View of Demographic and Clinico-Pathological Characteristics of Some Iraqi Female Patients Newly Diagnosed with Breast Cancer

(1)

Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 6, 2021, Pages. 8264 - 8278 Received 25 April 2021; Accepted 08 May 2021.

Demographic and Clinico-Pathological Characteristics of Some Iraqi Female Patients Newly Diagnosed with Breast Cancer

Adel Omran Salman¹, HazimaMossa Al-Abassi¹, WafaaSabri Mahod¹

1Department of Biology, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq.

*E-mail: [email protected] Abstract.

Breast tumors are the most common carcinoma in women of all ethnicities and races, and are the primary cause of premature mortality among women , early detection is associated with reduce mortality. The majority of breasttumors begin in the lactiferous ducts , which carry milk to the nipple , some begin in the lobule cells ,which are the milk producing cells.

breasttumor is worldwide second most common cancer and the most tumor to be diagnosed in womens. breasttumors are ranks first among the Iraqi population for 30 years and are now forming a major public health problem being the second cause of death for women.

Aim: This study was aimed to assess and highlight the clinical and demographical profiles of Iraqi women with breast tumor and correlate the distribution of breast tumor in Iraqi Arab women with these demographic and clinicpathological characteristics such as the age of women patients, histologic grade, stage, type and side of the tumor, location, menstruation , hormonal intake , tumor size, lymph node metastasis, Body mass index, family history and others. This is a descriptive study was done at the oncology teaching hospital of the medical city in Baghdad . Sixty cases of newly diagnosis of breast cancer women (mean age 51.18±10.64) were enrolled in this study during the period May 2019-february 2020. Their age range was 30-71 years and 40 healthy women were matched with patients as control (mean age 45.30±9.36), There age range was 30-64 years. Questionnaire of self -evaluation were used to collect personal and sociodemographic data in interviews with the patients directly: clinical and histologic characteristics of the patients tumors were collected via their medical records. Medical notes and histopathological reports of patients which confirmed diagnosis of breast cancer affected. Ethical approval was obtained. The average age at diagnosis was 51 years. The highest incidence of breast tumor recorded among patients women in the category of => 50 years (56.7%) followed by category of 40-49 years (25 %).

The most common histopathological type was Invasive ductal carcinoma (IDC) (91.7%) , followed by Invasive lobular carcinoma(ILC) (8.3%). The rates of positive Estrogen (ER),Progesterone (PR) and Epidermal growth factor receptor HER2/neutumor contents were 80% , 75% and 23.3% respectively. 50% of the tumors lesion were found in the left breast . location of the tumor more frequent in upper outer quadrant (46.7%), followed by retroareolar (20%). breast cancer is common in married women (95%). Majority of the patients (76.7%) were moderately differentiated (grade II). The most common stages at diagnosis were stages II (43.3%) and stage III (30.0%) in the TNM system. Positive lymph node metastasis was noted in 61.7% . This study shows that there were 51.7% of breast cancer women in pre-menopausal age and 48.3% of women were in post-menopausal age. The body mass index of women revealed that the majority of the patients and control were either obese (55.0%) or had overweight (33.3%). History of breast tumor and other cancers were recorded in 31.7%; 36.3% respectively,while 68.3% and 63.3% of patients have no history of breast tumor and other cancers. Hormonal intake was demonstrated in 48.3% of patients .the percentage of smokers was observed in 8.3% of patients ,while the nonsmoker was 81.7%

and 10% in passive. At the time of the first presentation in Iraq, breast tumor is still diagnosed at relatively advanced stages. Early detection is the key method for managing the

(2)

disease of breast tumor in the short term, and essential for initiation of prompt therapy and reduction of mortality. Breast tumor in Iraq has been a significant threat to women's lives..The highest incidence of breast tumor noted among women in their sixth and fifth decades of life. most of the breast tumor patients in the current study were estrogen and progesterone (hormonal ) positive. Regular -long term follow up through multidisciplinary cancer boards in mandatory to monitor response to therapy and recurrence.

Keywords.Demographic, Clinico-pathological characteristics, Breast cancer, Iraqi patients.

1.Introduction

Breast tumor is a group of diseases in which cells in breast tissue change and divide uncontrolled, usually leading to mass or lump [1]. Its can begin from various parts of the breast [2]. Breast tumor is the second most common tumor in the world and the most common tumor to be diagnosed in women ( 24.2% i.e. about one in 4 of all new cancer cases diagnosed in women worldwide are breast tumor [3]. In 2018 there were an estimated 2.1 million new breast tumor cases diagnosed constituting (11.6% ) of all tumor cases in women and 627.000 (6.6%) breast tumor death worldwide [4, 5, 6]. The age-standardized incidence and mortality rates per 100, 000 for the breast tumor in 2018 in countries with high or very high human development Index (HDI) was (54.4 ; 11.6/100000), compared with countries with low or medium HDI, was (31.3 ; 14.9/100000 ) in women [7]. The incidence rates of breast tumor vary dramatically across the globe, being always highest in more developed regions, namely; Australia, New Zealand and Western Europe (more than 90 new cases/100000 women annually), North America (85 new cases/100000 women annually ), compared with less than 30/100000 women annually in developing regions like Eastern Africa,Middle Africa and South Central Asia [4, 5]. Incidence and mortality data remain extremely limited for several world regions, such as Africa [7]. The World Health Organization ( W.H.O.) reveals that the incidence rates of breast tumors are steadily increasing in countries of the Eastern Mediterranean Region EMR including Iraq, with annual rise ranging between 1% to 5% [8]. The age -standardized incidence and mortality rates per 100,000 in Iraq was (38,4 & 13.6/100000), compared to the countries surrounding Iraq including Turkey (46& 11/100000) , Iran (31 & 9/100000 ), Saudi Arabia (27,3

