Social epidemiology of female breast cancer in the region of Varna-Bulgaria in 2013-2021 – A retrospective study (original) (raw)

Introduction

During the last several years, breast cancer has been the most common malignant disease and a leading cause of death in women worldwide and in Bulgaria as well. In 2020, approximately 2,300,000 new breast cancer cases and 685,000 deaths in women were registered worldwide.1 Breast cancer continues to be the most common cancer globally, affecting 7.8 million males and females at the end of 2020.

The analysis of data on breast cancer outcomes obtained from the 2019 Global Burden of Disease Survey during the period between 1990 and 2019 in five big countries such as Brazil, Russia, India, China, South Africa as well as in 30 other Asian countries demonstrates that in 2019, there are 900,000 female breast cancer cases and 350,000 million deaths in these parts of the world.2 China and India have the largest proportion of incident cases and deaths followed by Pakistan. High body mass index, high fasting plasma glucose, and a diet high in red meat contribute to the highest breast cancer death rates in most of these countries in 2019.

In 2019, there were 19,726 breast cancer deaths in the nine Central and Eastern Europe countries: Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia.3 These breast cancer deaths result in 267,184 years of life lost. The mean present value of future lost productivity in these countries is the following: €85 M in Poland, €46 M in Romania, €39 M in Hungary, €21 M in Slovakia, €18 M in Serbia, €16 M in Czech Republic, €15 M in Bulgaria, €13 M in Croatia, and €7 M in Slovenia. In 2019 alone, lost productivity costs due to premature breast cancer-related mortality exceed €259 million.

The investigation of breast cancer burden in 28 European Union member states demonstrates age-standardized (world standard) incidence and mortality rates in adolescents and young adults aged 15-39 years in 2020 of 20.1 per 100,000 and 2.70 per 100,000, respectively, in Bulgaria only.4 The age-adjusted mortality rate in Poland is 2.70 per 100,000, too. It is highest in Iceland (of 2.80 per 100,000) and lowest in Luxembourg (of 0,66 per 100,000) against a mean value in Europe of 1.94 per 100,000.

The aim of this study was to follow up on the annual dynamics of the incidence, prevalence and mortality rates of female breast cancer in the region of Varna, Bulgaria, in the period from 2013 to 2021.

Methods

Analysed data

We conducted a retrospective analysis of the statistical data devoted to the crude incidence, prevalence and mortality rates of breast cancer in women living in the region of Varna from the information system of Marko Markov Specialized Hospital for Oncological Diseases of Varna for 2017-2021. Study cohort includes 1341 diagnosed patients aged between 24 and 95 years, distributed by years and age. The information about the age-standardized incidence and prevalence rates from two most recent official Bulgarian publications5,6 for 2013-2017 was also analysed.

Statistical analyses

The graphical presentation and statistical analyses were performed using, GraphPad Prism V.6 (San Diego, CA, USA). GraphPad Prism software is accessible online from https://www.graphpad.com/features.

Results

The total number of newly registered cases of breast cancer in women aged between 24 and 95 years stands at 1,341 (Table 1). The incidence rate gradually decreases during the period from 2017 to 2021.

Table 1. Annual dynamics of new breast cancer women according to age groups in the region of Varna.

As shown in Table 1, the age group between 61 and 70 years is most frequently affected during the whole period (356 patients or 26.55% of the cases). There are eight young women, too (0.5% of the cases).

The mean breast cancer crude incidence rate per 100,000 population decreases from 2017 to 2021 while mean breast cancer crude prevalence rate per 100,000 population varies considerably during this period (Table 2).

Table 2. Annual dynamics of the mean breast cancer crude incidence and prevalence rates per 100 000 population in the Region of Varna.

The annual dynamics of the newly registered cases and of the death cases by year of diagnosis in the region of Varna during the period between 2013 and 2021 are illustrated in Figure 1 and Figure 2, respectively.

Figure 1. Annual dynamics of newly registered cases by year of diagnosis in the Region of Varna.

Figure 2. Annual dynamics of deaths by year of diagnosis in the Region of Varna.

The annual dynamics of the newly registered cases by year of diagnosis of female inhabitants in the city of Varna only during the period between 2017 and 2021 are displayed in Figure 3.

Figure 3. Annual dynamics of new cases by year of diagnosis of female inhabitants in the city of Varna only.

The annual dynamics of the mean breast cancer age-standardized incidence and prevalence rates per 100,000 population in the region of Varna between 2013 and 2017 are presented in Table 3.

Table 3. Annual dynamics of the mean breast cancer age-standardized incidence and prevalence rates per 100 000 population in the Region of Varna.

The total number of deaths until the end of 2022 amounts to 310 being the greatest 2018 (81 or 30.22%) and in 2017 (79 or 27.24% of the cases). We observed that since 2019 lethal cases are gradually reduced (Figure 4).

