. A three-biomarker profile including ER, Ki-67 and Rad51 vs. other subtypes combined yielded an HR of 4.43 (P < 0.001). CONCLUSIONS: ER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.

Combined treatment with cytoprotective agents and radiotherapy.

Radiotherapy is associated with several toxicities affecting healthy tissues. One of the strategies aimed at decreasing radiation toxicity is the use of radioprotective agents, such as amifostine and palifermin, or factors stimulating hemopoetic stem cells (colony stimulating factors, CSFs): granulocyte-CSF, granulocyte macrophage-CSF and recombinant erythropoetins. The potential beneficial effect of these substances demonstrated in preclinical in vitro and in vivo studies led to numerous clinical trials. This review addresses the current experience on the use of cytoprotective agents in combination with radiotherapy, with particular focus on the safety of these approaches. Despite a relatively large body of literature data, the role of cytoprotective agents combined with radiotherapy remains controversial. Overall, their use in this application is still limited due to modest radioprotective effect for normal tissues, potential risk of tumor protection and increased treatment toxicity. The use of erythropoetins in combination with radiotherapy should generally be discouraged, whereas the safe and effective application of other agents warrants further investigations.