Risk
of Second Malignancies After Adjuvant Radiotherapy for Breast
Cancer: A Large-Scale, Single-Institution Review
Kirova.
IJROBP 2007;68:359
Purpose: The
aim of this study was to estimate the risk of second
malignancies (SM) after radiation therapy (RT) for breast
cancer (BC) in a large, institutional, homogeneous cohort of
patients.
Methods and
Materials: We retrospectively studied 16,705 patients
with nonmetastatic BC treated at the Institut Curie in Paris
between 1981 and 1997.
Adjuvant RT was
given to 13,472 of these patients, and no RT was given to
3,233. The SM included all first nonBCs occurring
during follow-up. Cumulative risks for each group were
calculated using Kaplan-Meier estimates, censoring for
contralateral cancer or death.
Results:
Median patient age at diagnosis of BC was 55 years for the
whole population, and 53 and 60 years for patients who had
and had not undergone irradiation, respectively. At the
10.5-year median follow-up, 709 patients were diagnosed with
SM (113 in the non-RT and 596 in the RT group). There was a
significant increase
in the rate of sarcomas and lung cancers in the RT group
compared with non-RT group (p 0.02). Treatment with
RT was not found to increase the risk of other types of
cancers such as thyroid cancer, malignant melanoma,
gastrointestinal or genitourinary, and hematologic SM.
Conclusions:
This study suggests that adjuvant RT increased the rate of
sarcomas and lung cancers, whereas it did not increase the
rate of other malignancies.
Adjuvant RT
plays a significant role in preventing local failure in women
treated for early-stage breast cancer (BC). Many randomized studies
over the past 30 years have studied the importance of RT in local
control. A recently updated
meta-analysis showed that the RT regimens produced moderate but
definite reductions not only in 15-year BC mortality but also in
15-year overall mortality.
Sarcomas are a rare but
recognized complication of radiation therapy (RT) for BC, also some
other cancers such as lung carcinomas, mostly in smokers. Recently
increased risk of esophageal cancer after adjuvant RT for primary BC
has been reported. The role of adjuvant RT for BC in causing
secondary cancers is debatable.
Discussion
This
large-scale, single-institution, retrospective study of 16,705
patients treated for nonmetastatic BC suggests that RT did not
increase the incidence of second primary cancers other than sarcomas
and lung cancer. To our knowledge, this is the largest series from a
single institution.
Our results
could be discussed in the context of the existing literature,
especially recently published results of meta-analyses (Table 3).
The weakness of some large epidemiologic studies, despite very large
populations studied and long follow-up periods, is the lack of
individual information concerning the patients’ treatment,
especially information concerning irradiation fields. Other
single-institution series are limited by small numbers of patients,
but they have confirmed the relationship between RT and arising of
sarcomas
This study
showed the increased risk of sarcomas and lung cancers. The risk
of radiation-induced sarcomas is well known, and our experience
is previously described. It is already shown that approximately
9 cases of radiation-induced lung cancer per year could be
expected to occur among 10,000 women who received an average
lung dose of 10 Gy and survived for at least 10 years. Another
problem, as confirmed by present study, is that lung cancer is
greater among cigarette smokers and it is extremely difficult to
analyze the risk in this patient population. Our study confirms
also the findings of Galper , who reported increased risk of
lung cancers and sarcomas. In some cases, lung cancers such as
SM may be sporadic and/or related to environmental factors, and
in others it may be related to BC treatment such as RT. Another
diagnostic problem is to distinguish a new lung primary from a
lung metastasis from BC, especially in cases of adenocarcinoma.
As previously reported, some of our patients with lung cancer
had been treated in another hospital. The histologic
confirmation of their lung cancer, all simulation films and
radiologic charters of the BC treatment were available but in
more than 60% of the cases the precise localization of new lung
primary was not found. We were thus unable to determine the
precise relationship between the lung SM and irradiation fields
and doses. At the other hand, Obedian did not find an increased
risk in lung cancers among patients who have undergone
irradiation compared with matched control subjects treated with
mastectomy without RT. Based on analysis of the study findings
and previously published data
it is concluded
that patients who undergo RT and who are smokers present with an
increased risk of lung cancer. This population of
patients may need to undergo follow-up using computed tomography
as screening for early detection of lung cancer.
Some
recently published studies showed increased incidence of
esophageal cancers
after RT. The recently published study in the SEER
series showed that postmastectomy RT moderately increases the
risk of squamous cell esophageal carcinoma starting 5 years
after exposure and persisting after 10 years, with no increase
in the risk of adenocarcinoma. Other investigators did not
find any difference in the incidence of GI malignancies in
patients who had and had not undergone RT, as in the present
series.
In this
study there was no
significant difference between the populations of patients who
had and had not undergone RT for contralateral BC (Table 2).
This finding shows that, in our population, there were no
radiation-induced contralateral cancers. The use of adequate,
individually adapted technique is an important part of
breast-conserving treatment.
As
recommended, longer and careful follow-up of these patients is
required to confirm the validity and stability of these results.
Despite the importance of studied population and the follow-up
period (nearly 11 years), this may still not have been long
enough to detect a difference in the incidence of SM between the
patients who had and had not undergone RT, because the long
latency of radiation-induced tumors
Conclusion
In
conclusion, second malignancies occur in a minority of patients
undergoing RT for BC. Adjuvant RT increased the rate of sarcomas
and lung cancers, whereas it did not increase the rate of other
malignancies. Long-term follow-up is needed for this patient
population to exclude other late complications.
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