&7.5/100000) , Kuwait (53,4&18/100000) , Syria (67,3&27/100000) and Jordan (57,4&18.5/100000) [5, 6]. While in Egypt was (52,4&21,3/100000), Lebanon (97.6&25,3/100000), United Arab Emirates (53&17/100000), Qatar (42,1&14/100000), Globally , The age -standardized incidence and mortality rates per 100000 in United states of America was (84.9 &12.7/100,000), Canada (83.8&12.1/100,000), United Kingdom (93.6&14.4/100,000), Germany (85.4&15.7/100000), Australia (94.5&12.3/100000), China (36.1&8.8/100000) and Japan (57.6&9.3/100000) [5]. Many females who have one or more breast tumor risk factors never develop breast carcinoma, while a most females with breast tumor have no known risk factors. Some risk factors, like a person's age or race, can't be changed. Other risk factors are related to tumor-causing factors in the environment or to personal behaviors [2]. In Iraq, breast tumors are considered the most common tumor [9]. It ranks the first among the commonest malignancies among all the population [10]. There were 6206 cases in 2018 considered 6094 females and 112 males, the percentage of total constitute around 19.7 % with rate 16.3 for every 100,000 populations [11]. Iraqi reports show that women among middle age have the highest incidence rates of breast tumor and that over 40% of the cases remain diagnosed at advanced stages [12, 13]. Globally , The number of breast tumor cases increased from 1.7 million new cases and 522,000 deaths in 2012 to 2.1 million new cases and 626,000 deaths in 2018 . and the prevalence rate of all women breast

(3)

tumor (all ages) increased from 43 per 100,000 to 46 per 100,000 in 2018, which became one of the biggest threats to women health [4, 6]. The incidence rate is estimated to reach 3.2 million by 2050 [14].The main purpose of this study was to analyze the characteristics of breast tumors with a sample of Iraqi Arab population newly diagnosed with the breast tumor an age period between less than 40 years to equal or more than 50 years. Focusing on the demographic and clinico-pathological profiles.

2.Materials and Methods

This retrospective study was conducted among Iraqi Arab patients entered the Oncology Teaching Hospital of the medical city in Baghdad.from May 2019 to February 2020. A total of 60 female breast cancer patients were seen( mean age 51.18±10.64). the age range between 30-71 years. The diagnosis was made by the consultant medical staff at the Oncology teaching hospital according to the clinical mamographic, histological findings.

Patients were early detected, none of the patients received chemotherapy or radiotherapy or treatment with mastectomy . In addition to patients , 40 healthy women (controls) ( mean age 45.30 ± 9.36 ), matched patients for ethnicity (Iraqi Arabs), Their aged range between 30-64 years. All examined women were residence in different areas of Baghdad, and other governorate. The analyzed sample comprised the questionnaire . The questionnaire was designed and conducted at the oncology teaching hospital, included a set of questions that displayed the correlation of several demographic and clinical characteristics of the affected patients of breast carcinoma. Histopathology reports and immunohistochemical (IHC) results to confirm patients’ hormonal status, including ER, PgR, and HER-2/neu results, were obtained. The women enrolled in this study had already been newly diagnosed with breast cancer . Data for most women were obtained from the Oncology Teaching Hospital laboratory, the cancer registry, and patients records, which included histopathological reports confirming their diagnosis with regard to breast cancer subtypes, grading, and radiological staging. Were data identified and collected from the patient files . The studied variables were recorded from the database of the information system and the case sheet records of the oncology teaching hospital of the medical city in Baghdad, the referral center for early detection of breast tumors. Demographic and Clinico-pathological parameters included the age of patients at the time of diagnosis, body mass index, tumor side and tumor location,tumor size, lymph node metastasis, marital status, menstruation, hormonal intake, smoking, educational level, family history of breast or any other tumor . World Health Organization WHO histological typing of breas carcinoma [15]. Tumor grade (following modified Nottingham Bloom Richardson) [16]. And the clinical stage of the disease at presentation (defined according to the UICC TNM Classification System) [17]. The IBM SPSS version 26.0 computer program was used . For non-parametric data, Pearsons chi- square (χ²test) used to calculate the probability. A Pearsons correlation used to determine the relationship between the studied parameters

3. Results and Discussion

Table (1) and figure (1-A) illustrates the demographic characteristics of the studied patients.

With average age (51) years range (between 30-71 years). The peak age frequency has occurred with the age group ( => 50 years ) were 56.7% . Only 18.33% were under the age of 40 years, while 25.0% were aged 40-49 years . The body mass index (BMI) average was (30.5) Kg/m2 with range ( between 18.97-45.9), and the percentage were (11.7%,33.3% , 55.0%) respectively . The results of current study showed that most patients carried the lesion of the tumor in the left breast 50 % and 45 % in the right breast and only 5% carried lesion in bilateral . The upper outer quadrant (UOQ) was the most common location of a tumor in

(4)

breast , it was found in 28 cases (46.7%) followed by the retroareolar region in 12 cases (20

%),other locations are summarized in Table (1). Approximately 95% of the patients were married . Results confirmed that the percentage of breast cancer was 36.7% in illiteratedwomen ,whereas 63.3% in educated women. There were 51.7% of breast cancer women in premenopausal age and 48.3% of women were in postmenopausal age. History family of breast cancer and other cancers registered positively in 31.7% and 36.7%

respectively , while 68.3% and 63.3% of patients have no history of breast cancer and other cancers(negatively). The percentage of smokers was observed in 8.3% of patients , while the nonsmoker was 81.7% and 10% in passive smoker. Hormonal intake was demonstrated in 48.3% of patients while 51.7% of patients have not hormonal intake. There were highly significant differences recorded between the most demographic characteristics of breast tumor women at p≤0.05.

