ATLANTAAll breast cancer patients under age 35 should be
offered adjuvant chemotherapy even if they have low-risk disease,
Mads Melbye, MD, PhD, said at the Era of Hope: U.S. Department of
Defense Breast Cancer Research Program Meeting.
He presented results of a 10,000-patient retrospective study from
Denmark to support the recommendation.
In this study, without follow-up chemotherapy, women under age 35
with low-risk disease were more than twice as likely to die of their
disease as comparable patients aged 45 to 49 at diagnosis. In
contrast, among those receiving adjuvant chemotherapy, young women
did not die more often than middle-aged women.
Dr. Melbye is professor of epidemiology research, Statens Serum
Institut, Copenhagen. He and his colleagues reviewed data from a
population-based registry, maintained by the Danish Breast Cancer
Cooperative Group since 1977, of 10,356 women who were less than 50
years of age when diagnosed with breast cancer.
The largest group was 4,402 women in the 45 to 49 age range, which
the researchers set as the reference. The main outcome measure was
the risk of dying within the first 10 years after diagnosis, adjusted
for known prognostic factors and expected mortality.
Our detailed information on tumor characteristics at diagnosis
enabled us to adjust for the effect of factors such as tumor size,
nodal status, and histologic grade, and therefore judge more clearly
the independent effect of age, Dr. Melbye commented.
Overall, the researchers found that the younger women had an elevated
relative risk of dying; those under age 35 had the worst prognosis
(relative risk, 1.46).
The researchers then examined risk of dying for different age groups
among the 4,329 low-risk patients, none of whom received adjuvant
chemotherapy, and among the 2,824 high-risk patients, all of whom
received adjuvant chemotherapy.
women with low-risk disease who received no adjuvant cytotoxic
treatment, the risk of dying increased significantly with decreasing
age at diagnosis (see Table). The researchers did not see a similar
trend for younger women in the high-risk group who did receive chemotherapy.
Following the conference, Dr. Melbye told ONI, I want to
stress that this study was not planned as an intervention trial where
one arm got chemo and the other did not. The data derive from a very
large, population-based registry on all women in Denmark treated for
breast cancer. Nevertheless, the findings are so robust that we
believe most young women might benefit from cytotoxic treatment.
He then added, There is always a price to paythe risk
that we will overtreat some women. At the moment, we can only point
out to women the poor survival among low-risk patients who are not
More precise knowledge would require a clinical trial, but that might
be difficult to do, Dr. Melbye said, in light of the findings from
this retrospective study and the fact that breast cancer is rare
among younger women, making it difficult to enroll sufficient
Until this study, higher mortality rates in younger women were
thought to be due to their having more aggressive tumors. Previous
research had shown that younger breast cancer patients were more
likely to have affected lymph nodes, be negative for estrogen
receptors, and have tumors that are large with a high grade of
anaplasia. Yet Dr. Melbyes group found that use of adjuvant
chemotherapy was more important than age in determining outcomes.
No matter how we examine the data, the conclusions are the
same, he said. The researchers had the same results when they
looked exclusively at women with node-negative disease and again when
they looked only at women with small tumors (2 cm or less) or large
tumors (greater than 2 cm) at the time of diagnosis.
Although the study included 867 women under age 35 at diagnosis, the
sample was too small to compare outcomes with chemotherapy vs without
chemotherapy in that age group.
A direct comparison of those below 35 years with and without
chemotherapy was difficult to perform simply because the
recommendations for low-risk disease patients until recently had been
not to give systemic chemotherapy, Dr. Melbye said. Thus, his
group looked at the age effect within the group of women who did not
receive chemotherapy and the group who did.
We found a clear indication that age was unimportant in the
chemotherapy group whereas among those low-risk women who did not
receive chemotherapy, the young women did significantly poorer than
comparable middle-aged women.
The full report of the study has been published in the British
Medical Journal (320:474-479, 2000).