ARTICLE
Auteur(s) : Mongi
Maalej1, Dalenda Hentati1, Taha
Messai1, Lotfi Kochbati1, Ahmed El
May2, Karima Mrad2, Khaled Beb
Romdhane2, Mansour Ben Abdallah3, Bechir
Zouari3
1Radio-oncology department, Salah Azaiz Institute
2Anatomo-pathology department, Salah Azaiz Institute
3Statistics department, Tunis Faculty of Medicine, Salah
Azaiz Institute, Boulevard 9 avril, Bab Saadoun 1006, Tunis,
Tunisia
Several studies have been carried out in Tunisia especially in
the national institute of cancer of Salah-Azaiz (ISA), about breast
cancer in order to establish its clinical and epidemiological
profile. However, these studies were limited to patients treated in
this institution. Only one large study realised in 1994 included
all the cases of breast cancer diagnosed in Tunisia during this
year - year of the population census [1].
The aim of our study is to take a census of all new cases of
breast cancer diagnosed in Tunisia during the year 2004: from 1st
of January to 31st of December, 10 years after the first study.
The aims of this paper are:
- – to update the incidence of breast cancer in
Tunisia;
- – to precise the epidemiological, clinical and
histological features of this cancer;
- – to compare our results to other previous Tunisian
studies [2-5] and to confront them with data in the literature
[6-8].
Methods
The study was the subject of a thesis of doctoral degree in
medicine. A resident in radiation oncology collected all the data
and was trained by the authors of this article. Statistical
analysis and confrontation of the results were verified by two
teams: one at ISA and the second at the Tunis faculty of medicine.
Our study included all new cases of breast cancer diagnosed from
the 1st of January to the 31st of December 2004. In all cases, a
histopathological or at least a cytological proof was required. All
patients having their biopsy or tumour excision with the first
histopathological or cytological diagnosis out of the two
date-limits were excluded from the study.
Information for this census was collected from:
- – hospital and private pathology laboratories;
- – disease workup was taken from department and
consultations of: surgery, gynaecology, radiation oncology and
chemotherapy. These data were confronted with those collected from
pathology laboratories.
We have excluded:
- – non Tunisian patients;
- – cases of recurrence diagnosed in 2004 whereas the
primitive tumor was detected before that year;
- – patients having a first histopathology-proof prior to
the year of study;
- – patients with bilateral breast cancer were recorded
only one time.
All patient files were reviewed by two doctors. In order to
rectify the histopathology type according to 1988 WHO
classification, most of the biopsies were reviewed. We used the
Scarf-Bloom and Richardson prognostic grading system (SBR).
Data was recorded on a dedicated sheet.
Results
Epidemiology
1437 new cases of invasive breast cancer were diagnosed during the
period of our study. Non invasive breast cancer was diagnosed in 35
cases. Most of the patients were women, with 1408 women versus 29
men. The crude incidence in women was 27.1 with an age-standardized
incidence of 28.5 per 100 000 women.
829 patients had their histopathology or cytology study in
hospital-laboratories versus 459 in private laboratories (table 1).
The mean age of our patients was 51 years and the highest
incidence of breast cancer was between 40 and 54 years old (table 2). 10.2% of the patients were younger
than 35 years old and 2.08% younger than 30 years old. 48%
were postmenopausal and 9.7% were unmarried. 16.5% were nulliparous
and 1% of the women were pregnant at the time of their breast
cancer diagnosis.
Table 1 Women breast cancer distribution private and
public institutions in 2004 and (1994)
- Treatment institution
- Place of first histopathology
|
Hospitals
|
Private sector
|
Total
|
|
Hospital laboratories
|
824 cases (475)
|
5 cases (1)
|
829 cases (476)
|
|
Private laboratories
|
79 cases (50)
|
380 cases (163)
|
459 cases (213)
|
|
Total
|
903 cases (525)
|
385 cases (164)
|
1288 cases (689)
|
Table 2 Incidence of breast cancer in women function of
age
|
Age (years)
|
Number of new cases in 2004* (1994)
|
Crude incidence rate 100 000 women/an in 2004 (1994)
|
|
20-24
|
5 (2)
|
0.99 (0.49)
|
|
25-29
|
23 (16)
|
5.17 (4.21)
|
|
30-34
|
86 (51)
|
22.42 (15.43)
|
|
35-39
|
125 (72)
|
33.69 (25.90)
|
|
40-44
|
234 (120)
|
71.8 (55.02)
|
|
45-49
|
227 (95)
|
81.65 (60.40)
|
|
50-54
|
180 (81)
|
82.95 (58.97)
|
|
55-59
|
115 (64)
|
73.36 (47.91)
|
|
60-64
|
103 (77)
|
79.98 (62.05)
|
|
65-69
|
104 (34)
|
86.46 (41.06)
|
|
70-74
|
64 (24)
|
66.05 (35.49)
|
|
75-79
|
42 (18)
|
72.78 (51.94)
|
|
80 et plus
|
33 (15)
|
55.52 (34.83)
|
|
Total
|
1341 (669)
|
27.11 (15.39)
|
Clinical aspect
44.6% of the patients consulted after a time interval of 3 months.