Table 1. The distribution of breast tumor women according to demographic characteristics.

Variables Patients (N=60) Percentage% Chi-square P-value

All patients 60 -

Average age 51 -

Age mean±SD 51.18±10.64

Age(years)

<40 40-49

=>50

60(30-71) 11 15 34

18.3 25.0 56.7

22.650*

1.2 x 10^-5 Body mass index /BMI (Kg/m2)

Normal Overweight Obese

60(18.97-45-91) 7

20 33

11.7 33.3 55.0

40.950*

1.2 x 10^-9 Tumor site

Right Left Bilateral

27 30 3

45.0 50.0 5.0

32.850*

7.4 x 10^-8 Tumor location

Upper outer quadrant (UOQ) Upper inner quadrant (UIQ) Lower outer quadrant (LOQ) Lower inner quadrant (LIQ) Retroareolar

28 8 5 7 12

46.7 13.3 8.3 11.7 20.0

36.042*

2.8 x 10^-7

Marital status Married Single

57 3

95.0 5.0

97.20*

6.3 x 10^-23 Educational level

Illiterated Educated

22 38

36.7 63.3

8.533*

0.003 Menstruation

Premenopausal Postmenapausal

31 29

51.7 48.3

0.133 0.715 NS Family history of BC

YES NO

19 41

31.7 68.3

16.133*

5.9 x 10^-5 Family history of other cancer

YES 22 36.7 8.533*

(5)

NO 38 63.3 0.003

Smoking Yes NO Passive

5 49

6

8.3 81.7 10.0

94.650*

2.8 x 10^-21 Hormonal intake

YES NO

29 31

48.3 51.7

0.133 0.71 NS

*Significant difference between percentages using Pearson Chi-square test (χ²-test ) at 0.05 level.

The clinico-pathological characteristics of the patients are summarized in Table (2) and figure (1-B). The patients were divided into two groups according to clinical characteristics, Invasive ductal carcinoma (IDC) and Invasive lobular carcinoma (ILC),the number and percentage for each type was 55(91.7%) and 5(8.3%) respectively. Histological tumor grades were (1.7%,76.7% and 21.7%) for well differentiated (GI), moderately differentiated (GII) and poorly differentiated (GIII) respectively. Stage II and stage III were 43.3% and 30 % respectively. While stage IV (15 %) , and stage I (11.7%) . High percentage of patients 46(76.7%) were with more than 2 cm tumor size. Therty –seven patients 61.7% had lymph node metastasis ,while 38.3% had not. There were highly significant differences recorded between the most clinico-pathological characteristics of breast tumor women at p≤0.05.

Table 2.Clinico-pathological characteristics of breast tumor patients.

Characteristics Patients (N=60) Percentage % Chi-square P-value Tumor type

Invasive ductal carcinoma (IDC) Invasive lobular carcinoma (ILC)

55 5

91.7 8.3

83.333*

6.9 x 10^-20 Tumor grade

Grade I ( Well differentiated) Grade II ( Moderately

differentiated)

Grade III ( Poorly differentiated)

1 46 13

1.7 76.7 21.7

81.450*

2.1 x 10^-18 Tumor stage

Stage I Stage II Stage III Stage IV

7 26 18 9

11.7 43.3 30.0 15.0

20.444*

1.4 x 10^-4 Tumor Size(cm)

≤2cm

>2cm

14 46

23.3 76.7

34.133*

5.1 x 10^-9 Lymph Node Metastasis

Positive Negative

37 23

61.7 38.3

6.533*

0.011

*Significant difference between percentages using Pearson Chi-square test (χ2-test ) at 0.05 level.

(6)

A- Demographic characteristics B-Clinico-pathological characteristics Figure 1.Distribution of demographic (A) and clinico- pathological characteristics (B) of breast tumor patients.

According to the TNM staging of this study , the T2 was predominant stage 37 (61.7%) , followed by T1 and T3 as 14(23.3%), 8(13.3%) respectively .The T4 stage is only seen in 1(1.7%). The results showed a high percent of N0 stage in 23 (38.3%) and were followed by N1 in 17 (28.3%) , N2 in 11 (18.3%) , and N3 in 9 (15%) . also the results showed a high percent of M0 stage in 51(85%) and were followed by M1in 9(5%). As shown in Table (3).

There were high significant differences recorded between Tumor-Node-Metastasis characteristics at (p≤0.05).

Table 3. Distribution of breast tumor women depend to Tumor-Node-Metastasis characteristics (TNM).

