Demographic and Clinical Characteristics of Females with Breast Cancer in Iraq with Respect to Age: A Single-Center Study

Breast cancer is a widespread form of cancer that affects women globally and is the second most common cause of death in women, following lung cancer^[1]. In 2020, 2.3 million women were diagnosed with breast cancer, resulting in 685,000 deaths worldwide. By the end of 2020, 7.8 million women who had been diagnosed with breast cancer within the last 5 years were still alive, making it the most prevalent form of cancer worldwide^[2].

Breast cancer is the most common form of cancer in Iraq and is the primary cause of death among women^[3]. It ranks first among the top 10 malignant tumors affecting the community. In 2016, 897 women died from breast cancer, which accounted for 23.6% of cancer-related deaths among Iraqi females and 12.1% of overall deaths among males and females, second only to bronchogenic cancer^[4,5]. Moreover, there has been a noticeable increase in breast cancer incidence among women aged 70 and above, as well as those aged 40–49 years^[6].

A significant risk factor for breast cancer is having a family history of the disease. Females with a first-degree relative (mother, sister, or daughter) who had breast cancer are at a higher risk of developing the disease themselves^[7]. In addition to genetic predisposition, various factors can contribute to the development of breast cancer among women, including demographic characteristics, clinical and reproductive features, and environmental factors. Advanced age, socioeconomic status, diet, endogenous or exogenous hormones, atypical breast diseases, benign tumors, oncogenic viruses, and exposure to carcinogens have all been linked to an increased risk of breast cancer^[8].

Breast cancer can impact women of all ages, although the likelihood of developing the disease increases with age. Most cases of breast cancer are diagnosed in women over the age of 50, but a small percentage of cases are found in younger women^[9]. Moreover, differences in health-care access and cultural factors can have an impact on disease outcomes among different ethnic groups^[10].

Breast cancer is a complex disease that consists of various histologic subtypes, including invasive ductal carcinoma, invasive lobular carcinoma, and less-common subtypes, each having unique characteristics that affect prognosis and treatment^[11]. The presence or absence of cancer cells in the lymph nodes surrounding the breast is crucial in determining the spread of the disease. Lymph node involvement has a significant impact on treatment options and overall prognosis^[12]. Hormone receptor status, particularly estrogen receptor (ER) and progesterone receptor (PR) status, is also important in guiding treatment decisions and predicting the response to hormone-based therapies^[13]. Metastasis, or the spread of breast cancer to distant sites such as bones, liver, lungs, or brain, has a significant impact on treatment options and prognosis. While metastatic breast cancer (MBC) is incurable, it can be managed with various treatment options^[14].

Treatment of breast cancer in Iraq requires a comprehensive approach that includes surgery, radiation therapy, chemotherapy, targeted therapy, and hormonal therapy. Factors such as tumor stage, hormone receptor status, and patient preferences are taken into consideration^[15]. However, addressing breast cancer in Iraq poses several challenges due to limited resources, infrastructure, and awareness. There is a pressing need for increased investment in breast cancer prevention, early detection programs, and treatment facilities. Moreover, future directions such as integrating genomic profiling, targeted therapies, and supportive care services are necessary to improve patient outcomes^{[16, 17]}.

This paper aims to describe the demographic and clinical characteristics associated with breast cancer among Iraqi women with respect to age. Understanding the demographic and clinical characteristics of females with breast cancer in Iraq is essential for developing targeted interventions, improving early detection, and providing appropriate treatment.

A total of 500 patients were included in the study, of which 37.6% were below 50 years and 62.4% were 50 years and older. The majority were married (80.4%) and resided in Baghdad (81%). The proportion of married patients was significantly higher among those diagnosed under the age of 50 years (89.9%) compared to 74.7% diagnosed above the age of 50 years (p < 0.0001). Only 2% of the patients had their first child after the age of 35; around 19% of women diagnosed above 50 years had their first child when they were younger than 20 years compared to 8.9% of those diagnosed younger than 50 years (p = 0.001). Around 48% of patients diagnosed before 50 years had breast feeding duration between 1 and 3 months compared to 28.5% of women diagnosed after 50 years of age (p < 0.0001). There were no significant differences in personal habits such as smoking, coffee drinking, and physical activity, nor in the age of menarche and family history of cancer between the two groups. The frequency of women having diabetes mellitus, hypertension, hypercholesterolemia, heart disease, and vitamin D deficiency was significantly higher among those diagnosed after the age of 50 (Table 1).

