Recent Advances in the Treatment of Refractory Advanced Breast Cancer

The incidence of breast cancer has risen steadily over the pastseveral decades. Breast cancer is second only to lung cancer asa cause of cancer deaths among women; 46,000 women died of breastcancer in the United States alone in 1995. Despite efforts toimprove the survival of women with metastatic breast cancer withcurrently 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 theTreatment of Refractory Advanced Breast Cancer" was convenedto attempt to make sense of the existing data on breast cancerrefractory to hormonal therapy and to examine current and futuretreatment approaches for this challenging and complex disease.

Our first two contributors, Dr. Charles L. Vogel and Dr. EricP. Winer, take a personal approach to this issue. Because thereis considerable disparity in the definition of "refractoryadvanced breast cancer" in the medical literature, both authorsbegin with their definition of this term. Furthermore, they examineto what extent clinically meaningful responses can be achievednot only with first-line and second-line chemotherapy but alsowith third-line or higher chemotherapy, especially among sucha heterogeneous population.

The consideration of a patient's wishes is important when discussingtreatment options. In a prospective study, Slevin et al1 foundthat patients with newly diagnosed solid tumors referred for considerationof treatment with cytotoxic therapy were much more likely to optfor radical treatment with a minimal chance of benefit than werepersons who did not have cancer, including medical and nursingprofessionals.

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

This study has implications for the treatment of metastatic breastcancer in today's marketplace, because inevitably individualswho control access to therapy by other than monetary means arealmost universally not the people with cancer. It is difficultto assess the impact of therapy on both survival and quality oflife; however, of these two factors, evaluating the impact oftherapy on quality of life is the most arduous task because thereare few objective measurements. There is no generally acceptedstandard for assessing quality of life, and only recently haveformal studies of this endpoint begun to appear in the medicalliterature. In addition to the differences in valuation of therapydescribed by Slevin et al,1 these problems have led to the denialof coverage for treatments that the majority of patients withcancer consider to be worthwhile.

Such issues are also important to consider in the developmentof new cytotoxic agents, as discussed by Dr. Gabriel N. Hortobagyi.Between 1974 and 1993, no drugs for the treatment of breast cancerwere approved by the Food and Drug Administration. Over the past2 years, two drugs have been approved: paclitaxel (Taxol) anddocetaxel (Taxotere). However, other drugs appear to have as muchvalue in palliating symptoms with less toxicity than these drugs,notably, mitoxantrone (Novantrone) and vinorelbine (Navelbine).In addition, new agents have entered clinical evaluation overthe past several years, and they show promise in providing additionalalternatives that may be either less toxic or more effective thancombinations used in the past.

Dr. Hortobagyi and his colleague Dr. Nuhad Ibrahim examine howthe combination of new and old agents may hold the best hope forthe 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 beendescribed. However, information regarding long-term toxicity doesnot yet exist.

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

References:

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.