Figure 4. Annual dynamics of deaths by year of diagnosis after radical surgery in the Region of Varna.

In 2017-2021, bilateral breast cancer is diagnosed in twenty-four women. The malignant neoplasm is synchronous in fifteen and metachronous in the rest nine patients. Of them, three women with a synchronous and one woman with a metachronous breast cancer decease.

In 2013 and 2014, breast cancer age-adjusted incidence and mortality rates are much higher in the region of Varna than those in five other regions in North Eastern Bulgaria such as Ruse, Shumen, Dobrich, Razgrad, and Silistra.7

Discussion

There is a dramatic reduction of the number of lethal cases following the radical surgical intervention since 2019 proving the effectiveness of the timely application of this method of treatment (Figure 4). Our findings are similar to these recently reported by foreign authors.

During the period between 2004 and 2018, 915,417 new breast cancer cases are diagnosed in the USA.8 Among all races, there is an increased incidence rate by 0.3% (between 0.1% and 0.4% at 95% confidence interval; p<0.001) per year during the study. There is a decreased mortality rate by 14.3% (between 18.1% and 10.4% at 95% confidence interval; p<0.001). This reduction is most outlined from 2016 to 2018 by 48.6% (between 52.6% and 44.3% at 95% confidence interval; p<0.001). The analysis of 1999 to 2020 overall mortality rate due to female breast cancer in the USA according to data from the Centres for Disease Control and Prevention and the National Centre for Health Statistics indicates that it decreases and varies by race/ethnicity, age group, and US Census region.9 Its largest decrease is observed among non-Hispanic white women, women aged between 45 and 64 years, and women living in the Northeast, while its smallest decrease is established among non-Hispanic Asian or Pacific Islander women, women aged 65 years or older, and women living in the South.

Within an inquiry study through a food frequency questionnaire of 6,157 North American women diagnosed with invasive breast cancer between 1993 and 2011 and followed-up through 2018 during a median time of 11.3 years, there are 1,265 deaths.10 Women in the highest versus lowest quartile of adherence to the following four diet quality indices have a lower risk of all-cause mortality: the Healthy Eating Index-2015, Alternative Healthy Eating Index, Alternative Mediterranean Diet, and Dietary Approaches to Stop Hypertension. The values of multivariable-adjusted hazard ratios in terms of these indices are the following: 0.88 (between 0.74 and 1.4 at 95% at 95% confidence interval), 0.82 (between 0.69 and 0.97 at 95% confidence interval), 0.73 (between 0.59 and 0.92 at 95% confidence interval), and 0.78 (between 0.65 and 0.94 at 95% confidence interval).

In 2023, 297,790 newly registered breast cancer cases are projected to occur in the United States of America.11 The total number of these cases will reach up to 31% of the patients with ten most common malignant diseases. Besides the total number of death, cases due to breast cancer will reach up to 43,170 or to 15% of the patients with ten most common malignant diseases.

Between 2014 and 2019, 55,465 breast cancer patients at a mean age of 55.7±12.0 years (range, 25 to 97 years) are diagnosed in Kazakhstan based on nationwide large-scale healthcare data from the National Registry.12 Most patients (44.8% of the cases) are aged between 45 and 59 years. Incidence rate varies between 45 per 100,000 population in 2015 and 73 per 100,000 population in 2016 while prevalence rate increases from 304 per 100,000 population in 2014 up to 506 per 100 000 population in 2019. Mortality rates are stable and high in the senile patients aged between 75 and 89 years. Mortality is positively associated with diabetes mellitus (hazard ratio of 1.2; between 1.1% and 2.3 at 95% confidence interval) and negatively associated with arterial hypertension (hazard ratio of 0.42; between 0.4% and 0.5% at 95% confidence interval).

Based on data on breast cancer incidence rate between 1999 and 2020 and breast cancer mortality rate between 1993 and 2021 in South Korea, the results from their projection by fitting a linear regression model indicate that in 2023, there will be 28,851 new cases (22.4% of ten most common malignant diseases) and 2,944 death cases (9.2% of these diseases).13 Crude and age-adjusted (world standard) incidence rates of 111.9 per 100,000 population and 67.7 per 100,000 population as well as crude and age-adjusted (world standard) mortality rates of 11.4 per 100,000 population and 5.7 per 100,000 population, respectively, could be expected.

