Radiol Oncol 2020; 54(3): 335-340. doi: 10.2478/raon-2020-0040
335
research article
Breast cancer risk based on adapted IBIS 
prediction model in Slovenian women aged 
40–49 years - could it be better?
Tjasa Oblak4, Vesna Zadnik1,2, Mateja Krajc3,4, Katarina Lokar1, Janez Zgajnar2,5
1 Epidemiology and Cancer Registry, Institute of Oncology Ljubljana, Ljubljana, Slovenia
2 University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia
3 Cancer Genetic Clinic, Institute of Oncology Ljubljana, Ljubljana, Slovenia
4 Faculty of Health Sciences, University of Primorska, Izola, Slovenia
5 Department of Surgical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
Radiol Oncol 2020; 54(3): 335-340.
Received 25 March 2020
Accepted 7 May 2020
Correspondence to: Prof. Janez Žgajnar, M.D, Ph.D., Department of Surgical Oncology, Institute of Oncology Ljubljana, Zaloška cesta 2, 
SI-1000 Ljubljana, Slovenia. E-mail: jzgajnar@onko-i.si
Disclosure: No potential conflict of interest were disclosed.
Background. The aim of the study was to assess the proportion of women that would be classified as at above-
average risk of breast cancer based on the 10 year-risk prediction of the Slovenian breast cancer incidence rate 
(S-IBIS) program in two presumably above-average breast cancer risk populations in age group 40-49 years: (i) women 
referred for any reason to diagnostic breast centres and (ii) women who were diagnosed with breast cancer aged 
40–49 years. Breast cancer is the commonest female cancer in Slovenia, with an incidence rate below European av-
erage. The Tyrer-Cuzick breast cancer risk assessment algorithm was recently adapted to S-IBIS. In Slovenia a tailored 
mammographic screening for women at above average risk in age group 40–49 years is considered in the future. 
S-IBIS is a possible tool to select population at above-average risk of breast cancer for tailored screening.
Patients and methods. In 357 healthy women aged 40–49 years referred for any reason to diagnostic breast cen-
tres and in 367 female breast cancer patients aged 40–49 years at time of diagnosis 10-years breast cancer risk was 
calculated using the S-IBIS software. The proportion of women classified as above-average risk of breast cancer was 
calculated for each subgroup of the study population.
Results. 48.7% of women in the Breast centre group and 39.2% of patients in the breast cancer group had above-
average 10-year breast cancer risk. Positive family history of breast cancer was more prevalent in the Breast centre 
group (p < 0.05).
Conclusions. Inclusion of additional risk factors into the S-IBIS is warranted in the populations with breast cancer 
incidence below European average to reliably stratify women into breast cancer risk groups.
Key words: breast cancer; early detection; risk prediction model; tailored screening
Introduction
Breast cancer is the most common cancer in wom-
en with more than 2 million new cases diagnosed 
worldwide in the year 2018 and therefore represents 
a major public health problem. In Europe alone, the 
number of women diagnosed with breast cancer in 
2018 was approximately 523 000 with an estimated 
age-standardized incidence rate of 100.9/100 000.1 
Breast cancer is the most common cancer in women 
in Slovenia as well and in 2016 there were 1386 new 
cases diagnosed. However, the age-standardized 
incidence rate in Slovenia is lower than European 
average rate (68.5/100 000 women).2,3
Mammographic screening is one of the estab-
lished strategies to deal with the breast cancer 
problem in public healthcare. The Slovenian na-
tional mammographic screening program offers 
biennial screening mammography to all women in 
the age group 50–69 years.4 
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Oblak T et al. / Breast cancer risk based on adapted IBIS prediction model336
However, approximately one sixth of breast 
cancer patients are diagnosed at age 40 to 49 years, 
on average with a more advanced stage at the time 
of diagnosis compared to patients diagnosed in 
the age group 50–69 years.2 Despite this fact, in 
Slovenia there is no organized mammographic 
screening program in this age group of women 
due to lack of convincing evidence that population 
mammographic screening reduces breast cancer 
mortality in women aged 40–49 years. Namely, ac-
cording to European guidelines there is condition-
al recommendation against breast cancer screening 
for women aged 40 to 45 years, and only condition-
al recommendation for the screening for the age 
group 45 to 49 years.5 
In Slovenia all breast cancer in the age group 
40–49 years are diagnosed in regional diagnostic 
breast clinics whether due to symptomatic disease 
or as a result of opportunistic screening. Women 
can be referred to opportunistic screening by their 
gynaecologists or general practitioners based on 
family history of breast cancer or other risk factors. 
