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ABSTRACT: A Systematic Overview of Chemotherapy Effects in Breast
Cancer
[08/13/2001; Acta Oncologica]
A systematic review of chemotherapy trials in several
tumour types was performed by The Swedish Council of Technology
Assessment in Health Care (SBU).
The procedures for the evaluation
of the scientific literature are described separately (Acta Oncol
2001; 40: 155-65). This synthesis of the literature on chemotherapy
for breast cancer is based on 233 randomised studies, 9 meta-analysis
of randomised studies, a population-based cohort study and 18
overviews/retrospective analyses including a total of 155 243
patients. The conclusions reached can be summarised into the
following points:
Adjuvant treatment:
- There is solid scientific support from randomised studies
that adjuvant polychemotherapy at 10 years will result in
an absolute mortality reduction for patients younger than
50 years by 12% for node positive (34% relative mortality
reduction corresponding to an estimated median survival
prolongation of several years) and 6% for node negative
patients.
For women aged 50 to 69 years, the corresponding
figures for node positive and node negative patients are
6% and 2%, respectively (approximately 11% relative mortality
reduction).
- Anthracycline-containing combinations result in an absolute
survival benefit at five years of 3% compared with
non-anthracycline based polychemotherapy.
- There are indications that the taxane paclitaxel may further
improve the survival compared with anthracyclines. However,
the limited data preclude conclusions for the routine care.
- The addition of tamoxifen to chemotherapy further enhances
the survival benefit for receptor positive subgroups.
- The roles of more dose-intensive regimens, including high-dose
therapy with stem cell support, are presently studied in
randomised investigations. The data presented so far are
conflicting but they do not in general support high-dose
therapy.
- Quality of life, based on analyses of randomised studies,
demonstrate that adjuvant polychemotherapy has an initial
detrimental effect, but long-term follow-up of treated patients
demonstrates no impairment of quality of life compared with
untreated patients.
- Polychemotherapy in standard doses should be offered to
premenopausal node positive patients, and the corresponding
postmenopausal group with a receptor-negative breast cancer
and to node negative patients with high risk factors.
Polychemotherapy should be combined with tamoxifen to all
patients with receptor-positive tumours. Due to a need of
more knowledge in this field, patients should be included
in investigational protocols.
Locally advanced breast cancer:
- Based on current knowledge, treatment of patients with
locally advanced breast cancer should include
neoadjuvant/preoperative polychemotherapy since there
is evidence from controlled studies that such therapy will
statistically significantly increase the number of patients
who can be offered breast-conserving surgery.
Indirect
comparisons also demonstrate survival improvements, but
the scientific support is equivocal.
Metastatic breast cancer:
- The median survival for patients with metastatic disease
treated with conventional chemotherapy doses and regimens
is 12 to 24 months.
- Retrospective cohort studies indicate that the use of
non-anthracycline containing chemotherapy compared with
no chemotherapy might add a survival gain of six to
nine months.
However, this estimation is based on equivocal
data.
- Based on overview data, polychemotherapy results in a
statistically significant survival gain compared with
single-agent therapy.
- Based on repeated randomised studies, the addition of anthracyclines
increases the response rate and statistically significantly
improves the survival compared with non-anthracycline containing
chemotherapy, except for CMF combined with prednisone/prednisolone,
which will statistically significantly improve the survival
compared with some anthracycline combinations.
- Second line therapy using vinorelbine or docetaxel is statistically
significantly better than other regimens with a time to
progression and survival benefit in the order of one to
three months based on few randomised studies. The role, if any,
of third line therapy is yet to be demonstrated.
- In the metastatic setting, conventional chemotherapy improves
the quality of life.
- In standard care, first line therapy should contain an
anthracycline and second line therapy using vinorelbine or
docetaxel could be offered to selected patients failing first
line therapy.
- Based on numerous randomised studies, breast cancer demonstrates
a positive dose-response relationship both in the adjuvant
situation and for metastatic disease. However, in the
conventional dose-range there seems to be a plateau in the
dose-response curve, with no further survival gains for
higher doses.
- High-dose therapy with bone marrow support might result in
further increases in antitumour effects with the potential
of increasing survival, but additional phase III studies
are required before this can be recommended for routine care.
- The growth factors G-CSF and GM-CSF reduce chemotherapy-induced
hematological toxicity. So far their use has given no proven
effect on survival.
- There is no support that unspecific immunomodulation improves
the outcome in breast cancer. A clinical benefit from
monoclonal HER-2 antibodies is suggested but needs
further confirmation.
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