Introduction
Breast cancer, especially postmenopausal, is the most occurring cancer in women worldwide and the second leading cause of female cancer death [
1]. In Western Europe, one in eight women develops breast cancer during her lifetime, of whom more than 75 % after the age of 50 [
2]. The high burden of disease and associated treatment costs makes postmenopausal breast cancer a major public health issue. Not only incidence rates differ according to menopausal status, but effects of some risk factors are also modified by menopausal status. For example, overweight has no or even a small protective effect in premenopausal women, while it increases risk after menopause [
3].
Several established risk factors for postmenopausal breast cancer are not, or rather difficult, to modify when the age of 40 has been reached, e.g. age at menarche, parity, age at first child birth and duration of breastfeeding. As lifestyle is modifiable, it provides an opportunity for primary prevention. Overweight and obesity, physical inactivity, alcohol consumption, smoking and low dietary fibre intake are all associated with an increased breast cancer risk after menopause [
4‐
7] and are still present and modifiable at a later age.
The potential impact of preventive measures can be assessed by computing the population attributable fraction (PAF). This fraction represents the proportion of cases in a population that could be prevented if exposure to a causal factor had not occurred [
8].
This research is the first to describe the situation for the Netherlands regarding exposure to lifestyle-related risk factors and breast cancer occurrence. We computed individual and combined PAF estimates for the above five lifestyle-related risk factors for the Netherlands, a country with one of the highest incidence rates of breast cancer worldwide [
1].
Discussion
Our results imply that approximately one out of four postmenopausal breast cancer cases in women aged >50 years in 2010 was attributable to lifestyle factors as present at age 40 and older. Overweight/obesity (8.8 %) contributed the most, followed by alcohol consumption (6.6 %), physical inactivity (5.5 %), smoking (4.6 %) and suboptimal dietary fibre intake (3.2 %). These estimates were based on comprehensive and up-to-date literature and matched with detailed prevalence rates of risk factor exposure in the Netherlands.
Estimations of the attribution of these modifiable lifestyle risk factors to postmenopausal breast cancer have not been described for the Netherlands previously. Furthermore, in this research, we replicated the results of other western European countries of population attributable risks of lifestyle-related risk factors for breast cancer.
Strengths of our study include detailed data on prevalence of risk factor exposure, allowing us to use continuous RRs that ensured little loss of information. In addition, we used RRs which were derived from recent meta-analyses [
4‐
7] evaluating multiple studies with risk estimates that were adjusted for several confounders, including lifestyle-related risk factors. Furthermore, Monte Carlo simulations were performed to compute 95 % confidence intervals for the PAF estimates, incorporating imprecision in RRs (defines by the literature derived 95 % confidence intervals of the RR estimates) and prevalence rates (including the most detailed prevalence rates available for levels of exposure, for example, for alcohol we used prevalence rates per each glass/day also for the exposure levels >4 glasses/day).
However, there are also some limitations. We cannot rule out possible residual confounding which could have influenced our PAF estimates. However, since the literature-derived RRs incorporated in the meta-analyses usually are adjusted for most important confounders, it is unlikely that remaining unmeasured confounders influenced the results considerably. Simulation studies show that estimates which are corrected for major confounders are affected minimally after additional correction for more possible confounders [
18]. Nevertheless, measuring lifestyle habits in a valid way is difficult due to measurement errors in assessing the confounders.
Prevalence rates were based on self-reported exposure. Misclassification (most likely due to underreporting of exposure) may have led to an underestimation of our PAFs. Also, the prevalence rates were measured in a subsample of people, wherein response rates were high (60 %) but not 100 %. Therefore, also participation bias may have affected the results. Furthermore, we included exposure to risk factors from age 40 on only, while it is also likely that not only short-term, but also life-long exposure to lifestyle-related risk factors, or exposure during a critical period of life (e.g. between menarche and first childbirth) contributes to a higher breast cancer risk [
19]. However, there is still much uncertainty around the latency period and which period in life is most influential.
In comparable research, hormone replacement therapy (HRT) is often included as a risk factor. Although RRs of 1.10 to 1.66 have been described for current HRT use [
20,
21], we did not include this factor in our analysis. In 2001, the estimated prescription of HRT in women > 40 in the Netherlands was 5.6 % and dropped to 2.4 % in 2004 [
22]. Currently, prescriptions are close to zero [
23]. As shown by the Million Women study, the increased risk of breast cancer caused by HRT almost disappears after 5 years of cessation [
21], meaning that HRT use (past and current) barely influences breast cancer incidence in the Netherlands anymore.
Attributable fractions of modifiable risk factors for all age breast cancer have been estimated for several countries in Europe, reaching up to 25 % in the UK and Germany [
24,
25]. However, different sets of risk factors were considered, making results difficult to compare.
