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,
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
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.