Discussion
Breast cancer continues to be the primary cause of cancer morbidity and mortality among women. Significant variation is observed in breast cancer survival rates from one geographic area to another (Jemal et al., 2010, Curado, 2011). Interestingly, while the Middle East, along with sub-Saharan Africa and Asian countries have the lowest rates of breast cancer in the world, the incidence has been rapidly increasing over the last twenty years, as it has been with other cancers (Amoori et al., 2014). Some of the factors that play a role in early detection include improved screening practices and education (Curado, 2011). .In Iraq, as well as most other Middle East countries, breast cancer predominates as the most frequent cancer among women and continues to steadily increase.
The series of studies presented here sought out to examine different epidemiological profiles with respect to risk factors in Iraq for breast cancer. Established risk factors such as age, family history, and race cannot account for all attributable risk. Other lifestyle choices including alcohol intake, whether the subject smokes, is physically active, and maintains a healthy body weight are also important determinants for the risk of breast cancer in a given population. In addition to this, a number of reproductive risk factors may increase the risk of breast cancer, such as an individual’s age at menarche, whether or not a woman has had an abortion, underwent menopause, at what arg she gave birth to her first child and whether or not she breast fed her children are factors for determining breast cancer risk.
The first study presented in this report investigated the association between various sociodemographic factors, such as age, residence, marital status, level of education, type of work, job nature, and income with the risk of breast cancer. The study sample was approximately the same age (47 years) for both breast cancer cases and non breast cancer controls. Lower incidents of breast cancer were found in older patients, ages 60- 76. The results indicated that women living in rural settings were far more likely (6 times) to get breast cancer than women who lived in urban settings. The percentage of cancer cases increased in unmarried women from 6.0 % in the Control group to 11.3% in the Cases group, indicating that the risk of breast cancer was higher among single women compared to married women. The role of education also played a significant effect on the number of breast cancer cases. The less educated a woman was, the higher the risk for breast cancer. For example, the highest incidence of cancer was determined to be for women who were illiterate (27.3%), and the lowest was found for women who had university educations (6.7%). Furthermore, the rate of BC was 70% for women who were not in the workforce, compared to 30% for working women. Along the same lines, women who had the occupation of housewife had the highest risks of cancer, as compared to women who were retired or self-employed. It is interesting to note that women who worked for the government also had high (23.3%) levels of BC. The reasons for this are unclear, but may be linked to the availability of breast screening programs. In terms of income, the women who had a sufficient income had the lowest incidence of BC (10.7%), whereas the women who had just sufficient or insufficient income levels (48.7% and 40.7%, respectively), had higher levels of BC. These results can be due to a number of complex factors, including health awareness and education as well as lack of access to medical infrastructure.
The role of family history and habits on the risk of breast cancer was also examined. Seventy seven point three percent of BC cases interviewed disclosed that they had no family history of breast cancer (77.3%), whereas those with family history had a BC incidence of only 22.3%. These results suggest that the influence of family history is relatively small. Of those who had a family history, the highest percentage were those who had sisters with BC (52.9%), suggesting that this is the best determinant for predicting the potential of breast cancer in girls. Almost 30% had mothers with breast cancer, and the lowest risk group had aunts with breast cancer. These numbers were comparable to the control groups, however, indicating that a family history has an indirect role to play at best. The incidence of patients who smoked increased the risk of breast cancer from 1.3% in the Control group to 6.0% in the Case group. Therefore, cigarette smoking appears to play an antagonistic role in acquiring breast cancer. A high proportion of BC cases was found in the 1-10 cigarette range. It is possible that other smoking related diseases have a greater impact than BC for those who were heavy smokers (11-20 cigarettes a day). The majority of cases had been smoking for 1 year (44.4%). The results of the family history and habits section of this study indicated that while family history had a small effect on the risk of breast cancer, the effect of smoking was quite large.
No difference was found between the Control and Case groups with respect to age of menarche (Table 3). However, women who had three or more children were more likely to get breast cancer than those who had fewer children (26.3% vs 73.7%, respectively). There was also an increase in the risk of breast cancer for those who had abortions (21.3% in the control group vs 45.1% in the case group). These results suggest that the incidence of breast cancer may be linked to hormonal changes that take place during early stages of pregnancy. No significant differences were observed in the risk of breast cancer and the number of live births that a woman had managed. Interestingly, differences between the age at which the woman gave birth suggested that women between the ages of 20 and 25 years of age had a lower risk of BC than women who gave birth at an early age (<20 years old) or who were older (>30 years old) (Table 4). These results suggest that women with a lower risk of birth problems also had a lower risk of breast cancer. Women who were relatively old to give birth had a risk 3 times higher than these women of acquiring breast cancer (15.1 vs 5.1, respectively).