Characteristics Patients (N=60) Percentage(%) Chi-square P-value TNM stage

Tumor size T0

T1 T2 T3 T4

0 14 37 8 1

0.0 23.3 61.7 13.3 1.7

94.792*

1.3 x 10^-19 Nodal status

N0 N1 N2 N3

23 17 11 9

38.3 28.3 18.3 15.0

10.667*

0.014 Metastases

M0 M1

51 9

85.0 5.0

58.800*

1.7 x 10^-14

(7)

The stage and grade of the different types of breast cancer were illustrated in Table (4). In respect to IDC, (12.7% ) of which were discovered at the first stage I ,and the rest at the second stage II (43.6%),third stage III (29.1%) and forth stage IV (14.5%) respectively.

Similarly, 78.2% of IDC at intermediate grade (GII) and 21.8% at high grade (GIII). While 60 % of ILC discovered in intermediate grade (GII) and the rest were discovered at high and low grade (20%) respectively . The majority of ILC were discovered at second and third stage (40 %), while the minority of ILC were discovered at fourth stage (20 %). There were high significant differences between the grade of the different twokinds of breast tumor at (P≤0.05), while no significant differences between stage of the different two kinds of breast tumor at (P≤0.05).

Table 4. The major types of breast cancer according to histological classification.

Variables

Types of breast cancer

Chi-square P-value IDC

Total no=55

ILC Total no=5

NO % NO %

Stage

I 7 12.7 0 0.0

0.923 0.820 NS

II 24 43.6 2 40.0

III 16 29.1 2 40.0

IV 8 14.5 1 20.0

Grade

I 0 0.0 1 20.0

11.205*

0.004

II 43 78.2 3 60.0

III 12 21.8 1 20.0

This study included different stages and grade. The result of stage was : І A (4/60, 6.7%), І B (3/60, 5%), ІІA (16/60, 26.7%), ІІB (10/60, 16.7%), ІІІ A (10/60, 16.7%), ІІІ B (0/60, 0 %), ІІІ C (8/60, 13.3%) and IV (9/60, 15 %). There was a high significant difference recorded in different stages and grade at (P≤ 0.05) as shown in (Table 5).

Table 5. Distribution of study samples according to stage and histological grade.

Characteristics Number

(N=60) Percentage (%) Chi-square P- .value

Stage

IA 4 6.7

26.819*

3.6 x 10^-4

IB 3 5.0

IIA 16 26.7

IIB 10 16.7

IIIA 10 16.7

IIIB 0 0.0

IIIC 8 13.3

IV 9 15.0

Total 60 100

Histological grade

I 1 1.7

81.450*

2.1 x 10^-18

II 46 76.7

III 13 21.7

Total 60 100

(8)

The hormone receptor status for Estrogen (ER), Progesteron (PR) and Epidermal growth factor receptor (HER2/neu ) are 80%, 75% and 23.3% have positive hormone receptors, respectively, While 20% , 25% , 76.7% have negative hormone receptors , respectively as shown in Table (6). There were high significant differences recorded between hormone receptor status for ER, PR and HER2/neu at (P≤0.05).and there were high significant differences according to the immunohistochemistry IHC score for ER,PR and HER2/neu at (P≤0.05) as shown in Table (6).

Table 6. Distribution of sample study according to results of hormones and IHC score.

Hormone Patients (N=60) Percentage (%) Chi-square P-value Estrogen receptor (ER )

Positive Negative Total

48 12 60

80.0 20.0 60%

43.200*

4.9 x 10^-11 Strong +ve

Moderate +ve weak positive +ve

36 9 3

15%

5%

56.0*

4.2 x 10 ^-12 Progesteron(PR )

45 15 60

75.0 25.0

30.0*

4.3 x 10^-8 Strong +ve

Moderate +ve weak positive +ve

24 15 6

40%

25%

10%

13.484*

3.7 x 10^--3 HER-2/new receptor

14 46 60

23.3 76.7

34.133*

5.1 x 10^-9 Score 0 (-ve)

Score+1(-ve) Score+2(weak-ve) Score+3(+ve)

36 10 1 13

60%

16.7 1.7 21.7

59.200*

8.7 x 10^-13

*Significant difference between percentages using Pearson Chi-square test (χ²-test ) at 0.05 level Patients age was ranged from (30-71) years , women < 40 years were 11 cases , women from 40-49 years were 15 cases and women =>50 were 34 cases. The age distribution in the present study results showed that a peak age frequency of tumor occurred in the category of

=>50 years at the percentage (56.7%).And was followed by the category 40-49 years (25%) . while in control the most common age belonging to group 40-49 years 15 (37.5%), followed by group =>50 years 14(35%) and 11(27.5%) from control < 40 years old. As shown in Table (7) and figure (2) . There were no significant differences recorded between ages in patients and control (study groups )at (P≤0.05).

(9)

Figure 2. Distribution of breast tumor according to age in study group.

Body mass index (BMI) of women revealed that the majority of the patients and control were either obese (=>30 Kg/m²) found in (33/60, 55%) in patients and (19/40, 47.5%) in control or had overweight (25-29.9 Kg/m²) found in (20/60 33,3%) in patients and (13/40 32.5%) in control respectively. The normal BMI (18.5-24.9 Kg/m2) was found in (7/60, 11.7%) of patients and in (8/40, 20%) of control. As shown in Table (7) and figure (3). There were no significant differences between BMI in patients and control under (P≤0.05).The current study recorded the most common age in patients belonging to group =>50 years 34(56.7%) , followed by group 40-49 years as 15(25 %) and 11(18.3%) from patients were <40 years.

while in control the most common age belonging to group 40-49 years 15(37.5%), followed by group =>50 years 14(32.5%) and 11(27.5%) from control <40 years. There were no significant differences between the study group in age and BMI under (P≤0.05). as shown in (Table 7).

