Female Breast Cancer Mortality Rates in Turkey

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% (1.38 million) of the total cancer cases (6.038 million) and 14% (458,400 deaths) of the cancer deaths (3.346 million) in 2008. Breast cancer is also the leading cause of cancer death among women in economically developing (268,900 deaths, 12.7% of total) and developed countries (189,500 deaths, 15.5% of total). (Jemal et al., 2011) Breast cancer is also the most common cause of cancer death among women (522,000 deaths in 2012) and the most frequently diagnosed cancer among women in 140 of 184 countries worldwide (Ferlay et al., 2013). Although breast cancer is thought to be a disease of the developed world, almost 50% of breast cancer cases and 58% of deaths occur in less developed countries (Ferlay et al., 2010). Globally, breast cancer incidence and mortality rates among women have been increasing rapidly in many Eastern European, Asian, Latin American, and African countries (Jemal et al., 2010). The lowest breast cancer mortality rates were found in Eastern Asia and Southeastern Asia and Pacific (Jemal et al., 2011). Breast cancer was the leading cancer site in women in all countries of Europe in 2012. The range of mortality rates varies (15-36 per 100,000). Mortality rates were highest in Macedonia, Serbia, Belgium and Denmark, respectively (Ferlay et al., 2013, Ilic et al., 2013). Znaor et al found that in women, breast cancer mortality significantly declined in Slovenia, Croatia and Malta (AAPC -2%, -1% and -5%, respectively), but not elsewhere (Znaor et al., 2013).


Introduction
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% (1.38 million) of the total cancer cases (6.038 million) and 14% (458,400 deaths) of the cancer deaths (3.346 million) in 2008.Breast cancer is also the leading cause of cancer death among women in economically developing (268,900 deaths, 12.7% of total) and developed countries (189,500 deaths, 15.5% of total).(Jemal et al., 2011) Breast cancer is also the most common cause of cancer death among women (522,000 deaths in 2012) and the most frequently diagnosed cancer among women in 140 of 184 countries worldwide (Ferlay et al., 2013).
Although breast cancer is thought to be a disease of the developed world, almost 50% of breast cancer cases and 58% of deaths occur in less developed countries (Ferlay et al., 2010).
Globally, breast cancer incidence and mortality rates among women have been increasing rapidly in many Eastern European, Asian, Latin American, and African countries (Jemal et al., 2010).The lowest breast cancer mortality rates were found in Eastern Asia and Southeastern Asia and Pacific (Jemal et al., 2011).
Breast cancer was the leading cancer site in women in all countries of Europe in 2012.The range of mortality rates varies (15-36 per 100,000).Mortality rates were highest in Macedonia, Serbia, Belgium and Denmark, respectively (Ferlay et al., 2013, Ilic et al., 2013).Znaor et al found that in women, breast cancer mortality significantly declined in Slovenia, Croatia and Malta (AAPC -2%, -1% and -5%, respectively), but not elsewhere (Znaor et al., 2013).

Female Breast Cancer Mortality Rates in Turkey
Nurhan Dogan 1 *, Dilek Toprak 2 In this research we aimed to evaluate temporal changes in mortality rates of female breast cancer in the population of Turkey between the years 1987-2008.

Materials and Methods
The study comprised the female population of the Turkey during the period 1987-2008.Cancer mortality data (provinces and districts) on women who died of breast cancer (codes 174 revision 9 and C50 revision 10 of the International Classification of Diseases (ICD) were obtained from the Turkish Statistical Institute death database (TurkStat, 2013).According to age groups' population distribution of years 1990 and 2000, the provincial and district centers, other years' midyear female population has been obtained.The rates were age-standardized (ASR per 100,000 person-years) using the direct method and the European standard population.