Within a hospital-based retrospective cohort study in South Ethiopia, 302 female breast cancer patients diagnosed from 2013 to 2018 are followed-up for a total of 4685.62 person-months.14 Their median survival time is 50.81 months. About 83.4% of them have advanced-stage disease at presentation. The overall survival probability at two and three years is 73.2% and 63.0%, respectively. Independent predictors of mortality are the following: patients residing in rural areas (adjusted hazard ratio of 2.71; between 1.44 and 5.09 at 95% confidence interval), travel time to a health facility ≥7 hours (adjusted hazard ratio of 3.42; between 1.05 and 11.10 at 95% confidence interval), patients presenting within 7-23 months after the onset of symptoms (adjusted hazard ratio of 2.63; between 1.22 and 5.64 at 95% confidence interval), patients presenting more than 23 months after the onset of symptoms (adjusted hazard ratio of 2.37; between 1.00 and 5.59 at 95% confidence interval), advanced stage at presentation (adjusted hazard ratio of 3.01; between 1.05 and 8.59 at 95% confidence interval), and patients having never received chemotherapy (adjusted hazard ratio of 6.69; between 2.20 and 20.30 at 95% confidence interval).

During the period from 1999 to 2020, breast cancer mortality rate in South Africa increases from 9.82 per 100,000 to 13.27 per 100,000 at around of 1.4% per annum (between 0.8% and 2.0% at 95% confidence interval; p<0.001).15 Young women aged 30-49 years present with a statistically significant mortality rate increase (by 1.1%-1.8%; p<0.001).

Between 2009 and 2016, 10,124 deaths from breast cancer are recorded in the Mortality Information System in the city of São Paulo, Brazil, among women aged 20 years and over.16 The following variables are associated with breast cancer mortality: travel time between one and two hours to work (relative risk of 0.97; between 0.93 and 1.00 at 95% credible interval), women being the head of the household (relative risk of 0.97; between 0.94 and 0.99 at 95% credible interval), and deaths from breast cancer in private health institutions (relative risk of 1.04; between 1.00 and 1.07 at 95% credible interval). During the period from 1999 to 2019, there are stable temporal trends of overall mortality coefficients for breast cancer (β=-0.006; between -0.02 and 0.01 at 95% confidence interval) in Passo Fundo, Rio Grande do Sul, Brazil.17 A rising mortality trend is identified in women with up to 7 years of schooling and in older women as well.

The analysis of data from the Polish National Cancer Registry shows that between 2000 and 2019, a total of 315,278 patients, 2,353 male patients and 312,925 female patients, are diagnosed with breast cancer.18 The age-adjusted five- and ten-year net survival is statistically significantly higher in women than in men (77.33% versus 65.47%; p<0.001). There is a statistically significant increase only in female survival (by 7.32%; p<0.001) between the earliest period (2000-2004) and latest one (2015-2019). The standardized mortality ratios are considerably higher for women than for men (3.35 versus 2.89, respectively).

In 2019, breast cancer age-standardized incidence rate is statistically significantly higher in Sweden (217.5 per 100 000) than in Crete (58.9 per 100,000) (p<0.001).19 During the period between 2005 and 2019, breast cancer age-standardized mortality rate decreases in Sweden from 25.5 per 100,000 down to 16.8 per 100,000 while it increases in Crete from 22.1 per 100,000 up to 25.3 per 100,000. Since 2015, there is a successive rise of survival rate with a five-year survival rate of 92% in Sweden but a decrease of the survival rate with a five-year survival rate of 85% in Crete.

The results from a case-referent investigation of 1,571 women in Flanders, Belgium, during the period between 2005 and 2017 indicate that women who have participated in the Flemish population-based mammography screening program introduced in 2001 have a 51% lower risk of breast cancer-specific mortality compared to those who have not (adjusted odds ratio of 0.49; between 0.44 and 0.55 at 95% confidence interval).20

During the recent years, there are relatively scanty regional epidemiological investigations dealing with breast cancer in women worldwide. It should be emphasized that the significant differences in terms of the dynamics of breast country incidence, prevalence and mortality rates in single regions in Bulgaria and in other European countries deserve a special attention by the public. The research in this interdisciplinary field accomplished by national and international collectives could shed light on a variety of unsolved issues associated not only with environmental and occupational factors but also with personal life-style improvement.

Conclusion

We establish a gradual improvement of the epidemiological parameters of female breast cancer in the region of Varna during the last few years. The performance of regular regional epidemiological research of the most common and socially significant malignant diseases in Bulgaria could contribute to the enhancement not only of the effectiveness and quality of their prevention, but also of their timely diagnosis and adequate complex treatment.

Ethical considerations

Recent retrospective study was approved by the Ethics Committee of Medical University-Varna, Bulgaria (protocol № 61/30.03.2017) on 30th March 2017 and is in accordance with Declaration of Helsinki, 1964.

Due to the retrospective nature of the study, the need for informed consent of the patients was waived by the committee. This study includes epidemiological analyses concerning patients, that are part of a larger previous study in which the ethics committee approved the use of these data. The data and results presented in this study have not been previously published.