Screening Of Bone Metastases

Although most patients with advanced breast cancer develop bone metastases, the associated risk factors have not been clearly identified. Therefore, there is no clear consensus regarding when to screen for bone metastases from breast cancer. Current American Society of Clinical Oncology (ASCO) guidelines do not recommend routine bone scan surveillance (14), whereas the National Comprehensive Cancer Network (NCCN) guidelines state that bone scans are recommended for patients with stage III or IV breast cancer but are optional for patients with stage I or II breast cancer (15). The NCCN guidelines also state that for posttherapy surveillance and follow-up, routine bone scans provide no advantages in survival or pain relief for asymptomatic patients and are not recommended (15).

There is also no consensus on the optimal imaging modality for screening of bone metastases in patients with breast cancer. An expert panel performed a literature-based review evaluating current imaging modalities in terms of statistical strength of study design and scientific strength of assessed endpoints (16). Based on the resulting algorithm, skeletal scintigraphy should be the first choice for screening, and confirmation of diagnosis should be made with plain radiography, computed tomography, or magnetic resonance imaging (Figure 2) (16). Use of routine positron emission tomography scanning outside the clinical trial setting was not supported by the literature (16).

No studies of biochemical markers have been able to diagnose or predict the development of bone metastasis, although several markers are being evaluated as possible predictors of bone metastasis. A recent study indicated a significant linear association between urinary levels of alpha C-telopeptide (CTX) and number of bone metastases (P < 0.001) in patients with breast cancer (N = 90) (17). At this time, no marker has clearly demonstrated a predictive correlation. Therefore, the use of bone markers in screening for bone metastases and patient response to therapy is not recommended outside the context of a clinical trial.

Figure 2. Algorithm for detection of bone metastases. *Bone biopsy may be required for confirmation. ^Indications for CT versus MRI are not well defined. In general, CT is indicated for lesions in weight-bearing or chest-wall bones, and MRI is indicated for spinal lesions. XR = Plain radiography; CT = Computed tomography; MRI = Magnetic resonance imaging; SS = Skeletal scintigraphy. Adapted with permission from Hamaoka T, et al. Bone imaging in metastatic breast cancer. J Clin Oncol 2004, 22(14):2942-2953. Reprinted with permission from the American Society of Clinical Oncology (16).

Figure 2. Algorithm for detection of bone metastases. *Bone biopsy may be required for confirmation. ^Indications for CT versus MRI are not well defined. In general, CT is indicated for lesions in weight-bearing or chest-wall bones, and MRI is indicated for spinal lesions. XR = Plain radiography; CT = Computed tomography; MRI = Magnetic resonance imaging; SS = Skeletal scintigraphy. Adapted with permission from Hamaoka T, et al. Bone imaging in metastatic breast cancer. J Clin Oncol 2004, 22(14):2942-2953. Reprinted with permission from the American Society of Clinical Oncology (16).

Although many physicians might not consider screening for bone metastases in patients with no distant metastases from breast cancer and no symptoms of bone metastases, earlier diagnosis of skeletal lesions could provide important benefits. For example, treatment with bisphosphonates has been shown to significantly delay the onset of potentially debilitating SREs, including pathologic fractures (18). Pathologic fractures typically cannot heal without intervention, and may require extended convalescence.

Moreover, pathologic fractures were associated with significant reductions in survival in patients with advanced breast cancer in a recent exploratory analysis of a phase III clinical trial database (11). Delaying the onset of SREs may preserve functional independence and may possibly provide survival benefits. Therefore, defining tools to aid in the early diagnosis of bone metastasis is critical.

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