Statistical analysis
Joinpoint regression is a statistical modeling technique that explains the relationship between two variables by means of a segmented linear regression constrained to be continuous everywhere, in particular, in those places where the slope of the regression function changes.This technique is widely applied to the modeling of time trends in mortality or incidence series in epidemiological studies (Miguel et al., 2011).
Trends in age-standardized cancer mortality rates were calculated by joinpoint regression using Joinpoint software version 4.1.0(Natinal Cancer Institutes, 2013).Joinpoint regression was used to detect points (i.e., "joinpoints") where the trends changed significantly.The analysis starts with the minimum number of joinpoints and tests whether one or more joinpoints are statistically significant and must be added to the model.Number of joinpoints were determined by performing permutation tests, each of which had a correct asymptotic significance level.These significance level were found using Monte Carlo methods and applying Bonferroni corrections (Kim et al., 2000).The final model shows (Fit an autocorrelated errors model based on the data), the best fitting joinpoints where the rate changes significantly.Each joinpoint informs of a statistically significant change, an estimated annual percent change (APC) and average annual percent change (AAPC) that are computed along with its 95% confidence intervals (95%CI).AAPC is the geometric mean of the annual changes from all of the partitions.Also AAPC takes into account trend transitions (Clegg et al., 2009).
In this study, each of detected trends were calculated by fitting a regression line to the natural logarithm of the rates, using calendar year as regressor variable [ln(rate)=a+bx], where x is calendar year; APC was estimated as.The APC was considered significant if the confidence interval does not include zero.The parameters were allowed with maximum of four joinpoints to enter the final model while having minimum of 4 years between two joinpoints.The analyses were applied with a significance level of 0.05.
Age standardized death rates per 100,000 people (using European standard population) were calculated for each calendar year using direct standardization the changes in the age-standardized mortality rate over the 22-year period were analyzed for cancer by fitting the joinpoint regression model.Ten-year age groups were used for the standardization.This approach adjusts crude rates according to the age distribution, so it is useful to compare populations of different cities or countries (Ahmad et al., 2001).The subgroup analyses were also performed; the age groups were divided in four strata and were created to approximate premenopause (25-44 years old), perimenopause (45-54 years old), the first ten years of the postmenopausal period (55-64 years old), and thereafter (≥65 years old), respectively.As there were very few breast cancer deaths, the results are not shown for ages <25 years.

Results
Nearly 23,000 breast cancer deaths occured in Turkey during the period 1987-2008, with the average annual agestandardized mortality rate (ASR) being 11.9 per 100,000 women.The standardized, or ASR increased from 9.2 per 100,000 women in 1987 to 14.9 per 100,000 in 2008.Also numerous year-to-year fluctuations in the mortality rate for females due to breast cancer are seen in the Figure 1 and 2.
Trends in breast cancer mortality were calculated using joinpoint regressions analysis.The results of the joinpoint regression analysis (i.e., the points in which the rates are changed significiantly), the APC for each trend and the AAPC for females (according to age-strata) are shown in Table 1.
Female breast cancer mortality is strongly related to age, with the highest mortality rates being in older women.In last 5 years, the most significant increase was in perimenapausal period by 4.3% per year.In the 25-44 years age group, during the 22 years observation period, a steady and significant increase in the mortality of breast cancer rates was observed (Table 1).
Among women 45-54 years old, two joinpoint model  were obtained as the best model.Breast cancer mortality rates presented a significant increase of 6.2% per year from 1987-1994, and a significant decline of 10.4% per year from 1994-1997, followed by a significant increase to the end of period in 1997 (by 4.3 per year).
In older age group (65 years and over), breast cancer mortality rates declined during the period 1987-1990 (by-4.5% per year), but this decline was not statistically significant.In this age groups, a significant increase in breast cancer mortality rates observed during the period 1990-1994 (by+15.7%per year) which was followed by non-significant decrease until 1997 and followed by a non-significant increase at the end of the period.
Compared with the <45 age group, higher rates were observed in the perimenopausal period, and rates were highest in the postmenopausal periods of women's lives (Figure 3).
Mortality rates were higher in the postmenopausal periods (≥55 years).Regarding the Figure 4, we can see the steadily increase of breast Cancer Related Average Mortality Ages by years.Mortality rate is higher in perimenopausal period (45-54 years) than premenopause (<45 years), but in postmenopausal period (≥55years old) the mortality rate is the highest.

Discussion
Breast cancer is treatable and curable cancer type when diagnosed early (Eskiocak and Çatal B, 2005).Today although the increase in its incidence, with screening tests, early and easy diagnosis makes this cancer type more important (Parkin et al., 2005).
The present study demostrated that the average annual age-standardized mortality rate (ASR) is 11.9 per 100,000 women and breast cancer mortality has been increasing during the period 1987-2008 in Turkey.Regarding these mortality rates Turkey is among the countries with low breast cancer mortality rates however, a steady increase was observed through the years.
Considering the results of our study the increase of mortality rates can be defined as parallel to the increase of the population and general increase of breast cancer mortality rates in global world.Also this is partly because a shift in lifestyles.As the time passed, lifstyle of women changed in Turkey.This caused an increase of breast cancer risk factors like relatively late age at first birth, less/no breastfeeding, smoking and alcohol consumption.

