ARTICLE
Auteur(s) : B
Séradour1, H Allemand2, A
Weill2, P Ricordeau2
1Arcades (Association pour la recherche et le
dépistage des cancers du sein, du col de l’utérus et des cancers
colorectaux), parc Mure, bâtiment A, 16, boulevard des Aciéries,
13395 Marseille cedex 10, France
2CNAMTS (Caisse nationale d’assurance maladie des
travailleurs salariés), 50, avenue du Professeur-André-Lemierre,
75983 Paris cedex 20, France
Introduction
Breast cancer incidence rate has continuously risen in France,
during the period 1978-2000, by 2.4% per year [1]. The greatest
increase was observed in women aged 50-74, with an increase of
almost 3% per year between 1983 and 2002 [2]. Recently, we reported
a first decline of breast cancer incidence in France, in 2005 and
2006, among women aged 50 years or above [3], like in the
United States in 2003 [4], in Australia [5] and in Europe [6].
Possible explanations for these patterns include change in
lifestyles, the effects of widespread screening and decreased use
of hormone replacement therapy (HRT). The potential contribution of
mammography screening and HRT use to those breast cancer incidence
trends is unclear, because of marked changes concerning these two
factors at the same period in France.
The development of screening was gradual between 1980 and 2004.
In 2004, the National Programme achieved complete geographic
coverage and targeted eight millions women aged 50-74. This program
invites all women for a free mammography every two years with
double reading. Between 2000 and 2006, the use of screening
mammography has continuously increased, mixing opportunistic and
organized screening. Before 2002, the prevalence of HRT use was
high. After the publication of the Women's Health Initiative (WHI)
study [7], use of HRT substantially dropped in France. HRT has been
implicated as a risk factor for breast cancer, and the recent
decline in breast cancer incidence in the US was largely attributed
to the decline in HRT use [4, 8-10]. We have the opportunity to
examine by 5-year age groups the incidence trends in France between
2000 and 2006 and the potential association between mammography
screening, HRT use and recent changes in breast cancer
incidence.
Methods
Our study population comprised female affiliates of the general
scheme of the French National Health fund between January 1st 2000
to December 31 2006. The fund includes 86% of the French
population. The data cover the entire French territory
(28 million women). Breast cancer incidence rates were
calculated from the new cases of breast cancer among affiliates of
the general scheme of the French National Health Fund who received
first time approval for their long-term disorder. In France, their
referring physician notified patients with a long-term disease,
including breast cancer, to the National Health Insurance. The
definition of long-term disorder is not only of a medical nature,
but also administrative: those patients are free of co-payments.
Annual breast cancer incidence rates were calculated every six
months, in January and June (rolling year-to-date values) over the
2000-2006 period for each age group. Population data were retrieved
from the National Institute for Statistics and Economics Studies
(Insee) datasets. Annual breast cancer incidence rates were age
standardized for all age groups with the 2000 French standard
population. The data included invasive and in situ breast cancer
cases (ductal carcinoma in situ), but the pathology reports are not
recorded, and information on receptor status is not available.
Trends in breast cancer incidence were analysed for women aged
30 to 49, 50 to 69, 70 to74 and over 75 years old. For the
group aged 50 to 69, we further investigated incidence rates by
5-year subgroups (50-54; 55-59; 60-64; 65-69). For each 5-year age
group, we compared trends in incidence rates between 2003 and 2006.
For the broader group aged 50 to 69 years, we calculated
relative age-adjusted incidence rates using the Mantel-Haenszel
method.
Mammography data were extracted from the reimbursements
databanks of the National Health fund for all mammograms performed
between 2000 and 2006. The National Institute of Public Health
(INVS) collected data of the National Screening Programme. An
annual report has been published for evaluation of the screening
programme since 1998.
HRT data were extracted from the reimbursements databanks of the
National Health fund. Prescriptions defined as HRT were oral or
transdermal, estrogen only HRT or combined estrogen-progestagen HRT
preparations. Our data based on dispensation do not distinguish
between data on estrogen-only HRT and data on combined HRT
preparations. We defined users of HRT as anyone who has received at
least two HRT prescriptions during the year. HRT data were
collected from 2000 to 2007.
