Demystifying Breast Cancer Incidence in Europe: An Integrative Analysis of Socioeconomic, Regional, and Lifestyle Factors

 
 

Demystifying Breast Cancer Incidence in Europe: An Integrative Analysis of Socioeconomic, Regional, and Lifestyle Factors

Rakshita Raajesh, Tushita Bordoloi (Equal contribution),

and Dr Lopamudra Das Roy

Published: October/2023

@BreastCancerHub, All Rights Reserved

Abstract

Background: Breast cancer incidence and mortality rates in Europe have been rising over the years at an alarming rate. There are many dynamic factors contributing to this epidemic and there are preventative measures we can implement to mitigate these surging incidence and mortality rates among the European population. Aim: Our aim is to spread awareness about potential risk factors, delineate the reason cancer rates have been drastically increasing by comprehensively analyzing a variety of factors, and devise ways to prevent the surge in incidence/mortality rates. Methods: Most of the information provided has been derived from PubMed and resources from reliable Cancer institutes and governmental databases such as the European Commission official website. Discussions: The causes for cancer can be attributed to demographic, regional, socioeconomic, and genetic differences among the continent of Europe. Conclusion:  In order to prevent the rise in cancer cases, European countries must modify factors pertaining to lifestyle, occupational experiences, and the consumption of alcohol and tobacco. European governments must implement efforts to equalize access to healthcare, which will result in higher screening rates and holistic treatment plans.

Introduction

The drastic increase in the number of breast cancer cases in Europe poses a detrimental threat to the public. In fact, Breast cancer was the leading cause of death from cancer in women with a whopping 138,000 deaths among 40 European countries in 2018 [1]. This surge in breast cancer cases in Europe can be attributed to the inherent socioeconomic, demographic, and biological disparities among various regions, resulting in differences in the implementation of screening methods and treatment plans. By shedding light on these disparities, we hope to uncover potential reasons for the rising number of breast cancer cases and mortality rates which will allow for the emergence of solutions that address these reasons. Analyzing these disparities along with key risk factors pertinent to the development of breast cancer in the European Union will provide adequate reasoning for the heightened risk of breast cancer in Europe.

Prevention and Screening

The European Society for Medical Oncology (ESMO) recognizes the growing number of breast cancer cases in the European Union and acknowledges that mammography screening is the most effective method for early detection. In fact, the European Union strongly suggests a 70-75% participation rate in screening methods among the eligible population [2]. The ESMO recommends that women between the ages of 50 and 69 attend a mammogram screening every 2 years while women of ages 70-74 attend a screening every 3 years [2] since mammography has been shown to lower breast cancer mortality by 40% [3]. However, only 66% of women aged between 50 and 69 years have reported that they received a mammogram within the last two years, revealing the stark reality of early diagnosis [4]. The total examination coverage ranged from 49% (East), 62% (West), 64% (North) to 69% (South) [5]. In fact, most countries retain a screening rate that is less than 50%, such as the Slovak Republic in which only 20% of women aged between 50 and 69 are screened annually [6]. Romania had the lowest proportion of eligible women screened for breast cancer in 2010 (13%), thereby facing an increase in breast cancer mortality [6]. In contrast, Poland faced a drastic increase in screening with an uptake of 45%, however, Poland continued to report increased mortality rates. This discrepancy can be attributed to the exclusion of Polish women between the ages of 40-49 and 70-74 in breast cancer screening programs [7]. Similarly, Estonia has faced a screening uptake from 41% to 58% since expanding its screening programs from women between the ages of 45-59 with healthcare coverage to all women between the ages of 50-65 [7]. These scenarios explicate the strong positive correlation between screening and mortality rates in European countries. Annually, 21,680 breast cancer deaths have already been averted as a result of breast cancer screening [8]. In researching the reason for under participation in mammography screening, we have recognized that a multitude of factors such as physician quality, education, and marital status play an influential role. Overall, 81.6% of married participants underwent breast cancer screening relative to 74.2% for divorced/widowed/separated individuals, and 74.7% for never-married individuals [9]. This could be attributed to the fact that screening guidelines strongly recommend women of older age to be screened periodically in healthcare facilities.