Regarding clinical presentation, 67.8% of the patients had stage 2 tumor and 65.2% had tumor on the left side. Around 50% of the patients had metastasis to the lymph node; moreover, 19.8% and 84.8% had undergone partial mastectomy and total mastectomy, respectively. The majority had ductal carcinoma (92.6%). Eighty-two percent presented with a palpable lump. There was no significant difference with respect to tumor stage, size, lymph node status, presence of palpable lump, bloody nipple discharge, and ulceration between the two groups (Table 2).

Around 66% of the patients received hormone therapy and 82% received radiotherapy. Among patients who were diagnosed after 50 years of age, 34% had metastasis, compared to 22.9% of those diagnosed before the age of 50 (p = 0.009). There was no significant difference in the rate of recurrence between both groups. Mortality rate was 19.6%. Around 23% of patients diagnosed after the age of 50 passed away compared to 12.8% of those diagnosed at a younger age (p = 0.003) (Table 3).

Breast cancer is a prevalent issue worldwide, especially in Iraq. One of the crucial benefits of successful intervention, detection, and treatment is comprehending the demographic and clinical features of women with breast cancer^[18]. In this study, we describe the demographic and clinical characteristics associated with breast cancer with respect to age among Iraqi women attending a private clinic in Baghdad.

In our study, the majority (62.4%) of participants were aged 50 years and older. Similarly, Mutar et al. found that 55% of breast cancer patients in Iraq were above the age of 50^[19]. However, a study conducted between 2004 and 2008 in Iraq reported that 54.1% of patients were younger than 50 years old, indicating a shift in the age distribution of breast cancer cases in Iraq over time^[20]. This trend is also observed in Jordan, where 53.7% of breast cancer patients were over the age of 50^[21]. Moreover, a multicentric, cross-sectional study conducted at three hospitals in KSA from February 2019 to February 2020 reported that the risk of breast cancer increased with age in Saudi Arabia^[22]. Similar findings were reported in Turkey, where Ozsoy et al. noted that the risk of breast cancer increases after the age of 40^[23]. In Lebanon, breast cancer cases were rare among women below the age group of 25–29, but increased significantly with older age groups, with over 90% of patients being 35 years or older. This highlights the importance of supporting guidelines for earlier screening to detect breast cancer at an earlier stage and reduce its burden among Lebanese women^[24]. In the USA, only 19% of breast cancer patients were younger than 50 years old between 2017 and 2018, which may be attributed to the younger demographic profile of the Arab population as suggested by the World Health Organization (WHO) collaborative work^[25].

Our study found that marriage was significantly more prevalent (89.9%) among breast cancer patients under the age of 50, compared to those above the age of 50 (74.7%) (p < 0.0001). A similar study conducted on 1070 Egyptian breast cancer patients revealed that 18.7% were diagnosed before the age of 40, and 79.5% of them were married^[26]. Another epidemiological study on cancer incidence and marital status reported that the increased risk of breast cancer in single females was more pronounced in older age groups, while the increased risks for several types of cancer in divorced individuals were more pronounced in younger age groups. These differences may be partly explained by variations in reproductive factors^[27]. In addition, a meta-analysis conducted by Yuan et al. showed that being married is linked to timely diagnosis and favorable prognosis in cancers of most women. Unmarried female cancer patients have a higher risk of late-stage diagnosis and worse survival outcomes than their married counterparts^[28].

In this study, around 48% of patients diagnosed before 50 years had breastfed for 1–3 months compared to 28.5% of women diagnosed after 50 years of age (p < 0.0001). A collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including over 50,000 women with breast cancer, found that breastfeeding reduces the risk of breast cancer but does not vary with age^[29]. Another study conducted in Germany revealed that breastfeeding for at least 1 month did not provide protection against breast cancer, but the risk significantly decreased with increasing duration of breastfeeding. This reduction in risk was more apparent in women who breastfed for the first time after the age of 25^[30]. The precise mechanisms by which breastfeeding reduces the risk of breast cancer are not yet fully understood, but some theories suggest that it reduces the total number of menstrual cycles a woman experiences over her lifetime, thereby reducing her exposure to hormones associated with breast cancer development. Another theory proposes that breastfeeding induces structural and genetic changes in breast tissue that make it less susceptible to malignant transformation^{[31, 32]}.