Results
In our data, incidence rates increased gradually from mid-1999 to
2006 for women less than 50 years old. Starting in 2004,
breast cancer incidence decreased in all age groups among women
aged 50 years or above, although the magnitude and timing of
decrease varied by age (figure 1). Among women
aged 50-69, the decrease began in mid-2003, and between 2003 and
2006 the percentage decrease was 6.3 (95% CI: 4.6 to 7.9%). For
women of 70-74 years old, the incidence increased by 25% (95%
CI: 20.2 to 30.0%) from 2002 to 2004, after the implementation in
2002 of organized screening in this age group, and decreased 8.4%
(95% CI: 4.9 to 11.9%) from 2004 to 2006. In the group of women of
75 years old and above, the incidence decrease was 3.7% (95%
CI: 0.6 to 6.7%) between mid-2004 and 2006.
Figure 2
shows trends in age-specific breast cancer incidence rates in four
different age groups among women of 50 to 69 years old. The
highest incidence rates were observed in the 60-64 age group
between 2000 and 2006. The largest percentage decreases from 2003
to 2006 occurred in women aged 55-59 years old (12.9%; [95%
CI: 10.0 to 15.8%]) and 60-64 years of age (7.7%; [95% CI: 4.3
to 10.9%]). For women of 65-69 and 50-54 years old, the
decreases were 2.1% (95% CI: –1.6 to 5.8%) and 0.7% (95% CI: –2.8
to 4.1%), respectively.
Data from organized screening showed a rapid increase between
2000 and 2006: 478,450 mammograms in 2000 and 2,080,000 in
2006. Attendance rates increased from 40% in 2004 to 48% in 2006.
The use of mammography including opportunistic screening and
diagnostic mammography has continuously increased between 2000 and
2006 and all mammograms have increased from 1,600,000 to 3,470,000
for women aged 50-74. 37.3% of this population had undergone a
mammography in the last two years in 2001 versus 62.8% in 2006.
This upward trend concerned all age groups over 50.
Data from HRT use of the National Health Fund showed a decline
of 62% from 2001 to 2006 for women aged 50 to 64 years old,
with a sharp decrease between 2002 and 2004 in all 5-year age
groups (figure
3). HRT use was very common in France for women aged
50-64 years old before 2002 but after 2005, less than 15% of
women were receiving this type of treatment. The largest decline
occurred in women aged 55 to 59 years old: 38.2% were users in
2001, and only 14.5% in 2006.
Discussion
In France, data from cancer registries show that invasive breast
cancer incidence has been increasing continuously by an average of
about 2.4% per year between 1980 and 2003. Registries are the
standard in recording cancer cases, but those registries cover only
about 16% of the French population. In this report, we provide
national data of the medico-administrative database for long-term
disorders between 2000 and 2006. In contrast, our results show a
decline in the incidence of breast cancer among women aged over or
equal 50 years between 2003 and 2006. Incidence rates include
in situ and invasive breast cancer cases. Those data are not
collected for epidemiological purposes but allow to quickly
identifying changes of trends in cancer incidence at the national
level. All the women treated for breast cancer are registered, and
the system was unchanged between 2000 and 2006.
The magnitude and timing of decrease varied by age, and the
highest decline was observed among the women aged 55-59 and
60-64 years old (12.9 and 7.7%, respectively). The decline
began mid-2003 and was regular until 2006. In the youngest group
(50-54), the incidence rates were almost stable (–0.3%) between
2003 and 2006, and we observed only a slight decrease among the
women aged 65-69 (2.1%). Specific data on in situ carcinoma are not
available in the database. Among the cancers detected by organized
screening, the percentage of ductal carcinoma in situ was stable
between 13 and 15% from 2000 to 2005 [11]. A decrease of in
situ breast carcinoma has not been documented in France during this
period. Somewhat unexpected is the decrease in incidence in 2005
and 2006 after full national coverage of the screening program in
2004. This context is different from the US where the percentage of
women that have undergone a mammography in the last two years has
stabilized since 1999 [12, 13].
