Breast Carcinoma Bone Metastases Research Articles

The appearance of breast cancer metastases on dry bone: Implications for forensic anthropology

Breast carcinoma is a major cause of morbidity and mortality in women. The study of bone pathologies presents considerable potential in anthropology, paleopathology, forensic science and medicine. In this paper, we present and discuss metastatic lesions found in the skeletons of known individuals from the CAL Milano Cemetery Skeletal Collection, clinically diagnosed with breast cancer during life. Fourteen skeletons from a contemporary and identified collection were macroscopically studied and metastases were identified by comparison with clinical literature. As a result, bone metastases were observed in 43% of the study sample. They were located most commonly on the ribs (28.1%), pelvic girdle (19.8%), vertebrae (15.6%), skull (15.6%), scapulae (10.2%) as well as proximal segment of the femora (8.4%) and humeri (2.4%) respectively, favoring sites of high vascularization. The majority of the lesions were osteolytic, although osteoblastic and mixed metastases did occur. Osteolytic metastases appear as coalescent porosity or round to oval perforating lesions on bones with denticulated margins and pitted surrounding bone, whereas osteoblastic metastases thickened the existing trabecula (spongiosclerosis). Mixed metastases were perforating lytic lesions exposing the osteoblastic activity in the underlying trabecular bone. These results, consistent with the data from the literature, strengthen the diagnostic criteria for metastases and illustrate the aspect of bone metastases in breast carcinoma.

Multivariate analysis of bone metastases in breast carcinoma

ObjectiveTo investigate the risk factors of bone metastases in breast carcinoma.MethodsBy cross sectional study, the data of 225 breast cancer patients who were inpatients in four hospitals in Hangzhou were analyzed. All patients underwent total body bone scan with single photon emission computed tomography (SPECT) at least once during 1995 to 2000.ResultsAll patients were followed-up to 294 months after operation, bone metastases were found in 113 cases, suspected bone metastases 3 cases, with a bone metastases rate of 50.9% (113/222). Multivariate analysis by Cox’s proportional hazards regression model showed that there were four risk factors of bone metastases in breast cancer: (1) clinical stage, I∼IV stages with a hazard ratio of bone metastases of 1.945, 95% confidence interval 1.396∼2.710; (2) number of invaded axillary lymph nodes, with a hazard ratio of 1.039, 95% confidence interval 1.0142∼1.068; (3) skeletal complications (yes vs. no), with a hazard ratio of bone metastases of 1.722, 95% confidence interval 1.060∼2.796; (4) age at the time of surgery or diagnosis, with a hazard ratio of 2.048, 95% confidence interval 1.123∼3.876 for patients of age 40∼50 y versus patients bellow 40 y of age and 2.837, 95% confidence interval 1.473∼5.465 for patients of age above 50 y versus patients of ages between 40 and 50. Kaplan-Meier curves showed that for patients with more than 5 invasive axillary lymph nodes, compared with those with 1∼5, the bone metastasis rates increased significantly (x2=6.3319, P=0.012).ConclusionThe clinical stage, number of metastatic axillary lymph nodes, age at the time of operation and skeletal complications are essential risk factors of bone metastases.

Mechanisms of osteolytic bone metastases in breast carcinoma.

Osteolytic and osteoblastic metastases are often the cause of considerable morbidity in patients with advanced prostate and breast carcinoma. Breast carcinoma metastasis to bone occurs because bone provides a favorable site for aggressive behavior of metastatic cancer cells. A vicious cycle arises between cancer cells and the bone microenvironment, which is mediated by the production of growth factors such as transforming growth factor beta and insulin growth factor from bone and parathyroid hormone-related protein (PTHrP) produced by tumor cells. Osteolysis and tumor cell accumulation can be interrupted by inhibiting any of these limbs of the vicious cycle. For example, bisphosphonates (e.g., pamidronate, ibandronate, risedronate, clodronate, and zoledronate) inhibit both bone lesions and tumor cell burden in bone in experimental models of breast carcinomametastasis. Neutralizing antibodies to PTHrP, which inhibit PTHrP effects on osteoclastic bone resorption, also reduce osteolytic bone lesions and tumor burden in bone. Other pharmacologic approaches to inhibit PTHrP produced by breast carcinoma cells in the bone microenvironment also produce similar beneficial effects. Identification of the molecular mechanisms responsible for osteolytic metastases is crucial in designing effective therapy for this devastating complication.