With respect to menopause, menopausal women had 3.9 times higher risk to acquire breast cancer compared to non menopausal women. Moreover, more than two third of cases (67.6%) were menopausal at age 40 years or less compared to only one third of the controls (32.9%) (Table 5). The results of this study would imply that hormonal changes that take place after a woman’s reproductive life play a significant role in increasing the risk for breast cancer. Moreover, in terms of breastfeeding, it became quite clear that women who did not breastfeed had a much higher incidence of breast cancer than those who did breastfeed (15.0% vs 7.1%, respectively) (Table 6). The incidence of BC dropped significantly when two or more children were breastfed (17% for two, 12% for one, respectively), but did not lower again when 3rd, 4th or 5th babies were breastfed. The link between breastfeeding and cancer has been studied extensively in Western, industrialized countries. It is possible that since breastfeeding disrupts the menstrual cycle, hormonal increases are also disrupted and therefore the likelihood of having breast cancer could in fact be lowered. Again, this is an interesting area of study that requires further exploration. Finding a link between the hormonal environment during breastfeeding as a protective measure against breast cancer could have enormous implications for many women who are at risk. It is also interesting that while breastfeeding more than one child is beneficial to lowering the risk of breast cancer, having three, four or even five children has no additive effect. One explanation could be that the length of time provided to breastfeed two children is sufficient to elicit a physiological change that enables a protective effect against breast cancer. It is also interesting to note that women in the middle East breastfeed their infants for a longer time period than Western women. This fact has not been addressed in this study and would be useful to investigate.
Furthermore, there was no statistical significant difference between Cases and Controls regarding oral contraceptives. Women who were over 30 years of age who used an oral contraceptive were 4.3 times more likely to have breast cancer when compared to women taking oral contraceptives who were under 25 years of age (Table 8). Those who used oral contraceptives for less than a year had a much greater risk of breast cancer than those who had taken oral contraceptives for a year or more. In fact, those who took oral contraceptives for more than a year seemed to have a decrease in the incidence of breast cancer, suggesting that the hormones involved in oral contraceptives had a protective effect against breast cancer. Finally, women who had their ovaries removed had a reduced risk of breast cancer. All of the data collected in the study that investigates oral contraceptives as a variable strongly suggests that there is a significant link between hormonal changes that are involved in the reproductive cycle of women and the increased risk of breast cancer. According to the National Cancer Institute (NCI), the current use of oral contraceptives seems to increase by a small amount the risk of breast cancer. This trend was observed in younger women in particular. The NCI states that this increased risk is removed and goes back to normal ten years after oral contraceptives are discontinued. There is also an increased risk of cervical cancer that is associated with the use of oral contraceptives, although this may be the result of increased sexual activity, and thus an increased risk for human papillomavirus infection, which is largely responsible for cervical cancer. It is interesting to note that conversely, women who use oral contraceptives have reduced risks of ovarian cancer, indicating that there is a protective effect of oral contraceptives.
Oral contraceptives consist of manmade versions of the hormones estrogen and progesterone. Since these naturally occurring hormones can influence the growth of some cancers, much effort has been made to determine the risk of taking the artificial versions of these as birth control pills. This has proven to be a difficult task, because the results of clinical trials have not always been consistent (Burkman et al., 2004). One theory which explains the increased risk of breast cancer concerns the exposure of breast tissue to high levels of hormones for longer periods of time than would take place naturally. It is interesting to note that breast cancer diagnosed in women who had ceased to use oral contraceptives for ten years or more were less advanced than breast cancers that were diagnosed in women who had never used oral contraceptives in the first place (Collaborative group, 1996) Clearly, further studies are required to elucidate the link between oral contraceptives, natural hormonal balances in women’s reproductive life cycles and the development of breast cancer.
With respect to chronic disease, in certain instances, there was a mixture of increased risks for breast cancer. For example, the highest incidence of breast cancer was found for women who experienced hypertension as a chronic illness (at a rate of 18%) (Table 9). In addition to this, for women who had both hypertension and diabetes, the incidence of breast cancer was greater (17.3% vs 6.7% for controls, respectively). Women who were prone to diabetes experienced only a 4% risk of having breast cancer, compared to an 8% risk for the Control group. Furthermore, women who experienced cardiovascular disease had a risk of breast cancer (0.7%) that was lower than other chronic diseases yet greater than the Control group, as did women who had both cardiovascular disease and hypertension. The conclusions that can be drawn from this experiment are difficult to explain at best. It is interesting that hypertension appears to have such a significant effect on increasing the risk of breast cancer. One possible explanation would be that both conditions have a common medical basis, either by genotype, environment or lifestyle, that results in both being presented together in an individual. Clearly, further studies would be essential to further investigate the link between breast cancer and other chronic illnesses such as hypertension.
