Abstract P3-13-03: Molecular factors associated with bone metastases in breast cancer patients
Authors: Winczura P , Sosinska-Mielcarek K , Duchnowska R , Badzio A , Lakomy J , Majewska H , Peksa R , Pieczynska B , Radecka B , Debska S , Zok J , Rogowski W , Strzelecka M , Kulma-Kreft M , Blaszczyk P , Litwiniuk M , Jesien-Lewandowicz E , Rutkowski T , Jaworska-Jankowska M , Adamowicz K , Foszczynska-Kloda M , Biernat W , Jassem J 
Published: August 2014

Abstract
Background. Bones constitute the most frequent localization of distant failure in breast cancer patients. Treatment of bone metastases is virtually palliative, but in a proportion of patients can effectively prolong survival and improve quality of life. Currently, there are no effective strategies to prevent bone dissemination with systemic adjuvant therapies. Thus, better molecular selection and identification of patients who have particularly high risk of skeletal metastases may facilitate designing future clinical trials. In this study we analyzed expression of selected tumor proteins potentially associated with skeletal metastases in breast cancer patients.
Patients and methods. The study group included 184 metastatic breast cancer patients; 113 with clinically diagnosed bone metastases and 71 with exclusively other sites of metastases, respectively. In all patients, using tissue microarrays technology, IHC expression of the following proteins was evaluated in the primary tumor: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, cyclooxygenase 2 (COX2), chemokine receptor CXCR4, osteopontin (OPN), calcium sensing receptor (CaSR), cytokeratins 5/6 (CK5/6) and parathyroid hormone-related protein receptor 1 (PTHrPR1). Additionally based on ER/PR, HER2 and Ki67 expression, following molecular breast cancer subtypes were selected: luminal A, luminal B HER2-negative, luminal B HER2-positive, nonluminal HER2-positive and triple negative.
Results. Median survival in patients with bone vs. other site of metastases was 56 vs. 37 months respectively (p = 0.0098). ER expression was more common in patients who did, compared with those who did not develop bone metastases (74.% vs. 45% respectively; p = 0.0001), whereas cytoplasmic overexpression of OPN (1.9% vs. 14% respectively; p = 0.002) and PTHrPR1 (16% vs. 34% respectively; p = 0.007) was more common in patients with other sites of metastases. The impact of ER and cytoplasmic OPN expression on the risk of bone dissemination was confirmed in the multivariate analysis (Table 1). Luminal A breast cancer subtype (43% vs. 23% respectively; p = 0.009) and luminal B HER2-positive (16% vs. 4.9%, respectively; p = 0.032) were more common among patients with bone dissemination, whereas triple negative tumors prevailed in patients with other sites of metastases (16% vs. 38%; p = 0.002). Median survival of patients with luminal A subtype was significantly longer than that with remaining subtypes (67 vs. 38 months respectively; p = 0.0004).
Conclusions. These results suggest that ER expression and lack of OPN expression are independent factors predicting increased risk of bone dissemination in breast cancer patients. Bone metastases are specifically associated with luminal A and luminal B HER2-positive subtypes.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-03.