Table 7. Comparison between patients and control in Age and BMI.

Variables

Patients Total NO=60

Controls Total NO=40

Chi- Square P-value

NO % NO %

Age (years)

<40 40-49

=>50

11 15 34

18.3 25.0 56.7

11 15 14

27.5 37.5 35.0

4.514 0.105NS Mean ±SD

(Range)

51.18 ± 10.64 (30-71)

45.30 ± 9.36

(30-64) 0.005*

BMI (Kg/m²)

Normal ( 18.5- 24.9 ) Overweight (25-

29.9) Obese (=>30)

7 20 33

11.7 33.3 55.0

8 13 19

20.0 32.5 47.5

1.376 0.503 Mean ±SD

(Range)

30.78 ± 5.66 (18.97-45.9)

29.69 ± 5.36

(20.0-39.5) 0.337NS

*Significant difference between percentages using Pearson Chi –square test ( χ2 -test ) at 0.05 level. Significant difference between two independent means using Student-t –test at 0.05 level

(10)

Figure 3. Distribution of breast tumor according to BMI in study group.

Age Property showed the highest significant increase in the patient (mean) (51.18 ± 10.64) as compared with control (45.30 ± 9.36) (P≤0.01). Body mass index (BMI) recorded a non- significant increase in patient (30.78 ± 5.66) compared to control (29.69 ± 5.36) as shown in (Table 7).

4. Discussion

The In Iraq breast tumor considered the most common carcinoma [9]. The incidence of breast tumor in Iraqi female increased in the last two decades and forms one of the major threats to female health [18] . The results of the current study noted that breast tumor is more frequent in the left breast, this result agreed with other studies indicated that Iraqi patients mostly carried the tumor on the left side [19, 20, 21, 22, 23] . And disagreed with other study indicated the common patients carried tumor on the right side [24, 25, 26, 27, 28].The upper outer quadrant (UOQ) was the most common location of tumor in breast 46.7% ,followed by the retroareolar region 20% This result agreed with other Iraqi studies [24, 29] which indicated that tumor location in Iraqi patients women mostly found in The upper outer quadrant (UOQ). Age remains the number one independent risk factor associated with breast tumor [30]. Breast tumor is rare in women under the age of 35 years ,however, after that age the incidence begins to increased. More than 80% of cases occur in women over 50 years of age [31]. The age distribution in the present study results showed that a peak age frequency of tumor occurred in the category of => 50 years at percentage (56.7%).and followed by the category 40-49 years (25%) . This result agreed with other Iraqi studies that pointed to the height percentage of patients in category of =>50 years such as [28, 32, 33, 34, 35, 36]. In contrast, this study results has been disagreeing with the other Iraqi studies such as [19, 21, 23, 26, 37, 38] which illustrated that the most patients with breast tumor noted in the category of 40-49 or 40-50 year. In Iraq in this time ,breasttumor developed at an early age about 25 years ( personal communication). Breast tumor in younger women appear in advanced stages, large size , weaker survival , and positive lymph nodes [14]. Women more than 50 years of age accounted for approximately 78% of new breast tumor cases and 87% of breast tumor-related deaths in 2011 in the United States [39], however, the worldwide prevalence of breast tumor among younger women has increased [40, 41]. As shown in Table (7) the anthropometric parameters which included age and BMI in patients and control , the mean for the two properties were (51.18 ± 10.64, 30.78 ± 5.66) respectively in patients as compared with control (45.30 ± 9.36, 29.69 ± 5.36) respectively. The results noted that there were highly significant increase recorded in age mean for patients compared to control by using T test (P≤ 0.05), but in the BMI there were no significant differences in patients as

(11)

compared to control. This study has been agreement with another study illustrated the high significant between patients and control and highest percentage of patients were obese [32, 36]. And disagreed with other study indicated the highest percentage of patients were overweight [26, 42]. This study found that the tumor largest diameter percentage in cases were 76.7 % for ˃ 2 cm and 23.3 % for ≤ 2 cm and these results consistent with [43] and [44]

which showed 90% ; 91.9% of cases had tumor size more than 2 cm , while 10%; 8.1% had tumor size less than 2 cm. The findings obtained in this study could be explained by poor health education and the ignorance of the Iraqi women to the importance of breast self- examination and early medical consultation. These results also were in concordance with results observed by [45] and [46]. In contrast to our study a result from a Western society indicates that the largest percent of the breast cancer tumors were predominantly less than 2 cm [47]. This may due to the early detection programs that are prevalent in the Western countries. The histological examination showed that the invasion of axillary lymph nodes were seen in 37 cases (61.7%), while 23 cases (38.3%) had no lymph node tumor invasion .The status of the axillary lymph nodes is the most important single prognostic factor for all except a small subset of breast carcinomas. Nodal metastasis are strongly correlated with tumor size and other number of invasive carcinoma [48]. This result agreed with other Iraqi studies [20, 44, 49]. And disagreed with other study such as [19]. The majority of breast tumor in Iraqi women included in this study was invasive breast carcinoma (100 %) in which invasive ductal carcinoma constitute 91.7 % and invasive lobular carcinoma about 8.3% . and this result agreed with other Iraqi studies [26, 36, 50, 51, 52, 53, 54] and other Arabic study,77.1% in Morocco , 78.2% in Saudi Arabia [55, 56] that mentioned to the IDC is the common histological type in breast tumor patients. While the histological tumor type Invasive lobular carcinoma ILC in present study was a lower compared with other studies and the percentage was (15.3% ) in Morocco, (3%) in Saud Arabi, (4.2%) in Korea( 4.5% ) in Iraq [51, 56, 57, 58]. According to the TNM staging of this study , the T2 was predominant stage 37 (61.7%) , followed by T1 and T3 as 14(23.3%) , 8(13.3%) respectively .The T4 stage is only seen in 1(1.7%). The results showed a high percent of N0 stage in 23 (38.3%) and were followed by N1 in 17 (28.3%) , N2 in 11 (18.3%) , and N3 in 9 (15%) . Also the results showed a high percent of M0 stage in 51(85%) and were followed by M1in 9(5%).

