2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

gain, p � 0.0005, 2.2% absolute overall survival gain)
compared with anthracycline-based regimens at 8-years
follow-up. This effect was not statistically significant with
only a 6% relative effect if the anthracycline control arm was
given with a high cumulative anthracycline dose (Fig. 6).
There was no difference in schedule or taxane drug
(paclitaxel or docetaxel).
There was no difference whether endocrine therapy was
given concurrently or in sequence with chemotherapy.
There were no age-related effects by the delivered
chemotherapies, taxane, or anthracycline-based regimens.
Indeed, there was a trend suggesting greater chemotherapy
effect in the age 55 to 69 group than in younger women.
The anthracycline and taxane regimens had similar
antitumoral effects irrespective of patient age, tumor ER
status, whether tamoxifen was given, the combination of ER
by HER2, or the interaction of ER and grade. (Fig. 7).
76
PRITCHARD, BERGH, AND BURSTEIN
Fig. 7. Studies comparing the add-on effect
by taxanes, most AC x 4. Demonstration
of the outcome (breast cancer survival and
overall survival) when the comparator arm
contained higher doses of the nontaxane
drugs, mostly anthracyclines.
Abbreviations: AC, doxorubicin/cyclophosphamide;
RR, recurrence rate; SE, standard
error; (O-E)/V, (observed-expected)/
variance.
Reprinted from The Lancet, 379, Early
Breast Cancer Trialists’ Collaborative Group,
Peto R, Davies C, et al. Comparisons between
different polychemotherapy regimens
for early breast cancer: Meta-analyses
of long-term outcome among 100,000
women in 123 randomized trials, 432–444,
2012, with permission from Elsevier.
Four cycles of doxorubicin and cyclophosphamide produced
a similar result as six courses of standard CMF at 10
years follow-up. Anthracycline regimens with higher doses,
however, reduced the breast cancer mortality by about 4%
at 10 years (a relative improvement of 22%, p � 0.004)
compared with CMF. The overall mortality was improved by
the same extent.
In comparison with no chemotherapy, CMF-like regimens
and anthracycline-based regimens reduced overall
mortality by 6% at 10 years. No subgroup could be readily
identified that did not benefit from chemotherapy. The
CMF-based studies revealed a less distinct message; the
effect seemed less obvious for the elderly (irrespective of
ER status). This could be because of a combination of factors:
lower compliance in those studies run decades ago; no access
to modern antiemetic regimens; a lack of supportive care
measurement; and less patient motivation to accept toxicity