Regarding the whole of Europe, Soerjomataram et al. [
26], estimated the number of excess cases, i.e. avoidable breast cancer cases, by comparing a countries all-ages incidence rate to the lowest incidence rate in a European country (the baseline incidence rate). For the Netherlands, they estimated around 30 % of all age breast cancer to be avoidable, which was comparable to their estimates for other Western and Northern European countries, but much higher than estimates for Eastern (i.e. Czech Republic, Romania, Lithuania; up to approximately 5 %) and Southern Europe (i.e. Spain, Portugal; up to approximately 15 %). The authors speculate that this higher incidence rate could be caused by over-diagnosis due to extensive screening programmes and higher exposure to reproduction-linked risk factors. Even though these estimates cannot be directly compared to our PAF numbers, as they used a different methodology, it gives us an idea about the Dutch situation in proportion to the rest of Europe with regard to avoidable cancer cases. And although their number refers to all age breast cancer, it will largely refer to postmenopausal breast cancer as most cases occur after age 50.
We included five lifestyle-related risk factors for postmenopausal breast cancer for which a large body of evidence is available and that occur with substantial prevalence rates in middle-aged women in the Netherlands.
Fibre intake and smoking are not, or seldom, considered when estimating PAFs for breast cancer. Since there is emerging strong evidence that these factors increase breast cancer risk, we included these factors and recommend including them in future studies. A recent Canadian study that included smoking as a risk factor reported a PAF of 3–4 % based on prevalence rates of risk facture exposure in the years 1994–2006 [
27].
Overweight and obesity, alcohol consumption and physical inactivity are often included in other studies. Considering these three factors, we estimate a combined PAF of around 20 %. Similar results were found for neighbouring countries. Parkin et al. estimated that 17 % of all breast cancer cases, irrespective of age, in 2011 were attributable to these factors in the UK [
24]. Barnes et al. estimated a PAF of 21 % for Germany in 2010 [
25]. However, we observed some differences for the separate risk factors. PAF estimates for a BMI > 25 kg/m
2 vary from 2.5 % in Germany [
25], to 5.6 % in France [
28] and 8.7 % in the UK [
29], the latter being comparable to our estimate (8.8 %). The attribution of overweight/obesity has previously been computed for the Netherlands. Bergstrom et al. estimated a PAF of 6.3 % based on a 42 % exposure rate in the years 1993–1996, and similar RRs as we used [
30]. Since the prevalence of overweight/obesity is still increasing in the Western world, the PAF is doing so concordantly.
For alcohol consumption, similar PAFs, ranging from 6.4 to 9.4 %, are described in adjacent countries [
25,
28,
31]. However, PAFs for alcohol consumption differ in other developed countries as the US and Australia, where PAFs reach up to maximum 3 % [
27,
32,
33]. Consumption of alcohol by European women is rather high; 75 % of Dutch women >40 years drink on a regular basis.
For physical inactivity, mainly higher PAF estimates than ours (5.5 %) were reported in Europe, of around 10–14 % [
25,
28,
34], except for the UK (3.4 %) [
35]. Numbers in the U.S. even rise up to 16 % [
36]. Differences in prevalence rates largely explain this variation, i.e. in the U.S., 78 % of women were considered physically inactive, versus 56 % in the Netherlands. Another explanation why estimates vary greatly could lie in the fact that PAFs are sensitive to differences in risk category definitions with their accompanying RR [
37]. Due to the great difficulty of measuring activity levels and determining proper risk categories, other definitions for physical inactivity and RRs are used in literature. Also, we did not incorporate intensity of activities.
In the Netherlands, incidence of breast cancer is among the highest worldwide. We estimated that approximately 25 % of postmenopausal breast cancer is associated with lifestyle behaviour at age 40 years. Reproductive factors and hormones will be associated with another proportion of cases, but these are less modifiable. Still, there is a substantial proportion of cancers that seem to occur at random [
38]. However, we should also not exclude the possibility of yet undetected exposures, such as naturally occurring estrogens in the environment; or other chemicals with estrogenic function.
Often, success rates of lifestyle modifying programmes are limited. Therefore, for the Netherlands, a 25.7 % reduction in postmenopausal breast cancer incidence would be the maximum to be achieved, rather than realistic. However, these estimates may help motivating women as well may they inform policy makers about which risk factors should be addressed first.
To conclude, our results imply that one in four postmenopausal breast cancer cases in the Netherlands in 2010 is attributable to five strongly associated lifestyle-related risk factors. These risk factors are excess body weight, an inactive lifestyle, alcohol consumption, smoking and low dietary fibre intake.