This result agreed with other Iraqi studies [34, 51, 52, 53, 58]. This study showed that 43.6%

of invasive ductal carcinoma found in stage II and 78.2% in grade II ,while 40% of invasive lobular carcinoma showed in stage II,III and 60% in grade II. This result consistent with [50]

which showed 59.2% of invasive ductal carcinoma in stage II and 50% in grade II . while invasive lobular carcinoma showed 100% in both stage and grade II. As shown, grade ІІ has the highest frequency followed by grade ІІІ. The results of the present study expressed that at the time of diagnosis the most of the patients were in stage ІІ followed by stage ІІІ and stage IV in addition to the pathological changes in the cancer cells that indicated the highest percentage of patients in grade ІІ followed by grade ІІІ at the time of diagnosis . These results agree with Iraqi studies that pointed to the high percentage of patients in stage ІІ and grade ІІ followed by patients with stage ІІІ and grade ІІІ [9, 24, 26, 50, 51, 52, 53, 59]. In contrast, these results disagree with the other Iraqi study that pointed the most of patients with stage ІІІ and grade ІІІ followed by patients with stage and grade ІІ [20]. The current study revealed from all of the 60 cases were tested for ER by IHC method, results showed that 12 cases (20

%) stained negative whereas , (48) cases 80 % showed positive expression, In positive cases, 5 % were showed weak positive, 15 % were moderate positive and 60 % were strong positive for ER as shown in the Table (6). There were highly significant differences under (P≤0.05).The women with ER-negative tumors have very early recurrence,also poor response to endocrine therapy and survival rate decrease compared to ER-positive tumors. From total 60 breast carcinoma of breast stained for PR, 15 cases (25 %) were negative for PR

(12)

expression. and 45 cases (75 %) were positave for PR expression. In positive cases 40 % were strong positive ,25 % moderate staining and 10 % were weak staining by immunohistochemistry. There were highly significant differences under (P≤0.05). The presence of the hormone receptors estrogen and progesterone in a patients breast tumor is an example of a weak prognostic but strong predictive biomarker. If a patients tumor expresses estrogen and /or progesteron ,we can predict that this patient will positively benefit from endocrine therapy [60]. From total 60 cases of breast carcinoma cases, 14 (23.3%) were completely stained cell membrane (positive for HER2/neu expression), 46 (76.7%) were negative (score0 and score1).From 14 positive (1) cases (1.7%) were complete however there were weak or moderate membranous staining In >10% of tumor cells (score 2+) and 13 cases (21.7%) were strong complete membranous staining in >10 of cancerous cells (scored 3+), as shown in the (Table 6). There were highly significant differences recorded under (P≤0.05). The overexpression of the Oncogene HER2/neu in a patients breast tumor is an example of both a prognostic and predictive biomarker.HER2/neu expression is associated with poor prognosis ( high risk of recurrence), it also predicts that a patient will more likely benefit from anthracycline and taxane –based chemotherapies and therapies that target HER2/neu,but not to endocrine-based therapies [60].

5. Conclusion

Breast tumor has become a major threat to female in Iraq . highest incidence of breast tumor in the studied patients was seen =>50 years ( 56.7%) in 6th,7th decades of life and the most common tumor size according to the TNM staging system was T2 (61.7%), beside the most common assessed axillary lymph nodes was N0 and N1 (38.3%; 28.3%) respectively. The IDC was most common histopathology. The hormonal positive recorded more frequent than negative, while inverse in the HER2/neu .the breast cancer more distribution in grade II and stage II. Most patients carried lesion of the tumor in the left breast (50%). There were a highly significant differences recorded at p≤0.05 between the most demographic and clinicpathological characteristics of breast tumor women.

6.References

[1] American Cancer Society 2019 Cancer Facts and Figures 2018Atlanta :American cancer society,Inc.

[2] American Cancer Society 2014Breast cancer.

[3] International Agency for Research on Cancer. World Health Organization 2018Latest global cancer data:Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018.

[4] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A 2018 Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries Cancer J. Clin. 68 394.

[5] Globocan 2018 World health organization .International agency for research on cancer (IARC).

[6] Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, Znaor A and Bray F 2019 Estimating the global cancer Incidence and mortality in 2018:

Globocan sources and methods Int. J. Cancer144 1941.

[7] International Agency for Research on Cancer.World Health Organization 2020World cancer report cancer research for cancer prevention.

(13)

[8] Kulhanova I, Bray F, Fadhil I, Al-Zahrani A S, El-Basmy A, Anwar WA, Al-Omari A, Shamseddine A, Znaor A and Soerjomataram I 2017 Profile of cancer in the Eastern Mediterranean region: the need for actionCancer Epidemiol. 47 125.

