Study of distribution of bone metastases in metastatic breast cancer patients compared to other major cancers

Introduction: Metastatic bone disease is frequent in patients with advanced breast cancer. Although it is not specific for the detection of metastatic bony lesions, bone scan is a sensitive method. The pattern of distribution of bone metastases as detected by bone scan combined with clinical data may help in reaching diagnosis. Methods: Technetium-99m-methylene diphosphonate skeletal scintigraphy was used for evaluation of distribution pattern of skeletal metastases in patients with breast carcinoma compared to other common cancers. Results: Out of 134 patients with positive bone scan for skeletal deposits, the primary cancer was breast cancer in 81 patients, prostate in 24, lung in 12, liver in 8, urinary bladder in 6, and head and neck in 3. Few metastases (≤ 3 deposits) were common in breast cancer, while extensive metastatic lesions (≥10 deposits) were more common in prostate cancer (50%). The most common locations of bone metastases in patients with breast cancer were the spine, pelvic bones, femora, and ribs, respectively. In prostate cancer patients, spine was the most common site of metastases, especially the lumber region. In lung cancer patients, thoracic spine was the most common site of metastases, while pelvic bones were the most common site in liver cancer patients. Conclusion: In breast cancer, the most frequent sites of involvement are the spine (especially lumber region), pelvis and axial skeleton, respectively. Spinal and sternal involvements are significantly more in breast cancer than in other malignancies.


Bone scan results were considered negative when:
a) No abnormal increased radiotracer uptake was detected.
b) Radiotracer uptake was characterized by medical and benign disease (e.g.arthritis, fracture and trauma).
Bony metastatic lesions in bone scan films were studied regarding their number and pattern of distribution.
Based on the number of metastatic lesions patients were divided into three categories: To describe the pattern of distribution of bone deposits the involved areas were divided into nine portions: skull, sternum, spine, ribs, pelvic bones, sacrum, humeri, scapulae, femora, tibiae and fibulae and clavicles.
Data were computed using SPSS versions 16 for Windows.Continuous data were expressed as mean ±SD while categorical data were expressed as count and percentage.Student t test was used for comparison of continuous data, while Chi-square test was used for categorical data.P value < 0.05 was considered statistically significant.

RESULTS
From January to June, 2015, a total of 597 patients were referred to the Nuclear Medicine Unit at Menoufia Oncology Department for skeletal scintigraphy.One hundred thirty four patients had histologically-proven malignancies and positive scans for bone deposits.Of these 134 patients with positive bone scan, 81 patients had breast cancer, 24 prostate cancer, 12 lung cancer, 8 liver cancer, 6 urinary bladder cancer and 3 head and neck cancer.Demographic characteristics of patients are shown in table 1.
Table 2 shows the distribution of patients with different primary cancer according to onset of metastases (primary or secondary) and number of metastatic lesions (few, intermediate and extensive).
Table 3 shows the distribution of bone metastases according to the primary cancer site.Table 4 compares the distribution sites of breast cancer patients to other patients.In table 5, the distribution is compared between breast cancer patients with primary skeletal metastases and those with secondary skeletal.

DISCUSSION
It is important for both radiologist and nuclear medicine physician to know the pattern of distribution of metastatic skeletal deposits in breast cancer as it may help them to comment on the nature of lesions within the skeleton.Furthermore, this may aid in expecting the sites of possible skeletal related events and its early management.
Out of the studied 134 patients with positive bone scan for skeletal deposits, 81 cases had breast cancer and 53 cases had other solid malignancies.As regard number of bone metastases, few metastases (≤ 3deposits) were more common in breast cancer patients (45.7%) while extensive metastatic lesions (≥10 deposits) were more common in prostate cancer patients (50%).
As regard the site of bone metastases, the current study showed that the main sites of metastases are the ribs, pelvis and spine.Proximal femora were the most commonly involved sites in the extremities.These results are in agreement with those of Kakhki et al 3 .This can be explained by the fact that sinusoidal vascular spaces in the red bone marrow represent attractive sites for metastases as it is easily penetrated by cancer cells.
The most common location of bone metastases on scan images of patients with breast cancer was the spine, especially the lumber region; which is consistent with the results of Kakhki et al 3 .However, Afzal et al 4 and Wang et al 5 noted that the highest numbers were in the spine, mainly the thoraco-lumbar vertebrae.This is on contrary to our findings, where the lumber vertebrae were the most common metastatic site.
In our study, pelvic bones were the second most common metastatic sites in breast cancer, followed by femora (especially the proximal parts) followed by ribs.While, Kakhki et al 3 reported that the second most common sites in breast cancer patients were the ribs and sternum.Also, Afzal et al 4 and Wang et al 5 reported ribs as the second most common site then pelvic bones.Bieki et al 6 studied the pattern of bone metastases in breast cancer patients and found that the commonest sites were the pelvis and hip, lumbar and thoracic vertebrae and ribs.The difference in distribution between our study and that of other studies may be due to the difference in the number of patients studied.
In prostate cancer, we found the spinal vertebrae as the most common site especially the lumber region; consistent with the results of Kakhki et al 3 .
An explanation for that is the spread of prostatic malignant cells via the Batson venous plexus to the pelvis and spine bones earlier in the course of the disease followed later by other skeletal sites.Similar results were obtained by Wang et al 5 and Zytoon et al 7 who found that metastatic bony lesions of prostate cancer are located mainly in the spine.The second most common metastatic sites in prostate cancer patients in our study were in the pelvic bones, which is in agreement with Kakhki et al 3 and Wang et al 5 .
On the other hand, Zytoon et al 7 found the ribs and femora to be the second and third frequently involved sites.This may be due to the inclusion of relatively few prostatic cancer patients in our study (24 patients) in comparison to Zytoon et al 7 who included 150 patients.Other researchers reported a different pattern of bone metastases in prostate cancer patients.In 2010, Bieki et al 6 reported that the most common sites in prostate cancer patients were pelvis, thoracic vertebrae, proximal femur, ribs and lumbar vertebrae; respectively.
Although, in our study the number of lung cancer patients was small (12 patients), we found that the most common region was thoracic spine mostly due to direct invasion by tumor mass.While, previous researchers found that the ribs then the spinal region were the most common sites 3,8 which can be attributed to direct tumor invasion.
Pelvic bones were the most common site in liver cancer patients; while, upper humeral metastases were the most common in urinary bladder cancer patients.

Conclusions and recommendations
In breast cancer patients, the most common involved bone metastases sites were spine (especially lumber region), pelvic bones and femora; respectively.Compared to other types of cancers, spine, sternum and iliac bone involvement were significantly more common in breast cancer.
Further research investigating the clinical application of studying the pattern of bone metastases is recommended.

Figures 1
Figures 1 to 3 show examples of the studied bone scans.

Figure 1 :
Figure 1: Metastatic breast cancer with extensive bony metastases involving most dorsal and lumber vertebrae, ribs bilaterally pelvic bones and both femora

Figure 2 :
Figure 2: A case of breast cancer with limited metastases

Figure 3 :
Figure 3: Prostate cancer with extensive bone metastases involving both femora, all pelvic bones, lumber and dorsal vertebrae and ribs.

Table 2 :
The onset and number of bone metastases in different cancer types.

Table 3 :
Distribution of bone metastases according to primary cancer.

Table 4 :
Comparison between breast cancer patients and other patients as regard to bone metastases distribution.

Table 5 :
The distribution of bone metastases in breast cancer patients according to the onset of metastases (primary vs. secondary).