Treatments for High-Risk and Metastatic Breast Cancer

In recent years, more aggressive treatments for locally advanced breast cancer have come into broad use and have shown significant benefit for some Stage III patients. Neo-adjuvant chemotherapy, where combination chemotherapy is administered prior to surgery, is often followed, in cases of extensive axillary node involvement, with a course of post-mastectomy radiation to the chest wall and underarm area, sometimes extending to the upper chest. More frequent and higher doses of chemotherapy drugs have been made tolerable by several new drugs used in supportive care, including marrow-stimulating drugs like G-CSF (filgrastim) and erythropoietin. In clinical trials, these enhanced treatments have shown somewhat better progression-free survival, and may affect long-term survival as well. This is in part made possible by radiation techniques that do a better job of sparing the heart, large vessels, and lungs, although longer-term damage cannot be ruled out.

For the woman with locally advanced breast cancer, the best chance for survival or long-term remission will usually lie in immediate, aggressive chemotherapy, followed by surgery and radiation, and then more chemotherapy. For her, time is of the essence, since delays in treatment can lead to higher rates of recurrence. If she is to complete the rigorous chemotherapy regimen that has been recommended, she will need good supportive care, especially the latest in expensive growth-factor support and anti-nausea medications. After her treatment has been completed, she will need to be seen by her oncologist on a regular basis, and symptoms that might herald a recurrence evaluated.

It should be emphasized in this introductory section that such complex, intensive treatments are costly, resourceintensive, and certainly require motivated patients with good support networks.

When breast cancer spreads through the bloodstream to other parts of the body, this is described as "distant metastasis." Nearly any tissue in the body may be affected, but the bones, liver, lungs, soft tissue (including regional lymph nodes), and brain are the most common sites for breast cancer metastasis. Lobular breast cancer, which has a different pattern of recurrence, with an affinity to spread to the lining of the viscera, can be extremely difficult to detect.

At Stage IV, the disease is no longer considered curable, with the exception of the estimated 1-3 percent of patients who, for unknown reasons, experience longterm survival with stable disease or complete remission following treatment. However, even when the disease does continue to spread, metastatic breast cancer can often be treated as a chronic disease for a number of years. Until very recently, estimated mean survival time for women diagnosed at Stage IV or with distant metastatic recurrence was about one to three years, but with improvements in care, including a number of new non-cross resistant treatment alternatives that have been approved by the FDA since the mid-1990s, survival time with metastatic disease appears to have increased significantly.

A recent study from M.D. Anderson Cancer Center13 that compared length of survival of metastatic breast cancer patients treated at their institution in five-year increments, found that median survival had doubled to 51 months (range 33-69 months) in 1995-2000 from a median survival of 27 months (range 21-33 months) only five years earlier, 1990-1994. Five years after their diagnosis with metastatic disease, 40 percent of these patients were still alive, as compared with 29 percent during 1990-1994. At the initiation of their study, during the period 1974-79, only 10 percent of patients were still alive at five years and the median survival was only 15 months (range 11-19 months).

The woman whose breast cancer has metastasized or who has been diagnosed initially at Stage IV must live with the reality that her breast cancer can no longer be cured, and that the disease is very likely to take her life. Consequently, the length of the remaining time she has to live, and the quality of that time, become issues of paramount concern. For her, access to the best care can make a significant difference, both in length of survival and in quality of life. With luck, excellent care, family support, personal motivation, and a skillful oncologist, her disease is likely to respond to a number of lines of treatment that can serve to extend her life-many of which may be quite costly. She may join a clinical trial, or try to get compassionate access to experimental drugs prior to their approval through single-patient INDs or expanded access programs.

Whatever path she chooses, she will be in treatment for the rest of her life, and she will require close follow-up, which will include costly scans and other tests. As her disease progresses, she will need pain-management and control of her other symptoms, and she is likely to undergo several hospitalizations to deal with particular crises in the course of the illness. Eventually, she will need hospice care.

It should be emphasized that costly high-quality healthcare resources that can successfully and optimally prolong life in metastatic breast cancer patients are not available to all patients. When there are inequities in treatment access and quality of care, improvements in breast cancer treatments may increase differences in outcomes for different groups. When it comes to advanced and metastatic breast cancer, death rates may not tell the entire story, which should also include length of survival from diagnosis and quality of life during the time.

Typically, newly approved cancer drugs remain on patent for a number of years, providing exclusive sales rights at non-competitive rates for the pharmaceutical company that developed and is marketing the drug. This ensures that the cost of receiving the latest treatments will remain high, not only for patients, but for health management companies, insurers, the Medicare system, and especially for the ever-enlarging percentage of the population who remain uninsured and under-insured, for whom the innovations capable of prolonging life may be completely out of reach. While most pharmaceutical companies do have programs that partially or completely fund some treatment for people who can't afford it, the potential need for assistance greatly outstrips these resources. Thus, improvements in care during the last decade both in the adjuvant care of high-risk patients and in metastatic treatment to prolong life and improve quality of life for Stage IV and recurrent patients may not reach all those in need.