Role of Bone Scintigraphy and Tumor Marker-Ca 15-3 in Detection of Bone Metastases in Patients with Breast Cancer

Breast cancer is one of the most frequent types of cancer aff ecting women. After hematogenous spreading of cancer, axial skeleton is most frequently involved. Bone scintigraphy is commonly performed in detection and evaluation of bone metastases. In breast cancer, marker Ca - is widely accepted in follow-up and detection of disease recurrence. Aim of the study was to correlate levels of tumor marker Ca - and presence of bone metastases detected by bone scintigraphy. Study included  patients with breast cancer, previously surgically treated. All patients underwent total body scintigraphy. Ca - was measured by radioimmunoassay. Presence, number and location of bone metastases were correlated with Ca - levels. Bone scintigraphy revealed bone metastases in  () patients.  () patients with metastases and  patient () without scintigraphically visible metastases had elevated Ca - levels. Signifi cant diff erence in distribution of metastases was found for spine (t=., p=.). Correlation between intensity of radiopharmaceutical uptake and level of Ca - in patients was positive (r =.). A weak correlation was found between number of metastases and level of Ca - (r=.). Signifi cant diff erences in Ca - level was found in patients with metastases compared to patients without metastases (chi square , p =.). Since no signifi cant correlation was found between level of Ca - and number of metastases, we consider scintigraphy an appropriate method for assessment of bone metastases in breast cancer.


Introduction
Breast cancer is one of the most frequent types of cancer aff ecting women with incidence peak between age - (,).Th e most common site of distant metastases is skeleton, which is aff ected in about  of all patients.
After hematogenous spreading of cancer, axial skeleton is most frequently involved with pattern that resembles red bone marrow distribution.
Complications associated with skeletal metastases including pain, pathological fractures, hypercalcemia, myelosupresion, spinal and cord compresion, lessions of nerve roots, are demanding for patients and health care resources in general (,) Early detection of bone metastases is mandatory in the evaluation and managament of these patients.
In diagnosis of breast cancer metastases several procedures and tests are available such as: tumor markers (CEA, Ca -), x-rays, CT scan, magnetic resonant imaging, bone scintigraphy.These investigations aim to establish location of dissemination, make a specifi c diagnosis, prevent complications by early diagnosis and fi nally to assess patients response to treatment ().
Although not the latest method, bone scintigraphy is still often requested and commonly performed in detection and evaluation of bone metastases.Th is investigation allows highly sensitive detection of osteoblastic activity.
Tumor markers are present in healthy individuals as well as in patients with malignant diseases but in diff erent concentrations.In breast cancer, breast-associated mucin marker Ca - is widely accepted as a serum tumor marker in follow-up and detection of disease recurrence (,).Th is study was undertaken in order to correlate levels of tumor marker Ca - and presence of bone metastases detected by bone scintigraphy.

Patients and Methods
 patients with pathologically verifi ed and previously surgically treated breast cancer were included in study.All patients underwent total body scintigraphy using double-head gamma camera equipped with low energy high resolution collimator  hours after I.V. injection of MBq Tc-m MDP (methylen diphosponate).
Ca - was measured by radioimmunoassay using microparticle Enzyme-Immunoassay technology (MEIA, Abbott AXSYM system).Presence and number of bone metastases together with their location were correlated with levels of Ca - tumor marker.Statistical analyses were performed with chi-square test, Student t-test, standard deviation.Study was approved by Ethical Committee and informed consent in written was obtained from all subjects in advance.

Results
Median age of patients included in study was  varying from  to .  patients () had pathologically verifi ed cancer on the left breast, the rest of  patients () had the right breast cancer.Bone scintigraphy revealed bone metastases in  () patients.Scintigraphy was negative for metastases in  () patients. patients () with scintigraphically proven metastases and  patient () without scintigraphically visible metastases had elevated Ca - marker.In  patients with normal scintigraphy () only  patient () had elevated Ca - marker, (Table 

.).
Multiple bone metastases were found in  () patients.Four patients () had solitary bone metastases.Analyzing the distribution of bone metastases the highest frequency was found for spine (. of all metastases).
Th e diff erence is signifi cantly higher compared to other bones, (t=.,p=.),Graph .Th e most intensive radiopharmaceutical uptake was found in spine (score -).Diff erence was signifi cant (t=.,p=.),Graph .Correlation between the intensity of radiopharmaceutical uptake and level of Ca - in patients with breast cancer was positive (r=.).Graph .
A weak correlation was found between number of metastases and level of Ca - (r=.)-Graph.However, statistically signifi cant correlation in level of Ca- was found in patients with bone metastases revealed scintigraphically in relation to patients without bone metastases (chi square , p=.)

Discussion
Breast cancer is the leading cause of death in women aged - ().Although bone scan is frequently performed in evaluation of breast cancer metastases, precise role of bone scanning at different stages of the disease is still contentious.Clinical areas in which the bone scan has been evaluated include staging, systematic follow-up of asimptomatic patients, and assessment of response to therapy.In breast cancer, metastases are most often distributed in the axial skeleton, refl ecting the distribution of red bone marrow, with the vertebrae being the most commonly involved site ().In our study, most common site of bone metastases was spine.
Tumor markers sensitivity is also related to the site of recurrence, with the lowest sensitivity for locoregional relapse and highest for liver metastases ().Th e disease extent of patients with bone metastases correlated signifi cantly with elevated Ca - levels.Higher Ca - levels were found for larger disease extent.Consequently, longer survival was observed in patients with limited disease extent ().In our study we found signifi cantly higher levels of Ca - in patients with bone metastases, however, we found no significant correlation between level of Ca - and number of bone metastases.