Bone metastases

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The bone is the most common site of breast cancer metastasis, with a typical clinical presentation of the new development and onset of bone pain. Through poorly understood mechanisms, breast cancer cells are able to induce osteoclastic activity that results in the destruction of the bony cortex and marrow with subsequent increased propensity for pathological fractures as the bony matrix is weakened (19, 20). Although pathological fractures can develop anywhere within the bony structures, breast cancer has a propensity to metastasize to the spine, long bones, and joints (21). It is likely that breast cancer cells metastasize regularly to the bone marrow, with several investigators able to isolate and identify such cells in 13-43% of early and 40-60% of late stage breast cancer patients (22-24). Additionally, others have shown that tumor cells can be readily identified in the peripheral blood, as well as, within the bone marrow, paralleling significant differences in clinical outcomes when found (24-26).

Skeletal breast cancer metastases may be fairly indolent in many instances, with many patients exhibiting minimal symptoms throughout their clinical course. Isolated lesions tend to respond well to hormonal therapy, chemotherapy, and radiation therapy with overall longer survival noted in these patients (27). For example, bisphosphonate therapy for metastatic bone disease has become an effective part of the treatment regimen, providing a durable reduction in the overall frequency of skeletal-related events and symptomatic and palliative relief of metastatic bone pain (28, 29). A comparison was performed between solitary and multiple skeletal metastatic lesions in 703 metastatic breast cancer patients, revealing that 41% had solitary skeletal metastasis and 59% with multiple metastases (27). They show that the sternum is the most common site of solitary metastasis and the thoracic spine and ribs as the most common site for multiple metastases. Radiotherapy also may play an important role in palliation of painful bone metastases (30).

Surgical intervention for metastatic breast cancer to the bone is usually reserved for either the fixation of pathologic fractures, stabilization of weight-bearing bones with impending fractures, or for acute spinal cord compressions which may result in life-threatening or significant functional neurologic compromise that can lead to bowel or urinary incontinence (31, 32). It is estimated that 5% of all cancer patients will develop metastatic spinal cord compression during the course of their disease, with urgent treatment required in most cases (33-35). Breast cancer patients however seem to have an improved median survival compared to other tumor histologies, with long course radiotherapy as the preferred modality of treatment (34). Surgical decompression of the affected segment has only a limited role in acute management, with the preferred immediate treatment being radiotherapy in most cases (34-36).

The sternum is the most common site of isolated bony metastasis (27), with several reported cases of large primary breast cancers capable of extending into the sternum or local recurrences extensively involving the sternum (37-40). When sternal resection of metastatic disease is undertaken with potentially curative intent, consideration should be given to the complexity of the reconstructive options available, such as the combined use of autologous tissue transplants and synthetic mesh (Marlex with or without methylmethacrylate) (2, 41-43). These complex and potentially morbid procedures can occasionally result in long-term survivors, with several studies showing a durable median survival of ~30 months with many patients surviving >6 years (27, 37-43).

Locoregional recurrence of breast cancer involving the chest wall can be found in about 5-40% of patients and is generally thought to have a poor overall prognosis and outcome (44). However, a subgroup of patients may exist that will benefit from an aggressive surgical approach to therapy, with survival greatly influenced by numerous factors, such as the disease-free interval between mastectomy and chest-wall recurrence, primary tumor size, axillary nodal status, and number of recurrences (45). A study by Chagpar et al. examined 130 patients with isolated chest-wall recurrences following mastectomy, showing 5- and 10-year survival rates of 47% and 29%, respectively (44). The significant factors associated with a worse overall survival were positive initial node status, lack of radiotherapy for the treatment of chest-wall recurrence, and use of systemic therapy for treatment of the primary tumor.

Full-thickness chest-wall resection for locally recurrent breast cancer can provide long-term palliation and occasional cure for select patients. Pameijer et al. performed such resections with reconstruction in 22 women with isolated chest-wall recurrences from breast cancer, reporting a 5-year disease-free survival of 67% and an overall survival of 71% (46). Others have performed similar chest-wall resections with complex plastic reconstruction report similar survival rates, ranging from 47% to 62% (47, 48). Complex chest wall reconstruction will usually involve radical resection of chest-wall disease to negative margins when possible, followed by reconstruction with autologous tissue or synthetic mesh and/or methylmethacrylate to fill the defect. Advanced techniques involve the use of extended and V-Y latissimus dorsi myocutaneous flap reconstruction, rectus abdominus myocutaneous flap reconstruction, and cutaneous thoraco-abdominal flaps to cover very large defects up to 600 cm2 (49-51).

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