European guidelines do not recommend any extra screening for women with dense breasts, however, women between the ages of 45 and 74 who are asymptomatic and have dense breasts are strongly suggested to have a digital breast tomosynthesis [10]. Furthermore, European countries require two different radiologists to interpret the mammograms, lowering the false-positive rate by a factor of two or three in comparison to the US [11]. Although guidelines have been established to address the early diagnosis, there is potential for more efforts to bridge the diagnosis gap in Europe. There is also a stark difference in screening rates between urban and rural populations within Europe. According to the Norwegian Breast Cancer Screening Program, Oslo (capital of Norway) had a lower attendance rate (90% vs. 79%) than rural locations, which most likely reflected varied availability to private mammography services [30]. Overdiagnosis and false-positive mammography in scheduled mammography screening may have an impact on screening participation [30].

Created by Rakshita Raajesh and Tushita Bordoloi © Breast Cancer Hub. Data source: [12]. The graph indicates that certain countries possess a screening rate under 25% which is highly dangerous and may be attributable to local regulations, location, and social opinions.

Key Risk Factors

Due to the rise of a fast-paced lifestyle heavily centered around Western ideals and societal pressures, individuals are commonly indulging in practices that expose them to risk factors. The evolution of diets is another contributor to the rising number of breast cancer cases. According to a meta-analysis research, women who consume the most total fat had a 13% greater chance of developing breast cancer than those who consume the least total fat [13]. Based on fatty acid intake data from 24 European countries, mean intakes ranged from 28.5 to 46.2% of total energy (%E) for total fat, from 8.9 to 15.5%E for SFA (saturated fatty acid), from 3.9 to 11.3%E for PUFA (polyunsaturated fatty acids) [14]. These statistics show that SFA intakes were above the recommended range and PUFA intakes which are considered healthy were below the recommended range. The mean intake of SFA was highest in Greece with an average breast cancer mortality rate of 33.7% and the lowest in Portugal where the mortality rate is 28.0% [15]. This subtle but significant difference in mortality rates between the two countries illustrates the role diet, specifically fat intake, can play in the development of breast cancer.

Similarly, according to an EPIC investigation, both high and moderate levels of physical activity, including both leisure and domestic chores, were independently linked to a lower risk of developing premenopausal and postmenopausal breast cancer. In fact, 9% of breast cancer cases in Europe are because of inadequate physical activity [16]. A poor diet and inadequate physical activity can contribute to obesity which has also been shown to directly correlate with increased breast cancer incidence. Studies have established that weight gain in middle adulthood (women aged 40–50 years) increased the risk of breast cancer and each 5kg gained increased the risk of breast cancer among postmenopausal women [16]. This heightened risk can be attributed to the increased production of estrogen in fat tissue. Our meta-analysis of the effects of diet and physical activity has brought us to the conclusion that deficient diet and physical activity standards can lead to a higher predisposition for breast cancer.

In Europe in 2018, smoking-related cancer cases accounted for 572,000 male and female cancer cases, or 28% (for males) and 10% (for females), respectively [17]. In fact, alcohol consumption is the highest in Bulgaria and Romania in which mortality rates are 36.2% and 36.3%, respectively, in comparison to an average mortality rate of 34.1% [18]. Alcohol and tobacco consumption have a noticeable impact on breast cancer incidence in the European Union. Alcohol contributes to a surge in estrogen levels, thereby increasing the risk of developing breast cancer since estrogen stimulates the division and proliferation of breast tissue. Breast cancer risk increases by 4.2% for each 10g/day increase in alcohol consumption and continues to increase for larger amounts of consistent alcohol intake [18]. While this is applicable globally, of the 50,000 breast cancer cases caused by alcohol consumption worldwide, 5% are from Europe and North America and 2% are from light drinking [18]. In most European countries, light drinking is associated with a higher proportion of alcohol-attributable cancer cases. This is the case since more Europeans drink in this manner and therefore, more cases arise from this category. In Germany, most women with breast cancer cases that are attributable to alcohol consumption drink less than 45 grams of alcohol, which is equal to four drinks [19]. Alcohol consumption is extremely high in Europe which is precedented due to the large-scale production of alcohol in Europe. Western Europe is accountable for most sales of alcohol with a market value of 359 billion euros, resulting in an increased incidence of breast cancer cases [19].