Examination of body mass index led to the observation that women who were obese had a much higher incidence (29.1 times) of breast cancer than the Control group (Table 10). Differences between the Case group and Control group were far less remarkable for women of a healthy weight or who were somewhat overweight. In this case. The risk of obese women for breast cancer is 16% compared to 0.7% for the Control group of women. The link between obesity and breast cancer is in accordance with the results obtained in Western countries. Again ,the reason behind this link is currently unclear, and further studies are required to elucidate the cause.
Conclusion
In this study, all of the factors that could play a role in the risk of developing breast cancer were analyzed to build multiple logistic regression analysis models. The variables included location, education level, socio economic status, family history of breast cancer, health factors and reproductive information. Based upon this model, it was determined that breast feeding was the most prevalent indicator of the risk of breast cancer. The least relevant variable was education. The conclusion, therefore, is that the ability to breastfeed one’s children is one of the best ways to lower one’s risk for breast cancer. This would suggest that hormones which change during the reproductive cycle can play a protective role in fighting breast cancer. An association between estrogen levels and breast cancer has been well documented (Sestak, 2014, Hapangama et al., 2014, Bilal et al., 2014, Su et al., 2014, Santen et al., 2014). It is important that this information is shared with all women of all ages and socioeconomic backgrounds, to help them live healthy lives free of cancer. It should be noted that the mean age for breast cancer in Iraqi women, like that of women of other Middle Eastern countries, is still much younger than their counterparts in industrialized nations (Al-Hashimi and Wang, 2013, 2014). Iraq in particular has been subjected to a great deal of environmental calamity, such as uranium poisoning and other carcinogenic hazards, due to heavy fighting in the Gulf Wars in that region, and that in some areas, the incidence of cancer has increased dramatically (Fathi et al., 2013, Zekri et al., 2010, Othman et al., 2011, Salim et al., 2009, Busby et al., 2009). The reduced age of breast cancer incidence may also be attributed to significant disparities in care in specific populations which are most vulnerable, such as reported delays in diagnosis (Majid et al., 2009). This can be addressed with culturally appropriate and comprehensive health education and outreach programs, as well as with further epidemiological studies to determine why this trend has continued to this day (Saadi et al., 2012, Alwan, 2012). Merely improving population-based registration will help keep tab on existing cancers and trends in disease progression (Habib et al., 2008). It has also been reported in academic studies that a genetic predisposition may explain the earlier incidence of breast cancer in Iraqi women compared to women in Westernized countries (Runnak et al., 2012, Laitman et al., 2012), For example, a study by Hemminki et al., (2011), demonstrated that for many immigrant groups in Sweden, the diagnostic age of breast cancer is earlier (<50 years) than for Swedish natives, suggesting that biology and genetics plays an important role in the variation in the incidence of breast cancer for different populations. A study conducted on Jewish women with early breast cancer and with ancestry from the Iraq/ Iran/ Afghanistan region suggests that it is entirely feasible that specific ethnic groups in Iraq are at increased risk for this disease due to genetic determinants (Weiss-Salz et al., 2007). More research will elucidate the mechanisms involved in early age breast cancer and will assist in providing a more defensive strategy for vulnerable populations such as the women of Iraq (Najjar and Easson, 2010).
References
Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19(8):1893-907.
Curado MP. Breast cancer in the world: incidence and mortality. Salud Publica Mex. 2011;53(5):372-84.
Amoori N, Mirzaei M, Cheraghi M. Incidence of cancers in kuzestan province of Iran: trend from 2004 to 2008. Asian Pac J Cancer Prev. 2014;15(19):8345-9.
Al-Hashimi MM, Wang XJ. Breast cancer in Iraq, incidence trends from 2000-2009. Asian Pac J Cancer Prev. 2014;15(1):281-6.
Al-Hashimi MM, Wang X. Comparing the cancer in Ninawa during three periods (1980-1990, 1991-2000, 2001-2010) using Poisson regression. J Res Med Sci. 2013 Dec;18(12):1026-39.