In this study, women diagnosed with breast cancer after the age of 50 had a significantly higher incidence of diabetes mellitus, hypertension, hypercholesterolemia, heart disease, and vitamin D deficiency. Meanwhile, a Canadian population-based study discovered that women with breast cancer were more likely to develop various conditions such as ischemic heart disease, heart failure, depression, diabetes, osteoporosis, and hypothyroidism compared to women without cancer. Comorbidities have been linked to a lower quality of life and increased mortality rates in women with breast cancer^{[33, 34]}.

The present study found that 67.8% of patients had early-stage breast cancer (stage II). This could be due to improved knowledge, attitudes, and practices toward breast cancer, leading to earlier reporting. In contrast, other studies in Iraq found that a significant proportion of patients were diagnosed at later stages (stages III and IV). In the study carried out by Mutar et al. in Iraq, it was reported that 42.9% of the patients were diagnosed with stage III and 25% with stage IV cancer, which are considered late stages^[19]. In another study conducted in Maysan governorate in southern Iraq, most of the patients (82.3%) presented with advanced-stage disease, stages II and III^[35]. Late presentation was also found in another Iraqi study^[36], in which 47% of the patients presented with advanced stages of the disease and only 9.8% presented with stage I. Moreover, in a recent study published in 2018^[37], 50.5% of patients had tumor stage III or IV.

Another study conducted in the northern region of Nigeria in 2010 showed that the majority of patients (62%) had advanced-stage disease^[38]. Similarly, a study carried out in Mexico found that 64% of women diagnosed with breast cancer presented at late stages (stages III and IV)^[39]. In a study conducted in a semi-urban tertiary health institution in Nigeria, it was reported that the majority of patients (87.8%) presented with late-stage breast cancer (stages III and IV)^[40]. Several reasons have been identified as contributing to the late presentation of breast cancer, including low levels of education, fear of diagnosis, lack of knowledge, denial, limited access to health-care facilities, and religious beliefs in faith healing^{[41, 42]}.

Our findings showed that approximately 50% of patients had lymph node metastasis, and there was no significant difference in lymph node involvement between the two age groups. A study on clinicopathologic features of breast cancer in Sudan found that a high percentage of Sudanese women (65.5%) were diagnosed with extensive lymph node involvement compared to women in developed countries^[43]. Similarly, a systematic review by Azim et al. reported that 70% of women with breast cancer in Egypt had lymph node metastasis^[44]. The presence of lymph node involvement is an important factor in determining the stage and treatment approach for breast cancer, as well as predicting the likelihood of disease recurrence and overall survival^[45].

Regarding the histopathologic subtype, in our study, the majority of patients had ductal carcinoma (92.6%), while lobular carcinoma accounted for a smaller proportion (6.6%). This is consistent with other studies, which have also found that infiltrating ductal carcinoma without a specific pattern is the most common histopathologic subtype. For example, in a study by Mutar et al., invasive ductal carcinoma was the most common (81.4%), followed by invasive lobular carcinoma (6.9%)^[19]. Similarly, in a study conducted in Jordan, 86.9% of patients had ductal carcinoma^[21]. Another study conducted in Mexico found that 79% of patients had ductal histology^[39]. Razik et al. found that individuals in the age group of 31–45 years were less likely to be diagnosed with ductal/lobular/papillary carcinoma compared to those in the less than 30 years age group^[22]. Certain histologic subtypes of breast cancer are associated with a more favorable clinical outcome, and it is important to consider histologic variety as a prognostic factor when deciding on breast cancer management. Tumors of special types, such as tubular carcinoma, cribriform carcinoma, mucinous carcinoma, adenoid cystic carcinoma, tubulolobular carcinoma, and papillary carcinoma, have been shown to have an excellent prognosis. For these types of tumors, the use of systemic chemotherapy management is generally limited to higher stages of the disease^[46].