Women with high breast cancer risk (i.e. genetic 
predisposition) may opt for surveillance separately 
in a dedicated centre.
To overcome the limitations of the population 
screening in younger women, tailored breast can-
cer screening limited to women with an above-
average breast cancer risk is one of the research 
options today. Based on the 2018 Slovenian recom-
mendations on breast cancer prevention and treat-
ment a tool is needed to stratify women according 
to 10-years breast cancer risk in three groups: pop-
ulation risk, moderately increased risk and high-
risk group, respectively.6 Only women at above the 
population risk should be offered screening before 
the age of 50. 
To improve identification of women at above-
average risk of breast cancer, many breast cancer 
prediction models have been developed in the last 
three decades.7 The IBIS software, based on the 
Tyrer-Cuzick algorithm, is one of the most consist-
ent, both in the general population and in familial 
setting.8-10 IBIS calculates breast cancer risk based 
on classical risk factors including age, family histo-
ry of breast or ovarian cancer in first- and second-
degree relatives, age at menarche and menopause, 
parity and age at first childbirth.8 Recently mam-
mographic density and polygenic risk score were 
added as additional risk factors to be taken into 
account in the calculation of breast cancer risk.11,12 
However, these two risk factors are very seldom 
available in routine clinical setting. The IBIS pro-
gram was developed with breast cancer incidence 
rates of the United Kingdom and was recently 
separately adapted for the Swedish and Slovenian 
populations (S-IBIS software).13
The IBIS program was validated on several 
populations, varying both in age and geographic 
location.7,9,10,14,15 However, the performance of the 
recently adapted S-IBIS in Slovenian population is 
still unknown. We were particularly interested in 
S-IBIS performance in two presumably above the 
average breast cancer risk populations: (i) women 
aged 40 to 49 years referred for any reason to di-
agnostic breast centres and (ii) women who were 
diagnosed with breast cancer between the ages of 
40 to 49.
The aim of our study was to conduct S-IBIS 
calculations in the two aforementioned groups of 
patients and determine the proportions of three 
10-years breast cancer risk groups (population risk, 
moderately increased and high risk) in both group 
of patients.
Patients and methods
In this study two groups of patients were included:
1. 357 women aged 40–49 years attending oppor-
tunistic screening in 5 diagnostic breast centres 
in central Slovenia in year 2014;
2. 367 women aged 40–49 at time of breast cancer 
diagnosis, treated at the Institute of Oncology 
Ljubljana between 2014 and 2019. Patients are 
regularly followed up in outpatient clinics of the 
Institute of Oncology Ljubljana.
All women were asked to answer a question-
naire about established risk factors for breast cancer 
according to the IBIS requirements and family his-
tory of breast and ovarian cancer concerning first- 
and second-degree relatives (Table 1). Women in 
the breast cancer group were specifically asked to 
provide data available at their age of 40. Personal 
history of breast cancer diagnosis was not included 
in the risk calculation for the breast cancer group. 
Mammographic density and polygenic risk score 
could not be included in the risk calculation due 
to unavailable data, therefore these fields were left 
blank. Results of genetic testing were also not in-
cluded as the testing was usually performed after 
the diagnosis of breast cancer in the breast cancer 
group. Women from the Breast centre group did 
not fill the criteria for genetic testing and the test-
ing was therefore not performed.
Women with known genetic predisposition (i.e. 
BRCA and other mutations) were not included in 
the study. The majority of women who are carriers 
Radiol Oncol 2020; 54(3): 335-340.
Oblak T et al. / Breast cancer risk based on adapted IBIS prediction model 337
of a hereditary breast cancer related mutations are 
already followed up in a dedicated centre and they 
would not benefit from an improved population 
screening but may ultimately alter the proportion 
of women in the low and high-risk groups.
The participants were informed about the mean-
ing and use of the provided data and signed an in-
formed consent.
Based on the acquired data 10-year risk of breast 
cancer for each woman with the S-IBIS software 
was calculated. 
For the purpose of a separate sub analysis the 
patients were divided in two subgroups, age 40–44 
and age 45–49. In the breast cancer group there 
were 125 participants in the 40–44 years age group 
and 242 participants in the 45–49 years group, 
while in the breast centre group there were 153 
participants in the 40–44 years age group and 204 
participants in the 45–49 years group.
In breast cancer patient group the personal di-
agnosis of breast cancer was not included in the 
calculation of risk.