The major cause of consultation was a tumour with or without
associated symptoms (81.5%). The tumour was more frequently located
in the left breast (51.4 versus 48.6% in the right breast). The
disease was bilateral in 2.6% of the cases. The upper and external
quadrant was the preferential site of the tumour (alone in 32.3%,
associated in 57%). The mean size of the tumour was 40.8 ±
26 mm (34.1 ± 25 mm in patients treated in private
clinics and 42.5 ± 26 mm in patients treated in public
hospitals).
Mammography showed opacity with malignant features in 79.5% of
the cases. According to the 1988 TNM staging system, 12.2% of the
tumours were classified T1, 46.9% T2, 11.2% T3 and 24.7% T4 (6.7%
T4d and 17.6% T4b or c). 13.1% of the patients were metastatic at
initial diagnosis (supraclavicular involvement was considered as a
metastasis according to the same classification).
Pathology
The mean diameter of resected tumours measured by pathologists was
32.7 ± 21 mm which is inferior to the clinical mean-tumour
size (40.8 mm). The mean gross pathological tumour size was
30.18 mm in private laboratories versus 35.16 mm in
hospital laboratories (table 3).
The most frequent histopathological type was invasive ductal
carcinoma representing 86.6% of the cases. Non invasive carcinoma
represents 2.5% only (35 patients), with 94.3% ductal carcinoma in
situ and 5.7% lobular carcinoma in situ. There were 2.9% cases in
private laboratories and 2% in hospital-laboratories.
According to the SBR grading system, grade II was the most
frequent grade (54.5%) followed by grade III (35.2%) and grade I
(9.3%). Axillary’s dissection was performed in 1113 patients, the
mean number of resected nodes was 15, varying from 1 to 61 nodes;
this number was less than 10 in 12.3% of the cases.
Node-involvement was found in 57.1% of the cases, with node-capsule
rupture in 49.5% among them. In 20% of the cases, there were more
than 10 involved nodes.
Hormone-receptors were known in only 938 patients, ie: 66.6% of
the patients. Among these patients, estrogen-receptors were present
in 56.5% and progesterone-receptors in 54.3% of the cases.
Estrogen-receptors were present in 61.4% of postmenopausal women,
and in 51% of premenopausal patients. Progesterone-receptors were
not different between the two groups: 52.1% and 55%,
respectively.
Table 3 Comparison of mean macroscopic tumour size
between private and public sectors in 2004 and (1944)
|
Laboratories
|
- Number of cases
- Diagnosed
|
Tumour size was given in
|
Mean histological tumour size in mm
|
|
Private
|
385 (213)
|
210 (171) cases
|
30.18 + 19 (28.9 ± 18)
|
|
Public
|
903 (476)
|
746 (352) cases
|
35.16 + 24 (37.9 ± 23)
|
Therapeutics
Among non metastatic patients (1290), 1161 received a curative
treatment. Surgery consisted of a mastectomy in 806 patients
(69.4%) and 322 patients (27.7%) were treated by a conservative
surgery. Conservative surgery was more frequently indicated in
private sector since more than one third of the patients received
this treatment: 37 versus 23.6% in public sector.
Breast cancer in men
Breast cancer was diagnosed in only 29 men, during our study
period, which represents 1.97% of all cases. Mean age in this group
of patients was 62.3 years with two peaks of age-interval 45-54 and
70-80 years. In contrast with women population, 17/26 patients were
from rural regions. Time interval between first consultation and
care was 5.5 months and 34.8% of the tumours were of T4b stage,
according to the TNM classification.
Discussion
Epidemiology
In 1994, a large national study on breast cancer was conducted in
Tunisia in order to calculate its incidence and to study its
clinical, anatomopathological and therapeutic features. In 2004, we
carried out a similar study in order to update our information on
the disease situation and to see its evolution during this last
decade. During these two years, there has been a census in the
country which enabled us to calculate the actual incidence of this
disease.
Data were taken from anatomopathological laboratories including
cytology and breast-tumour-biopsies investigations. Cases with no
histopathological proof were excluded (3%) [9].
We observed an increase in the incidence rate from the age of 40
years which continues untill the age of 55 years, whereas in 1994,
there were two distinct peaks of incidence rate in 45-49 and 60-64
years [1].
