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Recent Advances in the Treatment of Refractory Advanced Breast Cancer

Recent Advances in the Treatment of Refractory Advanced Breast Cancer

The incidence of breast cancer has risen steadily over the past several decades. Breast cancer is second only to lung cancer as a cause of cancer deaths among women; 46,000 women died of breast cancer in the United States alone in 1995. Despite efforts to improve the survival of women with metastatic breast cancer with currently available chemotherapeutic agents, results remain disappointing. The primary use of such agents continues to be for palliation, not cure.

This roundtable discussion on "Recent Advances in the Treatment of Refractory Advanced Breast Cancer" was convened to attempt to make sense of the existing data on breast cancer refractory to hormonal therapy and to examine current and future treatment approaches for this challenging and complex disease.

Our first two contributors, Dr. Charles L. Vogel and Dr. Eric P. Winer, take a personal approach to this issue. Because there is considerable disparity in the definition of "refractory advanced breast cancer" in the medical literature, both authors begin with their definition of this term. Furthermore, they examine to what extent clinically meaningful responses can be achieved not only with first-line and second-line chemotherapy but also with third-line or higher chemotherapy, especially among such a heterogeneous population.

The consideration of a patient's wishes is important when discussing treatment options. In a prospective study, Slevin et al1 found that patients with newly diagnosed solid tumors referred for consideration of treatment with cytotoxic therapy were much more likely to opt for radical treatment with a minimal chance of benefit than were persons who did not have cancer, including medical and nursing professionals.

Patients with cancer indicated that they were willing to experience highly toxic treatment for only a 1% chance of cure; patients who did not have cancer required a 50% chance of cure to justify the same level of toxicity. Patients with cancer were also willing to undergo considerable toxicity for only a 10% chance that the therapy would relieve their symptoms; patients without cancer required a 75% chance of relief to justify the side effects from treatment. Similar but less extreme differences in the chances of benefit were seen when the responses of patients with cancer were compared with those of medical oncologists, radiotherapists, cancer nurses, or general practitioners.

This study has implications for the treatment of metastatic breast cancer in today's marketplace, because inevitably individuals who control access to therapy by other than monetary means are almost universally not the people with cancer. It is difficult to assess the impact of therapy on both survival and quality of life; however, of these two factors, evaluating the impact of therapy on quality of life is the most arduous task because there are few objective measurements. There is no generally accepted standard for assessing quality of life, and only recently have formal studies of this endpoint begun to appear in the medical literature. In addition to the differences in valuation of therapy described by Slevin et al,1 these problems have led to the denial of coverage for treatments that the majority of patients with cancer consider to be worthwhile.

Such issues are also important to consider in the development of new cytotoxic agents, as discussed by Dr. Gabriel N. Hortobagyi. Between 1974 and 1993, no drugs for the treatment of breast cancer were approved by the Food and Drug Administration. Over the past 2 years, two drugs have been approved: paclitaxel (Taxol) and docetaxel (Taxotere). However, other drugs appear to have as much value in palliating symptoms with less toxicity than these drugs, notably, mitoxantrone (Novantrone) and vinorelbine (Navelbine). In addition, new agents have entered clinical evaluation over the past several years, and they show promise in providing additional alternatives that may be either less toxic or more effective than combinations used in the past.

Dr. Hortobagyi and his colleague Dr. Nuhad Ibrahim examine how the combination of new and old agents may hold the best hope for the future management of metastatic breast cancer. In recent years, several combinations with an efficacy similar or, in some cases, superior to that of standard chemotherapeutic regimens have been described. However, information regarding long-term toxicity does not yet exist.

As Dr. Hortobagyi notes, the availability of many new, active, and well-tolerated cytotoxic agents provides a tremendous opportunity to review the effect of chemotherapy on metastatic breast cancer. It is hoped that these articles meet that goal.


1. Slevin ML, Stubbs L, Plant HJ, et al: Attitudes to chemotherapy: Comparing views of patients with cancer with those of doctors, nurses, and general public. BMJ 300(6737):1458-1460, 1990.

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