Breast cancer risk thresholds for the Slovenian 
population as described in the literature (popula-
tion risk: below 2%, moderately increased risk: 
2–6.5%, high risk: above 6.5%) were taken into ac-
count for assessment of performance of the S-IBIS 
software.13
IBM SPSS Statistics v25 was used to generate 
data analysis. Mann-Whitney and Chi-square tests 
was used to assess statistically significant differ-
ences in baseline data; p < 0.05 was considered sta-
tistically significant.
The study was approved by the National Ethics 
Committee.
Results 
The baseline characteristics of the two groups re-
garding the breast cancer risk factors are report-
ed in Table 2. Statistically significant differences 
where noticed between the two groups while an-
alysing age, body mass index (BMI) and positive 
family history for breast and/or ovarian cancer, 
with participants in the Breast centre group being 
younger, with higher BMI and positive family his-
tory in more cases.
The risk calculations for the whole popula-
tion and within each age subgroup are shown in 
Table 3.
Discussion
S-IBIS risk calculation based on the included par-
ticipants’ data identifies only 48.7% of women re-
ferred to Breast centres as above population breast 
TABLE 1. Breast cancer risk factors used for 10-year breast 
cancer risk calculation with S-IBIS software
Risk factor
Age (years)
Height
Weight
Age at menarche (years)
Age at first childbirth
Menopausal status
Hormone replacement therapy use
Benign breast disorder
Family history of breast cancer (breast cancer in first- 
and second-degree relatives and age at presentation)
Family history of ovarian cancer (ovarian cancer in first-
degree relatives and age at presentation)
TABLE 2. Baseline characteristics of participants 
Breast cancer 
group
Breast Centre 
group
Age (yaars, mean)* 45.6 44.8 
BMI, mean (kg/m2)* 24.3 24.8
Age at menarche (years, mean) 13.0 13.0 
Nulliparity 10.5% 11.1%
Age at first childbirth (years, mean) 23.0 23.4 
Positive family history for breast 
and/or ovarian cancer* 48.8% 56.6%
*  statistically significant difference was observed between the two groups (p < 0.05); BMI = Body 
mass index
TABLE 3. Risk stratification for all participants and for age subgroups 40–44 years 
and 45–49 years based on S-IBIS calculation for breast cancer patients and women 
screened in Breast centre; risk categories for women aged 40 to 49 as in 2018 
Slovenian guidelines
Population 
risk 
(< 2 %)
Moderately 
increased risk 
(2–6.5 %)
High risk
(> 6.5 %)
Breast cancer group - 10-year 
breast cancer risk (age 40–49) 60.8 % 37.8 % 1.4 %
Breast centre group - 10-year 
breast cancer risk (age 40–49) 51.3 % 47.6 % 1.1 %
Breast cancer group - 10-year 
breast cancer risk (age 40–44) 64.0 % 34.4 % 1.6%
Breast centre group - 10-year 
breast cancer risk (age 40–44) 58.2% 41.8 % 0.0%
Breast cancer group - 10-year 
breast cancer risk (age 45–49) 59.1 % 39.7 % 1.2 %
Breast centre group - 10-year 
breast cancer risk (age 45–49) 46.1 % 51.9% 2.0%
Radiol Oncol 2020; 54(3): 335-340.
Oblak T et al. / Breast cancer risk based on adapted IBIS prediction model338
cancer risk (10 years risk > 2%). Furthermore S-IBIS 
as used in our study identifies as above the popu-
lation risk 39.2% of women, who were diagnosed 
with breast cancer. It should be once again noted 
that some data such as mammographic density and 
polygenic risk score (PRS) that could be included in 
the risk calculation, could not be retrieved for the 
participants of our study. Still, the identification of 
almost 40% breast cancer patients as at above-aver-
age risk is a promising result, that is comparable to 
results of other studies.10, 16-19 However it is still wor-
risome that as much as 60% of patients diagnosed 
with breast cancer in age group 40–49 would be di-
agnosed outside the screening program if women 
were invited to breast cancer screening based on 
S-IBIS risk calculation as it could be widely avail-
able at the present moment (that is, without data 
about mammographic density and PRS). Therefore 
our study showed that tailored mammographic 
screening in the age group 40–49 in Slovenian 
population cannot be organized based on this form 
of S-IBIS alone. Assuming the expected less than 
100% attendance rate of the invited population and 
lower mammography sensitivity in this age group, 
the proportion of diagnosed cancers would be even 
lower. These data are in clear contrast to current 
Slovenian screening program in age group 50–69 
in which 70% of all cancers in this age group are 
diagnosed within the screening program with an 
average 75% attendance rate.2 
Interestingly, a higher proportion of women 
were identified as above population risk in healthy 
women referred to breast centres for opportunis-
tic screening compared to breast cancer patients, 
48.7% vs. 39.7%, respectively. One of the reasons 
could be the higher proportion of women with 
positive family history and higher BMI in the 
breast centre group. The reason for relatively poor 
performance of the S-IBIS could be caused also by 
some personal characteristics of Slovene women 
that differ from other European populations where 
IBIS was validated, e.g. the age at first childbirth in 
Slovenia is lower than European average.20
When analysing the S-IBIS performance sepa-
rately in the 40–44 year and 45–49 year age sub-
groups, we found that S-IBIS performed slightly 
better in the age group 45–49 years compared to 
younger age group (40–44 years). The difference 
was not big enough however to allow to draw dif-
ferent conclusions between the subgroups studied.
