The treatment of advanced, metastatic breast cancer is largely palliative. For most physicians, quality-of-life issues are paramount when choosing which type of therapy is offered. In patients with locally advanced disease in conjunction with distant metastasis, palliative radiotherapy may be advised to control pain or avoid pathologic fractures. This approach is best exemplified in the treatment of isolated bone metastases, chest wall recurrences, brain metastases, and spinal cord compression.
Systemic disease may be controlled by hormonal or cytotoxic therapy. Because the quality of life during an endocrine-induced remission is usually superior to one following cytotoxic chemotherapy, it is preferable to try endocrine manipulation first. As many as one-third of patients with disseminated disease respond favorably to either functional end-organ ablation (ovary, pituitary, adrenal glands) or administration of drugs that block hormonal function. For patients with estrogen receptor–positive tumors, this response rate may be as high as 60%.
Because only 5% to 10% of women with estrogen receptor–negative cancers respond to endocrine treatment, they should not routinely receive hormonal therapy except in unusual cases, such as elderly women who are intolerant of cytotoxic therapy (116).
Cytotoxic chemotherapy should be considered for the treatment of metastatic breast cancer if organ involvement is potentially life-threatening (brain, lung, or liver), if hormonal treatment is unsuccessful, if the disease has progressed after an initial response to endocrine manipulation, or if the tumor is estrogen receptor–negative. The most useful single chemotherapeutic agent is an anthracycline such as doxorubicin, which has an estimated response rate of 40% to 50%. Combination therapy using multiple agents has response rates as high as 60% to 80% (117). Clinical trials, including those investigating the use of trastuzumab for Her-2/neu-positive women with metastases, are underway to examine a variety of combinations for stage IV disease. In Her-2/neu-positive women, the trastuzumab and vinorelbine or taxane (TRAVIOTA) study showed that both regimens were active as first-line treatments for metastatic breast cancer (118). The historically prominent side effects of debilitating nausea and vomiting are well controlled with central-acting antiemetics. The importance of controlling these potentially devastating symptoms cannot be overemphasized.
Bisphosphonates have played an increasing role in the treatment of breast cancer that has metastasized to bone. Zoledronic acid (Zometa) was found to be superior to pamidronate (Aredia) in patients with breast cancer, with a relative risk reduction of skeletal-related events, defined as pathological fracture, spinal cord compression, radiation therapy, or surgery to bone, by an additional 16% (119). A review that compared all oral and intravenous bisphosphonates that were approved for breast cancer treatment in 2005 demonstrated a 41% risk reduction in skeletal related events with zoledronic acid versus placebo, compared with a 14% to 23% risk reduction for ibandronate (Boniva), clodronate, and pamidronate (120). Bisphosphonates may be important in preventing bone loss during hormone-based therapies for breast cancer. Bisphosphonates garnered interest as a possible adjuvant treatment for breast cancer, with early trials showing a decrease in breast cancer recurrence. Further investigations in randomized, controlled trials, including a trial by the Southwest Oncology Group, are comparing stages I through III breast cancer patients randomized to three different bisphosphonates prescribed after adjuvant systemic antitumor treatment.