The age-standardized incidence of breast cancer has almost
doubled since 1994 (28.5 per 100 000 women in 2004 versus 16.7 in
1994). Despite this alarming increasing rate, our incidence remains
inferior to others reported in several cancer registries [6-8, 10,
11].
We can state that breast cancer remains less frequent in Tunisia
than in European countries: for example, our incidence is almost
the half of the incidence in Spain (45.8) and is almost one third
of the breast cancer incidence in Denmark and Sweden [12]. In
Kuwait and Arabian Gulf, the standerdized incidence of the period
1992-1993 is not far from ours in 2004 (32.8 for Kuwaitian women)
[8]. In the same way, we notice that our incidence is not different
from Algerian’s (table 4).
These epidemiological differences may be due to environmental,
genetical and nutritional factors. In fact, breast cancer incidence
rates vary between different regions of the world. It is
particularly high in North America and North Europe, intermediate
in South Europe and South America and low in Asia and Africa
[8].
The unexpected increase of the incidence observed from 1994 to
2004 in our study, was also noticed in several countries in Asia
[11].
Some risk factors such as nulliparity (16.5% in 2004 and 14.3%
in 1994) and an advanced age of first pregnancy, after the age of
30 years old (18.9% in 2004 and 12.9% in 1994) were observed in our
study which correlates with data in the literature. Breast cancer
during pregnancy represents 1% which is similar to the rate
reported by Merviel and all. [14].
Table 4 Age-standardized rate of breast cancer in women
observed in some countries [4, 12, 13]
|
Country
|
Age-standardized rate per 100 000 women (population model = world
population)
|
|
France (Somme 1993-1997)
|
82.1
|
|
Belgium (Flandre 1997-1998)
|
88.1
|
|
Denmark (1993-1997)
|
88.3
|
|
Germany (1993-1997)
|
71.4
|
|
Italy (North East 1995-1997)
|
79.2
|
|
Portuguese (1993-1997)
|
47.1
|
|
Spain (Grenad 1993-1997)
|
45.8
|
|
Kuwait (1994-1997)
|
34.3
|
|
Japan (Osaka 1993-1997)
|
27.9
|
|
Algeria (Alger 1993-1997)
|
21.3
|
|
Tunisia (1994)
|
16.7
|
|
Tunisia (2004)
|
28.5
|
Clinical aspects
According to TNM classification, T2 stage was the most frequent
representing 46.9% of the cases. T1 tumours accounted for only
12.2%, while T4 tumours represented 24.7% with 17.6% T4b and 6.7%
T4d tumours. In the literature, T4d tumours vary from 2 to 5% of
all breast cancer [15]. In the United States for example, 1 to 6%
of breast cancer are T4d [15].
During the 1970s and the 1980s, the PEV classification which
characterizes inflammatory forms of breast cancer, was used at the
ISA institution, in addition to the TNM. Tumours with localized
inflammation are called pev2, those with diffuse inflammation,
pev3. Inflammatory form was initially individualised as particular
disease by French authors, but this is not admitted by other
authors [15-17].
’PEV-tumours’ or locally advanced tumours used to be considered
as a Tunisian particularity [2, 4, 10, 11, 16, 18, 19]. table 5 shows a comparison between our results with
those of a previous study carried out at the ISA institute
including 581 breast cancer cases diagnosed between 1969 and 1974
[4]. We notice that:
- – PEV2 and PEV3 tumours represent 24.3% of the cases in
our study while they were 55.2% in the other series [4]. This
proportion is constant for the last decade.
- – In comparison with our results, PEV3 or T4d forms in
the previous study were by far more frequent: respectively 48.7
versus 6.2% and 6.7% in the 1994 and 2004 two large studies [1,
20].
These differences may be explained by different hypotheses:
- - There may be an actual decrease in the frequency of
this particular form.
- - The use of two different staging systems for these
studies may be a cause of error in the evaluation of these forms
since the definition of corresponding stages is not well
established.
Comparing the TNM stages between the different institutions
(table 6), we noticed that:
- – There are more T1 tumours in private sector than in
the public one. This difference was also noticed in the previous
study: 20.7% and 17% in private sector versus 3.3% and 11.2% in
public sector, for the years 1994 and 2004 respectively [1].
- – T4b stage rate is almost constant for the two studies
with a higher frequency for patients in public hospitals: 19.8 and
19.4% versus 3.3% and 7.7% in 1994 and 2004, respectively [1].
- – Metastatic breast cancer in private sector counted for
only 6.9% in 1994 and 12% in 2004. This rate was very low in
comparison with that of public sector which was 26.2% in 1994 and
14.4% in 2004 [1]. This difference may be explained by two
different factors:
- . Time interval between consultation and treatment is
shorter for patients treated in private sectors (this is reflected
by a smaller mean-tumour size), which correlates with lower
metastasis rate.