Oral bisphosphonates

BACKGROUND This study was conducted to review the efficacy and safety of oral bisphosphonates for the treatment of bone metastases in cancer patients. METHODS Available published clinical studies of oral bisphosphonates in bone metastases from 1980 to the present were identified through a MEDLINE search and from literature references. Data were reviewed for efficacy and safety, with an emphasis on double blind, placebo-controlled studies; clinically relevant endpoints; and appropriate study methodology. RESULTS Etidronate, alendronate, pamidronate, risedronate, and tiludronate currently are available in the U.S. as either intravenous and/or oral formulations. Although newer bisphosphonates are more potent, oral bioavailability remains < 1%. Oral etidronate has been found to be ineffective in patients with multiple myeloma and prostate carcinoma bone metastases. Pamidronate has been found to be effective in reducing skeletal morbidity associated with bone metastases in both multiple myeloma and breast carcinoma patients when given intravenously, but is ineffective orally in multiple myeloma patients. To the authors' knowledge, there are no double blind, placebo-controlled trials of oral pamidronate in patients with breast carcinoma and bone metastases. Several clinical trials with clodronate, a bisphosphonate that is not available in the U.S., have shown mixed results in patients with myeloma and breast carcinoma bone metastases. To the authors' knowledge, there are no published trials evaluating oral alendronate, tiludronate, or risedronate in patients with metastases to bone. CONCLUSIONS Oral bisphosphonates do not appear to be as effective as intravenous administration in reducing skeletal complications in patients with metastases to bone lesions. Low oral bioavailability is the most likely reason for this difference. Oral dosing should not be substituted for intravenous administration in the treatment of malignant osteolysis. Cancer 2000;88:6–14. © 2000 American Cancer Society.

Oral bisphosphonates

This study was conducted to review the efficacy and safety of oral bisphosphonates for the treatment of bone metastases in cancer patients. Available published clinical studies of oral bisphosphonates in bone metastases from 1980 to the present were identified through a MEDLINE search and from literature references. Data were reviewed for efficacy and safety, with an emphasis on double blind, placebo-controlled studies; clinically relevant endpoints; and appropriate study methodology. Etidronate, alendronate, pamidronate, risedronate, and tiludronate currently are available in the U.S. as either intravenous and/or oral formulations. Although newer bisphosphonates are more potent, oral bioavailability remains < 1%. Oral etidronate has been found to be ineffective in patients with multiple myeloma and prostate carcinoma bone metastases. Pamidronate has been found to be effective in reducing skeletal morbidity associated with bone metastases in both multiple myeloma and breast carcinoma patients when given intravenously, but is ineffective orally in multiple myeloma patients. To the authors' knowledge, there are no double blind, placebo-controlled trials of oral pamidronate in patients with breast carcinoma and bone metastases. Several clinical trials with clodronate, a bisphosphonate that is not available in the U.S., have shown mixed results in patients with myeloma and breast carcinoma bone metastases. To the authors' knowledge, there are no published trials evaluating oral alendronate, tiludronate, or risedronate in patients with metastases to bone. Oral bisphosphonates do not appear to be as effective as intravenous administration in reducing skeletal complications in patients with metastases to bone lesions. Low oral bioavailability is the most likely reason for this difference. Oral dosing should not be substituted for intravenous administration in the treatment of malignant osteolysis.

MCA Serum Determination in Breast Carcinoma Patients for the Diagnosis of Bone Metastases

Serum MCA levels were determined in 173 consecutive patients with breast cancer in order to assess the clinical utility of MCA for the detection of bone metastases. Bone pathology was diagnosed by scintigraphy, radiology and clinical follow-up. Metastases were found in 37 patients, benign lesions in 25, and in 111 no bone lesions were found. Eighteen of the 173 bone scans were considered indeterminate for metastases. Based on the receiver-operating characteristic curves (ROC) analysis, the cut-off level for MCA was set at 20 U/ml. Only in 4 of the 37 patients with bone metastases MCA was below 20 U/ml. All 4 patients had completed their chemotherapy course within six months before MCA determination. Only in 6 patients of the 136 without bone metastases MCA levels were above 20 U/ml. Of the 18 patients with indeterminate bone scans, 15 had benign lesions and all of them had MCA levels below 20 U/ml. MCA determination is a sensitive method for the detection of bone metastases in breast carcinoma. We encourage the use of this procedure for the selection of high-risk groups or as a complementary method for the interpretation of bone scintigraphy.