2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

A Dickens Tale of the Treatment of Advanced
Breast Cancer: The Past, the Present, and
the Future
By George W. Sledge Jr., MD, Fatima Cardoso, MD, Eric P. Winer, MD,
and Martine J. Piccart, MD
Overview: Metastatic breast cancer (MBC), a usually incurable
disease, continues to vex physicians and patients. Recent
decades have seen great improvements in the treatment of
MBC, based on the availability of novel targeted therapeutics
and more standard chemotherapeutic agents. This article
POTENTIAL GOALS of care in MBC include cure, prolongation
of survival, palliation of symptoms and maintenance
of quality of life, the development of new treatment
options, and what might be termed “a good death” for
patients with advanced disease.
Cure
Metastatic breast cancer is usually incurable. Nevertheless,
there are patients who are long-term survivors of the
disease (whether the word “cure” should be applied to such
patients is contentious). Though the overall percentage of
patients is small (1% to 2% of patients in the largest
reported series), their existence is inarguable and suggests
that long-term survival represents a possible goal, if a rare
one. 1
Prolongation of Survival
If cure is rare, prolongation of survival nevertheless represents
a reasonable goal. How much does therapy improve
survival in metastatic breast cancer? We lack trials comparing
active therapy with best supportive care. Studies suggesting
an improvement over time in median survival 2
imply that this improvement is related to therapy, but are
potentially flawed because of earlier detection of metastatic
disease. A recent study by the Eastern Cooperative Oncology
Group has suggested that, adjusted for disease relapse-free
interval, overall survival (OS) of patients with metastatic
disease has not improved. 3
The best evidence for improvements in survival comes
from studies comparing active therapies. These include
comparisons of anthracycline- with nonanthracycline-based
therapies, of chemotherapy with chemotherapy plus HER2targeted
therapy, of aromatase inhibitor therapy with tamoxifen
in estrogen receptor-positive disease, and of
eribulin with doctor’s best choice. 4-7 In each of these cases,
the improvement associated with the new intervention is
measurable in months. The cumulative effect of such improvements
is hard to quantify.
As current patients are more heavily pretreated (because
of increasingly intensive adjuvant therapies) than their
predecessors, it may become increasingly difficult to demonstrate
improvements in OS. The availability of multiple
lines of systemic therapy in the metastatic setting may also
dilute or hide the benefit of individual new agents, whether
in the front-line or refractory disease settings. 8
28
describes the goals of therapy for MBC, the progress made
against MBC in recent decades, the current standard of care,
and the ongoing efforts of basic and translational researchers
to transfer the fruits of modern scientific discovery to patients
in the clinic.
Palliation of Symptoms and Maintenance of
Quality of Life
Metastatic breast cancer impairs quality of life through its
symptom-producing effects on organ-specific function (e.g.,
bone metastasis-related fractures and pain) and general
effects on quality of life (both physical and psychologic). An
important part of the physician’s role is to maintain patient
quality of life and palliate cancer-related symptoms.
The tools available for this task have expanded in recent
decades. These include appropriate pain control, treatment
of isolated metastases (e.g., brain metastases and epidural
cord compression), antiemetic therapy, bone maintenance
therapy (with bisphosphonates and denosumab), and psychosocial
and dietary interventions. Appropriate pain control
in particular is critical, and prompt referral to pain
specialists and palliative care experts is valuable in complex
cases.
Systemic therapies obviously play a role in maintenance of
quality of life and palliation of symptoms. Measuring the
effects of systemic therapy on health-related quality of life in
the metastatic setting has been difficult because of the
general lack of placebo-controlled trials, the inherent difficulty
of measuring health-related quality of life over time,
and the competing toxicities of systemic therapy.
Psychosocial support, often for the patient and the family,
is equally important, and symptoms of insomnia, anxiety,
and depression often require treatment. In the optimal
situation, palliative and psychosocial care should be seamlessly
integrated into the medical care provided by the
primary oncologist after discussion with a multidisciplinary
team.
Developing New Agents
The metastatic setting has played an important role in the
cure of micrometastatic breast cancer through the development
of novel agents applicable to early disease. Physicians,
patients, and society in general owe much to the altruism of
patients with MBC. All patients with MBC should be offered
clinical trials of novel agents as an appropriate treatment
From the Indiana University Simon Cancer Center, Indianapolis, IN; Breast Unit,
Champalimaud Cancer Center, Lisbon, Portugal; Dana-Farber Cancer Institute, Boston,
MA; Institut Jules Bordet, Université Libre de Bruxelles, Belgium.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to George Sledge, Jr., MD, Indiana Cancer Pavilion, 535
Barnhill Dr., RT-473, Indianapolis, IN 46202; email: gsledge@iupui.edu.
© 2012 by American Society of Clinical Oncology.
1092-9118/10/1-10