Histopathologic metrics of breast tumors in Northern Saudi Arabia

Abstract

The alarming liability of breast cancer, mainly among younger Saudi women, has been attributed to diverse factors requiring a manageable valuation. Therefore, this study aimed to assess the types of tumors and breast cancer presentation stages in Northern Saudi Arabia. In the present study, retrieved data regarding breast biopsies were received from the Department of Pathology at King Salman Hospital, Hail, Northern Saudi Arabia. Included data referring to breast cancer biopsies patients (including 131 females and two males) diagnosed during the period from November 2019 to November 2020. Out of the 133 patients, breast cancer was diagnosed in 49/133(36.8%) patients included 45/49(91.8%) invasive ductal carcinoma (IDC), 2/49(4.1%) invasive lobular carcinoma (ILC), and 2/49(4.1%) papillary carcinoma. The remaining 84 benign breast lesions included 40/84(47.6%) fibroadenoma, 11/84(13%) ductal hyperplasia, 9/84(10.7%) fibrocystic disease, 8/84(9.5%) adenosis, 4/84(4.8%) chronic mastitis, 3/84(3.6%) breast abscess & intraductal papilloma, 2/84(2.4%) duct ectasia & phylloides tumor, and 1/84(1.2%) lactating adenoma & lipoma. Breast cancer is highly prevalent in Northern Saudi Arabia with predominantly invasive ductal carcinoma. There is an increase in the incidence of younger patients with advanced stages of initial presentation. Fibroadenoma is the commonest benign breast lesion, followed by fibrocystic diseases in Northern Saudi Arabia.

KEYWORDS:

• Breast cancer
• ductal carcinoma
• fibroadenoma
• breast tumors
• Saudi Arabia

Introduction

Breast cancer is a leading cause of mortality in Saudi Arabia, and its incidence is rising in recent years, mimicking that occurring in western countries. The alarming burden of breast cancer, particularly among younger Saudi women, has been attributed to myriad factors that need close assessment (Almutlaq et al. 2017; Babiker et al. 2020). The low level of population awareness and absence of sustainable screening programs represent the significant drawbacks and obstacles in the control of breast cancer in Saudi Arabia (Elasbali et al. 2019; Alqahtani et al. 2020).

As breast cancer, education, and early detection campaigns can improve the ultimate breast cancer patient outcomes, implementing sustainable breast-self-examination, mammography, and clinical breast examination can reduce the disease's burden (Albeshan et al. 2020; Asiri et al. 2020).

High proportions of breast cancer cases with advanced stages of the disease with an increasing incidence among relatively younger patients are continuously being reported from Saudi Arabia (Ahmed et al. 2017). These may be attributed to the low utilization of open breast cancer screening services among wide-ranging Saudi women (Al-Hanawi et al. 2020).

Nevertheless, there is still a lack of data regarding breast cancer's pathogenesis in Saudi Arabia, in terms of histopathological patterns and other diagnostic measures concerning the patient's age. Thus, our objective in this investigation was to assess the types of tumors and breast cancer presentation stages in Northern Saudi Arabia.

Materials and methods

In the present study, retrieved data regarding breast biopsies were received from the Department of Pathology at King Salman Hospital, Hail, Northern Saudi Arabia. Included data referring to breast cancer biopsies patients (including 131 females and two males) diagnosed during the period from November 2019 to November 2020. The diagnosis of breast lesions was confirmed by conventional histopathology. The re-evaluation of the histopathological diagnosis of the tissue samples was done to verify the prior diagnosis and categorize the lesion's classification into benign and malignant types.

Statistical analysis

Retrieved information collections were entered through a computer software; Statistical Package for Social Sciences (SPSS version 16; SPSS Inc, Chicago, IL). Chi squire test was employed for statistical significance (P < 0.05 was considered significant).

Ethical consent

The protocol of this study was established agreeing with the 2013 Declaration of Helsinki and this study was approved by the ethics committee of the College of Medicine, University of Hail, Saudi Arabia. Ethical Committee approval number: EC00069.

Results

Within the period from October 2019 to October 2020, 133 patients attended our hospital with breast lesions. The patients aged 16–99 with a mean age ± Standard Deviation (Std) of 40.23 ± 15.35 years. The mean age for patients with breast cancer was 48.3 ± 13.3 years.