Similarly, the use of tobacco can contribute to the introduction of carcinogens that could cause DNA damage and contribute to the irregular formation of epithelial cells. Tobacco use is highest in Bulgaria, Greece, and Latvia [20] which also have above-average mortality rates of 36.3%, 33.7%, and 43.6%, respectively. These countries consume high amounts of tobacco given the fact that these countries and Italy, Spain, Poland, Croatia, and France account for 99% of tobacco production. Most of these countries are to the west which indicates a correlation between tobacco consumption and breast cancer incidence due to high incidence rates in Western Europe. Moreover, European retailers do not require a government-authorized license to sell tobacco products which can lead to a lack of point-of-sale tobacco control policies and denormalization of tobacco, making it very easy for Europeans to access and rely on tobacco. Easy access to alcohol and tobacco has increased the precedence of breast cancer cases in Europe and has increased the ability of Europeans to acquire these substances.

The increased number of breast cancer cases in Europe can also be attributed to the presence of mutated genes 1 and 2 (BRCA1 and BRCA2), tumor suppressor genes that repair damaged DNA, which are associated with a higher risk of developing breast cancer. The presence of BRCA1 or BRCA2 is a threat to Europeans: most people of Ashkenazi Jewish, Dutch, French Canadian, Icelandic, and Norwegian descent [21]. While people with BRCA1 or BRCA2 mutations constitute 0.2% of the global population, the mentioned populations have reported an incidence rate that is ten times larger -  2.6% of the population [21]. Unfortunately, men and women who have inherited the BRCA1 and BRCA2 gene may pass the gene to their children, who then have a 50% chance of inheriting the variant. People who have inherited the variant have an increased risk of expressing the gene, in turn, indicating a higher susceptibility to developing breast cancer. 55%–72% of women who inherit a harmful BRCA1 variant and 45%–69% of women who inherit a harmful BRCA2 variant will develop breast cancer by 70–80 years of age [22].

Breast cancer incidence increases with the increased use of contraceptive pills and hormone replacement therapy. A study conducted by the PRAC (EU Pharmacovigilance Risk Assessment Committee) demonstrated that, with the exception of vaginally administered estrogen, all forms of menopausal HRT were linked to a higher risk of breast cancer [23]. In a survey of 8012 European women between the ages of 45 and 75, 16% of women currently used hormone replacement therapy (HRT) while 16% used to undergo HRT [23]. A quarter of postmenopausal women claimed to have used HRT at some point. By nation, the percentage of perimenopausal women receiving HRT varied from 18% in Spain to 55% in France [23]. Although Europe is known for using HRT less frequently than the US, the UK and Scandinavian countries have been reported to resort to HRT. In fact, European women will have access to cheaper hormone replacement therapy from April 1st, 2023 [23].

Occupational experiences can contribute to the development of breast cancer and higher mortality rates. People who are required to work night shifts have a higher risk of developing breast cancer since exposure to artificial light contributes to lower melatonin levels and melatonin is known for reducing the circulation of estrogen and inhibiting tumor growth. In a 34-year overview of night work in France, data uncovered that approximately 19-25% of Europeans in France work night shifts and there was a 97% increase in night work for women [24]. Some occupational experiences include hazardous environments which can contribute to the exposure of noxious chemicals. One such chemical called ethylene oxide has been identified by the International Agency for Research on Cancer as a cause of cancer development. In fact, Swedish sterilant workers exposed to concerning amounts of ethylene oxide are 2-3 more likely to develop breast cancer than those exposed to meager amounts according to a cohort study [24]. In fact, using ethylene oxide as a pesticide for the fumigation of foods and food storage areas has been banned by the EU due to the toxic nature of the chemical.