Given these findings, changes in screening are not a major
factor contributing to the decline of breast cancer incidence in
France. As in other countries (US, Australia, Germany, New Zealand)
[4-6, 14], the decrease in breast cancer incidence after 2004 seems
to be temporally related to the substantial drop in the use of HRT
ensuing the first report of WHI in 2002. Use of HRT was very common
in France after 1990 and culminated in 2001. The number of HRT
prescriptions dropped by 62% between 2002 and 2006 with a sharp
decline in 2004 and 2005. During the same period, a significant
fall in breast cancer incidence occurred among women over
50 years. Results from WHI study and from the Million Women
Study (MWS) [15] showed a significant increase of breast cancer
with increasing total duration of use in current users of HRT. The
observed decrease in HRT use in France was largest in women 55 to
64 years old because in that population HRT use was
widespread, and the duration of use was longer. In the
50-54 year age group, incidence rates remained quite stable
over this period, and the total duration of use of HRT was lower
than five years for the majority of women. In the French E3N cohort
study [16], the mean age at treatment was 52.4 years, and 70%
of women had used HRT for a mean duration of seven years. Between
50 and 64 years, effects of screening on incidence have been
largely obscured by changes in HRT use. The role of HRT may be seen
as a promoter fuelling the growth of subclinical hormone-sensitive
tumors [17, 18] and increasing breast cancer incidence. On the
other hand, HRT is also associated with an increase in mammographic
breast density and a decrease in sensitivity and specificity of
mammography screening [19, 20]. Cessation of HRT could result in a
short-term increase in breast cancer incidence, adding particular
complexity to analyze the recent changes observed in France. Before
2002, breast cancer incidence has risen with an increase of almost
3% per year [2]. It is impossible to sort out the effects of
changes in screening and HRT use. These effects are superimposed
upon birth cohort patterns due to generational changes in
reproductive behavior. We observed in France the highest incidence
rates among women aged 60-64 years as has been reported in
Geneva [21]. France and Switzerland both have high-levels of
screening and HRT use at the same period. HRT and screening could
explain this shift in age-incidence. After 2002, the rapid fall in
HRT coexisted with the development of organized screening. Between
2003 and 2006, HRT prescriptions and breast cancer incidence rates
followed parallel tracks of decline for women 55-59 and
60-64 years old. The decline in incidence in France was less
dramatic than in the US because of the progressive implementation
of screening.
Beyond the age of 65, the number of users decreases and the
impact of decline in HRT use on breast cancer incidence is lower.
In the 70 to 74 year old age group, changes in screening
patterns are sufficient to explain changes in breast cancer
incidence after 2002.
In a national survey in 2000, 83% of the users received combined
estrogen-progestagen preparations and 17% estrogen only HRT [22].
In France, the range of HRT preparations differs from what is found
in the United States and conjugated estrogens and
medroxyprogesterone acetate are not prescribed. Breast cancer risk
varies according to the types of progestins combined with estradiol
[16]. In the French E3N cohort study, the risk was significantly
lower with progesterone or dydrogesterone than with other
progestagens [23]. However, between 1990 and 2002, less than 50% of
women used estrogen-progesterone or estrogen-dydrogesterone
combinations. The other therapies combined estradiol with different
synthetic progestins. We have no information available on other
drugs that can influence breast cancer incidence, such as tibolone,
tamoxifen or raloxifene. A small minority of postmenopausal
women used these drugs, but they were not reimbursed by Social
Security for this clinical indication. Generally in Europe, the
pattern of HRT use is different from that in the US. Moreover,
there are large disparities in prevalence of HRT use in Europe.
France was a high use country like Switzerland, Belgium and
Germany. Our study has limitations like other ecological studies.
Data do not include information regarding individual patients. The
decrease in breast cancer rates for women 55-64 years cannot
be attributed exclusively to the decrease in the use of HRT.
However, rapid changes in reproductive factors, in environmental
exposures or changes in life style factors have not been documented
in France. The only breast cancer risk factor that has changed
substantially between 2002 and 2004 was HRT. Morever, our results
parallel those from the US, Australia, Germany or New Zealand, and
we produce results in a large population set. Continued
surveillance of breast cancer incidence is warranted in France in
the years following large-scale cessation of HRT use. Data from
registries with pathology reports, information on receptor status
of cancers and studies on the role of different progestins and
their duration may allow a better understanding of the complex
variations of breast cancer incidence and the impact of HRT.
Acknowledgements
We thank Anke Neumann for statistical support. We also thank David
Berstein for helpful review of the manuscript.
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