[9] Alwan NAS, Mualla FH, Al-Naqash M, Kathum S, Tawfiq FN and Nadhir S 2017 Clinical and pathological characteristics of triple positive breast cancer among Iraqi patientsGulf J. Oncol.1 51.

[10] Ministry of Health in Iraq 2018Annual statistical report 322.

[11] Ministry of Health in Iraq 2020Annual statistical report299.

[12] Alwan N 2014 Iraqi initiative of a regional comparative breast cancer research project in the Middle East. J. Cancer Biol. Res. 21016.

[13] Alwan N and Kerr D 2018 Cancer control in war-torn IraqLancet Oncol. 19291.

[14] Momenimovahed Z and Salehiniya H 2019 Epidemiological characteristics of and risk factors for breast cancer in the worldBreast Cancer Targets Therap. 11 151.

[15] Lakhani SR, Ellis IO, Schnitt SJ, Tan PH and van de Vijer MJ2012World health organization classification of tumours of the breast.4th edition,world health organization classification of tumors ,volume4, International agency for research on cancer,Lyon.

[16] Elston CW and Ellis IO 2002 Pathological prognostic factors in breast cancer.I.The value of histological grade in breast cancer : experience from a large study with long – term follow up Histopathology41 154.

[17] Sobin LH, Gospodarowicz MK and Wittekind C 2011TNM classification of malignant tumors New York,NY, John Wiley Sons.

[18] Al-samarai AM and Abdula SS 2015 Breast cancer frequency rate shift toward younger age in Iraq. IJSRSET. 1 407.

[19] Mahmoud MM 2014 Breast cancer in Kirkuk city, Hormone receptors status (estrogen and progesterone) and Her-2/neu and their correlation with other pathologic prognostic variablesDiyala J. Med. 6 1.

[20] Al-hamadawi HA, Al-Kashwan TA, Al-Janabi AA, Al-Bideri AW, Allebban ZS, Jaber AH and Al-Ghazali HR 2015 Interaction between Altered P53 and PTEN Inactivation has a biological predictive implication in assessment of aggressive breast cancerInt. J.

Curr. Microbiol. App. Sci. 4 910.

[21] Al-Isawi AOJ 2016 Breast cancer in Western Iraq: clinicopathological single institution studyAdv. Breast Cancer Res. 5 83.

[22] Al-Bedairy IH, Al-Faisal AHM, Al-Gazali HR, Al-Mudhafar H 2020 Molecular subtypes by immunohistochemical for Iraqi women with breast cancerIraqi J.Biotechnol.

19 18.

[23] Ghafel HH and Mohseen WT 2019 Assessment of breast tumors among Iraqi women at women health center in Baghdad city :comparative studyIndian J. Foren. Med. Toxol. 1.

[24] Mustafa AA, Hasan NAS and Khalel EA 2016 Imaging and clinicopathological characteristics of breast cancer among women under the age of 40 yearsJ. Facul. Med.

58 140.

[25] Al-Bayati MR 2018 Left Ventricular Dysfunction in Breast Cancer Patients Receiving Trastuzumab: An Observational Study in a Cohort of Iraqi Breast Cancer PatientsThi- Qar Med. J. 15 105.

[26] Abdulkareem ZJ 2018Immunological and molecular study of IL-33 and ST2 receptor in a sample of Iraqi patients with breast cancer MSc.thesis. university of Baghdad , college of education for pure science (Ibn-Al-haitham) 133.

[27] MahoodWS, Mohammed MJ, Mayyahi MTJ, Al-Musawi IHN and Abdel-Jabar BA 2018 High spectrum of PTEN gene mutation in Iraqi breast cancer patientsJ.Glob.Pharma.

Tech.10 242.

(14)

[28] Mutar MT, Goyani MS, Had AM and Mahmood AS 2019 Pattern of presentation of patients with breast cancer in Iraq in 2018: a cross-sectional studyJ. Global. Oncol. 16.

[29] Abdulwahid HM, Khalel EA andAlwan NAS 2019 Mammographic ,ultrasonographic and pathologic correlations of focal asymmetric breast densities among a sample of Iraqi womenJ.Contemp.Med.Sci., 5 131.

[30] Hiller SM, Mina A and Mina L 2016 Breast cancer risk factorIn:Mina LA, Storniolo AM, Kipfer HD, Hunter C andLud Ludwig KK Eds .Breast cancer prevention and treatment Springer, Switzerland 104.

[31] Grimsey E 2011An overview of the breast and breast cancerIn: Harmer V ed.Breast cancer nursing care and management.Second edition. Blackwell ,ltd.

[32] Lafta RK, Saeed EQ and Isa SA 2013 Risk factors of breast cancer among women (a sample from Baghdad) Iraqi J. Comm.Med. 11.

[33] Mohson KI, Khaleel IA and Riyadh B 2018 Ultrasound and mammographic findings of contra lateral breast in Iraqi patients underwent mastectomy for breast cancerI.O.S.R.- J.N.H.S. 7 68.

[34] Al-Alwan NAS, Al-Mallah NAG, Awn AK, Khalef T and Tariq S 2019 The actual practice of breast self-examination among sample of Iraqi patients with breast cancer. Al- Kindy Coll. Med. J. 15 28.

[35] Al-Gburi ASA and Alwan NAS 2019 Correlation between breast self examination practices and demographic characteristics,risk factors and clinical stage of breast cancer among Iraqi patients Maced.J.Med. Sci. 7 3217.