Fathi RA, Matti LY, Al-Salih HS, Godbold D. Environmental pollution by depleted uranium in Iraq with special reference to Mosul and possible effects on cancer and birth defect rates. incidence rates in most cancer types. Med Confl Surviv. 2013 Jan-Mar;29(1):7-25.
Zekri AR, Bahnassy AA, Mohamed WS, El-Kassem FA, El-Khalidi SJ, Hafez MM, Hassan ZK. Epstein-Barr virus and breast cancer: epidemiological and molecular study on Egyptian and Iraqi women. J Egypt Natl Canc Inst. 2012 Sep;24(3):123-31.
Saadi A, Bond B, Percac-Lima S. Perspectives on preventive health care and barriers to breast cancer screening among Iraqi women refugees. J Immigr Minor Health. 2012 Aug;14(4):633-9.
Othman RT, Abdulljabar R, Saeed A, Kittani SS, Sulaiman HM, Mohammed SA, Rashid RM, Hussein NR. Cancer incidence rates in the Kurdistan region/Iraq from 2007-2009. Asian Pac J Cancer Prev. 2011;12(5):1261-4.
Runnak MA, Hazha MA, Hemin HA, Wasan AA, Rekawt RM, Michael HD.A population-based study of Kurdish breast cancer in northern Iraq: hormone receptor and HER2 status. A comparison with Arabic women and United States SEER data. BMC Womens Health. 2012 Jun 22;12:16.
Laitman Y, Simeonov M, Herskovitz L, Kushnir A, Shimon-Paluch S, Kaufman B, Zidan J, Friedman E. Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel. Breast Cancer Res Treat. 2012 Jun;133(3):1153-7.
Hemminki K, Mousavi SM, Sundquist J, Brandt A. Does the breast cancer age at diagnosis differ by ethnicity? A study on immigrants to Sweden. Oncologist. 2011;16(2):146-54.
Alwan NA. Breast cancer: demographic characteristics and clinico-pathological presentation of patients in Iraq. East Mediterr Health J. 2010 Nov;16(11):1159-64.
Habib OS, Al-Diab JM, Mohsin AA, Al-Elwe WM, Hasan JG, Al-Haroon SS, Al-Emara KA. Experience and outcome of population-based cancer registration in Basrah-Southern Iraq in 2005-2008.
Busby C, Hamdan M, Ariabi E. Cancer, infant mortality and birth sex-ratio in Fallujah, Iraq 2005-2009.
Majid RA, Mohammed HA, Saeed HM, Safar BM, Rashid RM, Hughson MD. Breast cancer in Kurdish women of northern Iraq: incidence, clinical stage, and case control analysis of parity and family risk. BMC Womens Health. 2009 Dec 11;9:33.
Salim EI, Moore MA, Al-Lawati JA, Al-Sayyad J, Bazawir A, Bener A, Corbex M, El-Saghir N, Habib OS, Maziak W, Mokhtar HC, Seif-Eldrin IA, Sobue T. Cancer epidemiology and control in the arab world - past, present and future. Asian Pac J Cancer Prev. 2009 Jan-Mar;10(1):3-16.
Weiss-Salz I, Harlap S, Friedlander Y, Kaduri L, Levy-Lahad E, Yanetz R, Deutsch L, Hochner H, Paltiel O. To study the Ethnic ancestry and increased paternal age are risk factors for breast cancer before the age of 40 years. Eur J Cancer Prev. 2007 Dec;16(6):549-54.
Najjar H, Easson A. Age at diagnosis of breast cancer in Arab nations. Int J Surg. 2010;8(6):448-52.
Santen RJ, Yue W, Wang JP. Estrogen metabolites and breast cancer. Steroids. 2014 Aug 26.
Su X, Xu X, Li G, Lin B, Cao J, Teng L. ER-α36: a novel biomarker and potential therapeutic target in breast cancer. Onco Targets Ther. 2014 Aug 30;7:1525-33.
Bilal I, Chowdhury A, Davidson J, Whitehead S. Phytoestrogens and prevention of breast cancer: The contentious debate. World J Clin Oncol. 2014 Oct 10;5(4):705-12.
Hapangama DK, Kamal AM, Bulmer JN. Estrogen receptor β: the guardian of the endometrium.
Hum Reprod Update. 2014 Oct 10.
Sestak I. Preventative therapies for healthy women at high risk of breast cancer. Cancer Manag Res. 2014 Oct 17;6:423-30.
Burkman R, Schlesselman JJ, Zieman M. Safety concerns and health benefits associated with oral contraception. American Journal of Obstetrics and Gynecology 2004; 190(4 Suppl):S5–22.
Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347(9017):1713–1727.
