Management of metastatic breast cancer

♦ Aim is palliation

♦ If hormone-sensitive, bony disease—may survive years

♦ visceral ER-negative disease has bad prognosis

♦ Rare sites—choroid, pituitary

Endocrine therapy

Treatment with tamoxifen, ovarian ablation, progestins, or aromatase inhibitors will provide an objective response in 30% of women with advanced disease, and in 50-60% of those with ER-positive tumours. Disease that responds to endocrine therapy and then progresses has a 25% response rate with second-line treatment; the response to a third agent is 10-15%.

Chemotherapy

Advanced breast cancer is moderately chemosensitive. Active agents include:

♦ Anthracyclines

♦ Alkylating agents

♦ Antimetabolities

Combinations such as FAC (5-fluorouracil, doxorubicin, cyclophosphamide) produce response rates of 40-60%, with a median time to progression of around 8 months. Despite the toxicity of such combinations (alopecia, nausea, mucositis, lethargy, myelosuppression) it has been shown that the quality of life of women improves as they respond to treatment.

25-50% of women respond to second-line chemotherapy with a taxane and studies are currently evaluating the promising combination of anthracycline plus taxane as first-line chemotherapy. Although Phase II studies have suggested that high-dose chemotherapy may produce durable remissions from metastatic breast cancer, no survival benefit has yet been proven for such treatment.

Radiotherapy

Low-dose radiotherapy provides effective palliation for painful bone metastases, soft tissue disease, and spread to sites such as the brain and choroid.

Bisphosphonates

These agents are the mainstays of treatment for malignant hyper-calcaemia. In addition, they can produce healing of some osteolytic metastases and prolonged treatment with bisphosphonates for bone metastases from breast cancer reduces osteolysis, improves bone pain, and prevents hypercalcaemia and fractures. Recent data suggest that prophylactic treatment with these agents may prevent the future development of bone metastases in women with high-risk early breast cancer.

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