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Breast Cancer
Advances in Chemotherapy for Metastatic Breast Cancer
a report by
Erica A Mayer, MD, MPH
Dana-Farber Cancer Institute, and Brigham and Women’s Hospital, Harvard Medical School
Despite many advances over the past few years in the adjuvant treatment of studies have demonstrated that although continuous ‘maintenance’ therapy
breast cancer, a significant number of patients develop metastatic disease. can prolong time to progressive disease, as ‘observation’ patients can
Furthermore, a small yet consistent percentage of women are diagnosed reinstigate therapy at time of progression no difference in survival emerges
with de novo metastatic disease. Once the disease has spread outside the between the two methods of administration.
8,9
In practice, chemotherapy
locoregional area of the breast and draining lymph nodes, it is considered tends to be given in a continuous fashion as long as there is demonstrated
incurable, historically with a median survival of two to three years. More evidence of response or stable disease and the patient does not experience
recent analyses of outcomes with modern treatment regimens suggest an significant toxicity. Treatment ‘holidays’ can be instituted in the setting of
improvement in median survival, with patients occasionally living for a prolonged stable disease, with resumption of prior therapy if necessary. In
prolonged period of time with metastatic disease.
1,2
Systemic therapy is the cases of definitive radiological or clinical progression, indicating resistance to
primary modality of treatment, given with the dual goals of prolongation of the ongoing therapy, the regimen is changed to a different agent.
survival and palliation of symptomatology. Selection of agents, timing
of initiation and discontinuation, and incorporation of novel therapies is both Multiple chemotherapeutic agents have demonstrated activity in the
a science and an art. For many women, sequential use of appropriate therapy treatment of advanced breast cancer. Generally, anthracyclines and taxanes
can translate into years of prolonged survival with preserved quality of life. are considered the most active agents. However, as many patients have
received these as part of adjuvant treatment, alternative agents are often
The decision of when to initiate chemotherapy for breast cancer depends on selected in the metastatic setting, with no consensus opinion on a
the characteristics of both the patient and the tumor. In the absence of preferable order of therapy.
10
Considerable practice variation exists in the
significant symptomatology or visceral organ compromise, individuals with selection and timing of agents, and decisions typically reflect previous
hormone-responsive disease are preferentially started on an appropriate treatment history, tumor characteristics and burden, comorbid toxicities,
endocrine therapy. Suitable agents include aromatase inhibitors, tamoxifen, and patient preference. Does this variation influence patient outcome? The
fulvestrant, or ovarian ablation (if pre-menopausal). Typically, Cancer and Leukemia Group B (CALGB) compared first-line therapy with
commencement of chemotherapeutic treatment is reserved for hormone conventional anthracycline-based chemotherapy with treatment with an
receptor-negative disease, disease refractory to further endocrine experimental agent as part of a clinical trial.
11
No difference in overall
maneuvers, rapid progression, or visceral organ crisis. Concurrent use of survival was found between the two arms, despite higher responses in the
endocrine and chemotherapy treatment is usually avoided due to concerns conventional therapy arm, suggesting that diversity in practice does not
regarding potential negative interactions. Historical trials comparing result in differential outcomes.
chemohormonal therapy with chemotherapy alone suggest that the
addition of an endocrine agent does not compromise response and The specific data supporting the use of contemporary chemotherapy agents,
prolongs time to treatment failure, although it does not translate into an including adriamycin, paclitaxel, docetaxel, capecitabine, vinorelbine,
overall survival benefit.
3,4
Usually, chemotherapy is administered in cycles gemcitabine, liposomal doxorubicin, and epirubicin, have been reviewed
consisting of three- to four-week units, with interval clinical and radiological extensively.
12
Although the treatment options have remained constant over the
restaging to evaluate for response. Response to therapy depends on
multiple factors, most importantly prior exposure to chemotherapeutic
agents. Responses are significantly higher in chemotherapy-naïve patients
Erica A Mayer, MD, MPH, is a Staff Physician at the Dana-Farber
Cancer Institute in Boston and an Instructor in Medicine at
compared with those who have received adjuvant therapy, and in the first-
Harvard Medical School. Her research explores the use of novel
line metastatic setting compared with successive lines of therapy.
5,6
agents for the treatment of breast cancer, including evaluation
Although an objective response to therapy is a goal of chemotherapeutic
of anti-angiogenic strategies for all stages of breast cancer. She
is also involved in ongoing nationwide efforts to find better
treatment, achieving stable disease may also be a desirable objective, as a
treatments for the aggressive triple-negative breast cancer
significant proportion of patients who achieve stable disease experience
subset. In addition to her research work, she maintains a busy
improvements in cancer-related symptoms and quality of life.
7
clinical practice at Dana-Farber. Dr Mayer is a graduate of
Harvard Medical School. She completed her internal medicine residency at Brigham and Women’s
Hospital and a fellowship in medical oncology at the Dana-Farber Cancer Institute in Boston,
Variable methods of administration of chemotherapy for metastatic breast
while also obtaining a Masters in Public Health from the Harvard School of Public Health.
cancer exist, and multiple clinical trials have evaluated whether
E:
Erica_Mayer@dfci.harvard.edu
chemotherapy should be given in a continuous or interrupted fashion. These
© TOUCH BRIEFINGS 2008
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