In the present study, 82% presented with a palpable lump. Similarly, a study conducted by Alwan et al. found that the vast majority (95%) of Iraqi patients presented with palpable lumps^[26]. As breast lumps are the most common symptom, it is important to emphasize their significance during health awareness programs for women. Health-care professionals should also play a crucial role in educating women on the importance of breast examination during hospital visits, even for other health issues. It is worth noting that more than 90% of breast cancer cases are detected by women themselves, underscoring the importance of breast self-examination for early detection and treatment of cancer^{[47,48,49,50]}.

We also reported that around 66% of the patients received hormone therapy and 82% received radiotherapy. In addition, 19.8% and 84.8% underwent partial mastectomy and total mastectomy, respectively. In a study conducted by Alwan et al., it was reported that the percentage of patients taking hormonal therapy in 2019 was 19.4%, which was significantly lower than the percentage reported for Iraqi patients in 2010 (29%), probably reflecting better orientation to the drawbacks of such medications^[20]. In contrast, a study conducted in Nigeria found that only 4.9% of patients received radiotherapy due to limited availability of radiotherapy facilities and high rates of loss to follow-up^[40]. The management of breast cancer involves multiple modalities and can be challenging for physicians in developing countries due to the advanced stage at presentation and inadequate diagnostic and treatment facilities. The choice of therapy is often dictated by the local availability of resources^[51].

In our study, among patients who were diagnosed after 50 years of age, 34% had metastasis, compared to 22.9% of those diagnosed before the age of 50. The metastasis patterns in different age groups of breast cancer women may indeed still be a subject of controversy and ongoing research. Breast cancer is a complex disease with various subtypes, and its behavior can differ among different age groups, which can affect the patterns of metastasis. A study of 14,403 patients based on the Epidemiological Strategy and Medical Economics (ESME) database found that breast cancer patients aged <40 years were more likely to have visceral metastasis than bone metastasis^[52].

Also, Chen et al. found that MBC patients aged <50 years were more likely to have distant lymph node metastasis and multiple sites of metastasis and less likely to have lung metastasis^[53]. Moreover, a study of 6,640 patients showed that MBC patients aged <40 years were more likely to have brain and liver metastases than patients aged ≥40 years^[54]. In addition, in a study assessing the metastasis patterns of breast cancer patients in China, it was reported that in the younger group (≤40 years old), the proportion of liver metastasis was significantly higher and the proportion of lung metastasis was significantly lower than those of the older group (>40 years old)^[55].

The study found a mortality rate of 19.6%, with a higher rate of 23% found among patients diagnosed after the age of 50 compared to 12.8% among younger patients. The advanced stage at diagnosis is the primary contributor to the higher rates of morbidity and mortality^[25]. In this study, the low mortality rate is due to the fact that 67.8% of the patients had tumor stage II, which is an early-stage presentation, which explains why the mortality rate in this study was low. Moreover, the mortality rate of breast cancer varies among different age groups. Breast cancer mortality is influenced by various factors, including early detection, access to health care, treatment options, tumor characteristics, and overall health status of the individual^[56].

This study is limited by its retrospective single-center design, which may result in biased outcome. Conducting the study in a single center might limit the diversity of the study population, leading to potential underrepresentation or overrepresentation of certain age groups or demographics. Moreover, the results may be influenced by local practice patterns and institutional variations, limiting the study’s applicability to diverse populations. Caution should be exercised when extrapolating findings beyond the study site. However, the study has some strengths. This study offers a snapshot of the demographic and clinical characteristics of females with breast cancer in Iraq. By capturing data from various age groups, it provides a comprehensive picture of the disease’s prevalence across different stages of life. Moreover, by providing current and relevant data on breast cancer in Iraq, the study can serve as a benchmark for future research and comparison with similar studies conducted in different regions or over time.

In conclusion, this study provided valuable insights into the prevalence and distribution of breast cancer among females in Iraq concerning age-related factors. A considerable proportion of breast cancer patients in Iraq is still present with locally advanced disease at the time of diagnosis. Understanding the demographic and clinical characteristics of females with breast cancer in Iraq is crucial for developing effective strategies to combat the disease. By addressing the specific challenges faced in Iraq, health-care providers and policymakers can work toward reducing the burden of breast cancer and improving the quality of life for affected women. Moreover, it justifies the necessity to promote public awareness educational campaigns to strengthen national early detection program as well as to establish national protocol guidelines for early detection, diagnosis, and treatment of the disease.