- . Disease workup may be more complete for patients
treated in public hospitals.
We think that these two causes are both associated for this
group of patients.
Table 5 Locally advanced breast cancer: a comparison
between different Tunisian studies
|
Stage
|
ISA (1969-1974) (1)
|
Tunisia 1994 * (13)
|
Tunisia 2004
|
|
PEV 2
|
6,5%
|
17%
|
17.6%
|
|
PEV 3 (T4d)
|
48,7%
|
6,2%
|
6.7%
|
|
Total des cas
|
581
|
659
|
1068
|
Table 6 T, N and M distribution between private and
public sectors
|
TNM classification
|
Public sector
|
Private sector
|
|
T0
|
3,8%
|
8,1%
|
|
T1
|
11,1%
|
17,3%
|
|
T2
|
46,6%
|
51,4%
|
|
T3
|
11,1%
|
11,8%
|
|
T4a
|
0,4%
|
0%
|
|
T4b
|
19,4%
|
7,7%
|
|
T4c
|
0,5%
|
0,4%
|
|
T4d
|
7,1%
|
3,2%
|
|
N0
|
28,7%
|
48,9%
|
|
N1
|
65,5%
|
48,1%
|
|
N2
|
5,8%
|
2,9%
|
|
N3
|
0%
|
0%
|
|
M0
|
85,6%
|
95,6%
|
|
M1
|
14,4%
|
4,4%
|
Pathology
Comparing the different histopathology-type rates, we notice that
our results are similar to those described in the literature and
those of the ISA studies between 1969 and 1985 [6, 16, 20].
The pathological mean tumour size is different between private
and public sectors. This may be due to two reasons:
- - A higher social, economical and educational level in
patients treated in private sector. These patients consult their
doctor earlier.
- - The second reason is that the treatment is started
earlier in private sector. In fact, the waiting list is usually
longer in public hospitals than in private sector.
Comparing our results with the data of the ISA institute for the
period 1969 to 1985, we notice that the rates of the SBR grade I,
II and III are stable [1, 21]. They represent 10.3, 45.5 and 35.2%
respectively, for the two periods. There is no difference in the
SBR-grade rates between the patients treated in private sector and
those of the ISA institute.
Tumour-size evaluation
Comparing the mean tumour size found at the ISA institute in the
period 1969-1974 (63.9 mm) with that of the period 1981-1985
(55.8 mm) we notice a decrease of 8 mm [20]. The same
decrease rate is noticed in the country during the last decade. The
last two large studies that included all breast-cancer patients
diagnosed in Tunisia in the years 1994 [1] and 2004, showed a
decrease in tumour size from 49.53 to 40.76 mm (a difference
of 8.7 mm). Considering the relatively high mean tumour size
for the year 2004, we can say that this decreasing rate is low. The
rate of conservative treatment has increased in the same way during
the last 10 years, since 27.7% of the patients treated in 2004 have
received a conservative treatment versus 17.6% in 1994 and only 4%
in the period 1980 to 1987 [1, 3].
Conclusion
This second national study on breast cancer confirmed an actual
increase in the incidence of this first-cancer in women. However,
the frequency of breast cancer in Tunisia remains low compared with
developed countries. The large tumour size at diagnosis and the
relatively younger mean age of our patients are the two major
points to be considered in the Tunisian national cancer program.
Inflammatory breast cancer which was thought to be a Tunisian
particularity, showed a decreasing rate during the last decade.
This entity which was considered as a Tunisian particularity was
overestimated in previous studies since some locally advanced
tumours called so were real locally advanced tumour (T4b).
From this experience, we can say that, in countries with no
cancer registry, such punctual studies which are not very
expensive, may be a serious source to know the trends of more
common cancer epidemiological features.
Acknowledgment
We thank all the doctors of private and public practice for their
precious collaboration: K. Abdelmajid, S. Belhassen,
F. Ben Ayed, M. Ben Ayed, Y. Ben Hamed, S. Ben
Jilani, R. Ben Youssef, N. Bouaouina, S. Boubaker,
A. Boudawara, C. Bouzakoura, M. Cammoun, S. Chatti, H. Chelli,
K. Dallagi, J. Daoud, M. Essakly, A. Falfoul,
M. Hechiche, G. Jerbi, R. Jlidi, N. Kamoun,
H. Khairi, A. Khattech, K. Khodjet, A. Khil, S.
Korbi, A. Koubaa, MK Makni, S. Mzabi, L. Ouertani, H.
Oueslati, K. Rahal, S. Rekik, H. Rezigua, M. Saguem, F.
Sellami, R. Sfar, M. Suissi, A. Zakhama, M. Zitouna, F. Zouari
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