Extension of mammographic screening to wom-
en younger than 50 is a matter of debate, although 
several studies have confirmed that the harms 
of early screening do not outweighs the benefits. 
Over-diagnosis and false positive recalls in women 
younger than 50 years and non-significant lower 
breast cancer mortality between younger and older 
breast cancer patients make early breast cancer 
screening unreliable and unadvisable in the gen-
eral population.21,22 However, the problem of early 
detection of breast cancer in women younger than 
50 persists and as previously stated, screening of 
women at higher-than-average risk of breast can-
cer seems one of the most feasible solutions. Based 
on data presented, further steps in refining a breast 
cancer risk calculation tool will have to be done 
before a tailored screening is implemented, as the 
inclusion of more breast cancer risk factors like 
mammographic density. Mammographic density 
is considered as a strong risk factor for breast can-
cer and, as already mentioned, can be included in 
the S-IBIS calculation.23-25 Another promising risk 
factor is the polygenic risk score (PRS) based on 
the presence of single nucleotide polymorphisms 
(SNPs) related to breast cancer risk and which can 
be also included in the S-IBIS calculation.26-28 At 
the present moment, there are numerous differ-
ent sets of SNPs being studied worldwide, none of 
them yet approved to routine use. Of note, several 
studies in European populations with higher than 
Slovenian breast cancer incidence have shown that 
both factors independently increase the sensitivity 
of IBIS.27-30 Due to technical limitations both mam-
mographic density and PRS are not routinely in-
cluded in S-IBIS calculations throughout Slovenia, 
therefore currently no data on value of mammo-
graphic density and PRS in Slovenian population 
is available. Data are available for selected breast 
centres and are yet to be analysed at the time writ-
ing this article. Studies with S-IBIS risk calcula-
tions that include these risk factors are necessary 
and will have to be performed to further improve 
the stratification of women in the breast cancer risk 
groups and reveal the true potential of the S-IBIS 
program. 
Our study had several limitations. Since it is a 
cross-sectional study, it lacks follow up and we 
could not observe the eventual crossover between 
the two groups. Only follow-up of the Breast cen-
tre group until the age of 50 would reveal the per-
cent of overlap between the two groups and the 
true quality of risk stratification based on risks 
calculated by S-IBIS. Due to inability to assess the 
proportion of women undergoing early screening 
that would develop breast cancer before the age of 
50, statistical comparison between the two groups 
was not performed, as it would lead to false as-
sumptions. Furthermore, the non-systematic ac-
Radiol Oncol 2020; 54(3): 335-340.
Oblak T et al. / Breast cancer risk based on adapted IBIS prediction model 339
crual of women referred to opportunistic screening 
in Breast centres can result in high proportion of 
women at average breast cancer risk in the Breast 
centre group. Despite these limitations however, 
our study demonstrated the inability of the S-IBIS 
alone to reliably stratify women between the breast 
cancer risk groups. We acknowledge that a pro-
spective study would give clearer and more reli-
able data, but in the given settings only a retrospec-
tive analysis was possible and perhaps necessary 
to plan a valid perspective study.
Conclusions
In conclusion, risk stratification based on S-IBIS 
calculation confirmed that at least half of women 
referred to regional Breast centres have above-
average 10-year breast cancer risk and are entitled 
to regular screening prior to age 50 according to 
Slovenian guidelines. However, more than half of 
breast cancer patients aged 40–49 would not be se-
lected for early tailored screening based on S-IBIS 
calculations with the chosen risk factors. Inclusion 
of additional risk factors (as mammographic breast 
density or PRS) into the S-IBIS is warranted in the 
populations with breast cancer incidence below 
European average to reliably stratify women into 
breast cancer risk groups. Tailored mammography 
screening in age group 40–49 based on S-IBIS alone 
can not be organized.
Acknowledgment
The study was supported by the research program 
of the Slovenian research agency P3-0352.
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