Years
According to our study across all age groups, there was a significant increased trend in 45-54 age group (AAPC=2.5, 95%CI= 1.6-3.4),especially in last 5 years (AAPC=4.3,95%CI= 2.6 to 6.0).This would be because of the hormonal factors, using more screening tests and more visit to physicians for menopause or any other complaint in those ages which causes more diagnosis.
Evaluating the age-standardized breast cancer mortality rates by years we can say that mortality rates especially increase in older ages.This may be as a result of new treatment methods and long life of women diagnosed as breast cancer.
Breast cancer mortality rates vary among countries and there are huge inequalities between rich and poor countries.For example it is the commonest incident form of cancer in African region.In women, cervix cancer and breast cancer were the commonest incident and fatal forms of cancer by a considerable margin in WHO South East Asia Region.Regional patterns in mortality rates are generally similar to the incidence patterns, although breast cancer is also a leading cause of cancer death in the less developed countries of the world.Incidence rates remain highest in more developed regions (Switzerland, U.S. whites, Italy, and many other European countries), but mortality is relatively much higher in less developed countries probably due to a lack of early detection and access to treatment facilities.For example, in western Europe, breast cancer incidence has reached more than 90 new cases per 100,000 women annually, compared with 30 per 100,000 in eastern Africa.In contrast, breast cancer mortality rates in these two regions are almost identical, at about 15 per 100 000, which clearly points to a later diagnosis and much poorer survival in eastern Africa.(IARC, 2008).
In our study the mortality rate is 1.6 fold in 20 years.This result should alert us for early diagnose and treatment.The most effective way of early detection is "education"; which is for physicians and also public education.By this way avareness can be raised.
About 60% of the deaths are estimated to occur in economically developing countries.In contrast, breast cancer death rates have been decreasing in North America and several European countries over the past 25 years, largely as a result of early detection through mammography and improved treatment (Althuis et al., 2005;Ravdin et al., 2007;Jemal et al., 2010).In many African and Asian countries however, (Uganda, South Korea, India), incidence and mortality rates have been rising (Choi et al., 2005;Parkin, 2005;2010).
Increases in breast cancer awareness and screening activity may be responsible for the rising incidence in these populations.Maintaining a healthy body weight, increasing physical activity, and minimizing alcohol intake are the best available strategies to reduce the risk of developing breast cancer (Kushi et al., 2006).The relationship between alcohol consumption and breast cancer mortality and recurrence seems to be a doseresponse.Gou et al found that only alcohol consumption of >20 g/d was associated with increased breast cancer mortality, but not with increased breast cancer recurrence (Gou et al., 2013).The breast cancer incidence increases observed in many Western countries in the late 1980s and 1990s likely result from changes in reproductive factors as well as an increased screening intensity.Incidence rates in some of counties, sharply decreased from the beginning of the millennium, partly due to lower use of combined postmenopausal hormone therapy (Ravdin et al., 2007;Canfell et al., 2008;Seradour et al., 2009;Edwardset al., 2010).The factors that contribute to the international variation in incidence rates largely stem from differences in reproductive and hormonal factors and the availability of early detection services.
Comparing with the other country results Turkey has low mortality rate.This could be related with record problems or low risk factors of our women population like long period of breastfeeding in rural areas, limited use of hormone therapy, low alcohol consuption, high consuption of fruits and vegetable.On the other hand inrease of breast cancer mortality rates should alert us for the prevention projects.
Early detection through mammography has been shown to increase treatment options and save lives (Anderson et al., 2006).Recommended early detection strategies in include the promotion of awareness of early signs and symptoms and screening (Anderson et al., 2008).However the USPSTF recommends against routine screening mammography in women aged 40 to 49 years.The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take into account patient context, including the patient's values regarding specific benefits and harms.(Grade C recommendation) The USPSTF recommends biennial screening mammography for women between the ages of 50 and 74 years (Grade B recommendation) and not to screen women 75 years or older.(I statement) (Calonge et al., 2009).
One of the aims of breast cancer programs should be to protect the young age and prevent them from the risks of breast cancer mentioned in

FigureFigure 2 .
Figure 1.Age-Standardized Breast Cancer Mortality Rates by Years

Figure
Figure 3. Mortality Rates Per 100,000 Women for Breast Cancer in Turkey by Years

Table 2 .
In this context, Turkish Ministery of Health and the European Union MEDA programme, carried out a new Project and Cancer Early Diagnosis, Screening And Training Center (KETEM) was established in 2006.In 2009, 122 KETEM centers were giving service for screening, diagnosis, treatment and awareness of cancer and public education in order to reduce the morbidity and mortality rates of cancer (KETEM).The results and success of these centers would