[36] Al-Awadi AF, Al-Nuaimi DS, Al-Naqqash MA and Alshewered AS 2020 Time to progression of early versus advanced breast cancer in Iraq Prensa Med. Argent106 1.

[37] Hatem SF, Alyaqubi KJ, Al-Atrooshi SAW, Alsayyid MM, Saad M and Safaa R 2016 The Study of HER-2/neu, ER/PR Expression Using Immunohistochemistry (IHC) in the Iraqi Breast CancerKufa J. Vet. Med. Sci. 7 18.

[38] Abood RA 2018 Breast cancer in Basra oncology center:aclinic-epidemiological analysisAsian Pac. J. Cancer Preven.19 2943.

[39] DeSantis C, Siegel R, Bandi P and Jemal A 2011 Breast cancer statistics, 2011.CA: A Cancer J. Clin.61 409.

[40] Bouchardy C, Fioretta G, Verkooijen HM, Vlastos G, Schaefer P, Delaloye JF,Neyroud- Caspar I, Balmer-Majno S, Wespi Y, Forni M, Chappuis P Sappino AP andRapiti E 2007 Recent increase of breast cancer incidence among women under the age of forty Br. J. Cancer 96 1743.

[41] Dobi A, Kelemen G, Kaizer L, Weiczner R, Thurzo L and Kahan Z 2011 Breast cancer under 40 years of age: increasing number and worse prognosisPathol. Oncol. Res. 17 425

[42] Hassan NH and Ali RM 2017 Determination of Contributing Environmental Factors to Breast Cancer in women: A Retrospective Study in Babylon GovernorateKerbala J.

Med.10 2687.

[43] Al-NaqqashMA 2009The Role of c-myc oncogene as aprognostic marker in breast cancer patients evaluated by immunohistochemistry and in situ hybridization MSc.

Thesis. College of Medicine. University of Baghdad, Iraq.

[44] Al-Rikabi NMJ 2015Immunohistological and Molecular Pathological markers of her- 2/neu Expression in Iraqi breast cancer Women patientsMSc.thesis . Collage of medicine /Sana’a University.

[45] Abdul Raheem FT 2005Breast Cancer in premenopausal women A thesis submitted to the Iraqi Board for Medical Specializations in Pathology.

[46] Matloob RS 2006HER-2/neu overexpression in breast cancer: Immunohistochemical StudyA thesis Submitted to the Iraqi Board for Medical specializations.

(15)

[47] Taucher S, Rudas M, Mader RM, Gnant M, Dubsky P, Bachleitner T andJakesz R 2003 Do we need HER‐2/neu testing for all patients with primary breast carcinoma?Cancer98 2547.

[48] Lester S, Weaver D, Morrow M, Cserni G and Tuzlali S 2012 Staging. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH and van de Vijer MJ World health organization classification of tumours of the breast.4th edition , International agency for research on cancer Lyon 20.22.

[49] Touma HS and Shani WS 2018 Increased transforming growth factor-β and interleukin- 17 transcripts in peripheral blood of breast cancer patients with different clinical stagesMed. J. Babylon15 145.

[50] Mohammed IK 2015Biomarkers in saliva and blood of breast cancer in women PhD.Thesis Al-Mustansiriyah University, College of science

[51] Alwan NAS 2018Tumor characteristics of female breast cancer : pathological review of mastectomy specimens belonging to Iraqi patients. World J. Breast Cancer Res. 1 1.

[52] Alwan NAS, Kerr D, Al-Okati A,Pezella F and Tawfeeq FN 2018 Comparative study on the clinicopathological profiles of breast cancer among Iraqi and British patientsOpen Public Health J. 11 177.

[53] Al-Musawi AAR 2018Immunogenetic Study of Iraqi women with Breast Cancer MSc.

thesis. university of Baghdad, College of education for pure science (Ibn-Al-Haitham) 113.

[54] Alwan NAS and Shawkat MM 2020 Treatment options and follow-up among Iraqi patients with breast carcinoma Europ. J. Med. Health Sci. 2 1.

[55] Khabaz MN 2014 Immunohistochemistry Subtypes(ER/PR/HER) of Breast Cancer:

Where Do We Stand in the West of Saudi ArabiaAsian Pac. J. Cancer Preven. 15 8395.

[56] Errahhali ME, Ouarzane M, El Harroudi T, Afqir S and Bellaoui M 2017 First report on molecular breast cancer subtypes and their clinico-pathological characteristics in Eastern Morocco: series of 2260 casesBMC women's Health17 1.

[57] Park EH, Min SY, Kim Z, Yoon CS, Jung KW, Aam SJ, Oh SJ, Lee S, Park BW, Lim W and HurMH 2017 Basic facts of breast cancer in Korea in 2014:the 10-year overall survival progressJ. Breast Cancer20 1.

[58] Alwan NAS, Tawfeeq FN and Mallah NAG 2019 Demographic and clinical profiles of female patients diagnosed with breast cancer in Iraq J.Contemp.Med.Sci. 5 14.

[59] Alwan NAS 2015 Family history among Iraqi patients diagnosed with breast cancer I.J.S.R. 6 869.

[60] Iqbal BM and Buch A 2020 Hormone receptor (ER,PR,HER2/neu) status and proliferation index marker (ki-67) in breast cancers: their onco-pathological correlation, short comings and future trendsMed.J. Dr.D. Y. Patil Univ. 9 674.