15% of breast cancer cases in Europe are classified as triple-negative breast cancer (TNBC) [25]. TNBC is a type of cancer where cancer cells are missing progesterone receptors, estrogen receptors, and produce little to no HER2. TNBC grows rapidly, possessing the possibility of becoming multidrug-resistant, and is highly likely to reemerge upon treatment [25].

Demographic/ Regional Factors

All EU-28 are considered developed countries and it has been observed that developed countries show a higher incidence of breast cancer. The Western lifestyle which includes unhealthy diets like fast food, which leads to obesity, and also the consumption of alcohol and tobacco, is a big reason why the incidence rate is so high. Though the incidence rate is higher in developed countries, like the EU-28 countries, the mortality is also lower compared to developing countries. The 1-year survival rate of breast cancer in European countries varies from 94.1% in Scotland to 97.1% in Italy [26]. Because of the delay in seeking diagnosis of and treatment for breast cancer in developing countries, the survival rate is lower [26]. It is challenging to gather information regarding genetic disposition since access to genetic counseling and testing differ across countries, however, population-based studies have found a prevalence of mutations (BRCA1 and BRCA2) in 0.2% in the general population, 1.6% in Inuits, 0.4% in Icelanders, and up to 2.5% in the Ashkenazi Jewish population [27]. Geographic clustering of two recurrent BRCA1 mutations in France's north-eastern region is obvious, pointing to a founder impact [27]. It was also found that ER(estrogen receptor)-negative breast cancer was correlated with breast cancer risk in BRCA1 mutation carriers.

With an area of four million miles and a population of 746.4 million, Europe is geographically divided into four subregions: northern, southern, western, and eastern/central. Beyond the physical differences between each subregion, there are noticeable disparities in the stigmatization and treatment of breast cancer. North and Western European countries have a higher number of reported breast cancer cases and higher survival rates, while Eastern European countries have lower survival rates. The average 5-year survival rate was 73%, but it ranged from 58-60% in Eastern Europe (Poland, Estonia and Slovakia) to 77-81% in Northern and Western Europe (Sweden, Finland, Iceland, Switzerland, France and Italy). Denmark (86%), the UK (86%), and Ireland (82%) are the other northern nations where survival rates are comparable to those in Western Europe [25]. Eastern European countries have a noticeably lower survival rate due to a lower GDP which indicates that these countries are less developed than countries with previous democratic systems such as those to the west. Having a lower GDP, these countries are faced with the challenge of maintaining high standards for healthcare services and facilities.

Created by Rakshita Raajesh and Tushita Bordoloi © Breast Cancer Hub. Data source: Dafni, U., Tsourti, Z., & Alatsathianos, I. (2019). Breast Cancer Statistics in the European Union: Incidence and Survival across European Countries. Breast Care, 14, 344 - 353 [1].

The graph indicates that breast cancer incidence is highest in Northern and Western Europe as claimed.  However, the survival rates are low for these respective areas which can be attributed to economic disparities and lack of accessibility to healthcare services.

Environmental Factors

Europe has been affected the most by climate change due to extreme heat, droughts, and wildfires. The temperature in Europe in 2022 was around 2.3 °C higher than the pre-industrial average (1850–1900), which served as the basis for the Paris Agreement on climate change [28]. The warmest year on record was experienced by a number of nations, including Belgium, France, Germany, Ireland, Italy, Luxembourg, Portugal, Spain, Switzerland, and the United Kingdom [28]. Increased temperatures mitigate the ability of our bodies to fight persistent diseases and intensify the effect of toxic chemicals and pesticides. The direct effects of extreme temperatures like heat waves may worsen the conditions of cancer patients because of their impaired thermoregulation and immune function [29].

Conclusion

Through the analysis of the influence of demographic, socioeconomic, and regional factors on breast cancer incidence in Europe, we have uncovered how the disparities within these factors contribute to higher incidence and mortality rates in Europe. In conjunction with these disparities, differences in diagnostic services and treatment plans contribute to the widening gap of accessibility to healthcare services and facilities. Our study has explicated these differences and identified potential causes for the poor healthcare services and treatments.

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