Out of the 133 patients, breast cancer was diagnosed in 49/133(36.8%) patients included 45/49(91.8%) invasive ductal carcinoma (IDC), 2/49(4.1%) invasive lobular carcinoma (ILC), and 2/49(4.1%) papillary carcinoma (see Figure 1). The remaining 84 benign breast lesions included 40/84(47.6%) fibroadenoma, (see Figure 2)11/84(13%) ductal hyperplasia, 9/84(10.7%) fibrocystic disease, 8/84(9.5%) adenosis, 4/84(4.8%) chronic mastitis, 3/84(3.6%) breast abscess & intraductal papilloma, 2/84(2.4%) duct ectasia & phylloides tumor, and 1/84(1.2%) lactating adenoma & lipoma, as indicated in Table 1, Figure 3. IDC cases were found in 6/32(19%) of the age group 25–34, and 10/33(%30.3) of the age group 35–44. The majority of fibroadenoma cases were seen in age <34 years 31/55(56.4%). Ductal hyperplasia, fibrocystic disease, and chronic mastitis were found predominantly in the age group 35–44 years, constituting 6/33(18%), 4/33(12%), and 3/33(9%), respectively. We saw all Intraductal Papilloma cases in the age group of 45–54 years 3/18(17%). All Phylloides tumor cases were seen in the age group of 25–34 years 2/32(6%), as shown in Table 1, Figure 3.

Figure 1. Breast ductal carcinoma (demonstrated by Hematoxylin and Eosin staining (X 100).

Figure 2. Breast fibroadenoma (demonstrated by Hematoxylin and Eosin staining (X 100).

Figure 3. Description of the patients by diagnosis and age.

Table 1. Distribution of the patients by diagnosis and age.

Diagnosis	<25 years	25–34	35–44	45–54	55+	Total
IDC	0	6	10	10	19	45
ILC	0	0	1	0	1	2
Papillary carcinoma	0	1	0	0	1	2
Fibroadenoma	16	15	4	2	3	40
Ductal hyperplasia	2	0	6	2	1	11
Fibrocystic disease	2	3	4	0	0	9
Adenosis	3	2	2	0	1	8
Chronic mastitis	0	0	3	1	0	4
Breast abscess	0	1	2	0	0	3
Intraductal papilloma	0	0	0	3	0	3
Duct ectasia	0	0	1	0	1	2
Phyllodes tumor	0	2	0	0	0	2
Lactating adenoma	0	1	0	0	0	1
Lipoma	0	1	0	0	0	1
Total	23	32	33	18	27	133

About 28/45(62.2%) of the IDC presented on the left side. All of the papillary carcinoma presented on the left side of 2/2(100%). Around 16/49(32.7%) presented with lesion size >2 cm. For quadrant diagnosis, upper outer, retro-areolar, lower outer, lower inner, and upper inner were identified in 16(46%), 8(23%), 4(11%), 3(9%), and 4(11%) of IDC, in that order. According to the Bi-Rad score, 21/33(63.7%) were scored 4, and 11/33(33.3%) were scored 5, and only 1/33(3%) score 1, as indicated in Table 2.

Table 2. Distribution of breast cancer by clinical presentation measures.

Category	IDC	ILC	Papillary carcinoma	Total
Lesion site
Right	16	1	0	17
Left	28	1	2	31
Bilateral	1	0	0	1
Size
≤2 cm	20	0	1	21
>2 cm	16	2	1	19
Quadrant diagnosis
Upper outer	16	2	1	19
Retro-areolar	8	0	1	9
Lower outer	4	0	0	4
Lower inner	3	0	0	3
Upper inner	4	0	0	4
Bi-Rad score
Score 3	1	0	0	1
Score 4	19	1	1	21
Score 5	10	0	1	11

Positive lymph nodes were identified in 24/49(50%) cases, including 22/45(49%) IDC and 2/2(100%) ILC. The majority of patients were identified in grade 2, representing 41/47(87%). The most frequent subtypes were luminal A, followed by luminal B, Triple-negative, and Her2-enriched, constituting 14/32(44%), 7/32(22%), 6/32(19%), and 5/32(15%), correspondingly, as indicated in Table 3.

Table 3. Distribution of breast cancer by histopathological measures.

Category	IDC	ILC	Papillary carcinoma	Total
Lymph node
Positive	22	2	0	24
Negative	23	0	2
Provisional Grade
Grade 1	3	0	1	4
Grade 2	39	2	0	41
Grade 3	2	0	0	2
Subtype
Luminal A	12	1	1	14
Luminal B	7	0	0	7
Her2-enriched	5	0	0	5
Triple-negative	6	0	0	6

Table 4, Figure 4 summarized the distribution of the patients’ diagnostic parameters by age. About 19 patients presented with lesion size >2 cm, 7/19(37%), 5/19(26%), and 4/19(21%) were in the age ranges 55+, 35-44, and 25–34 years, respectively. For quadrant, the upper outer is more frequent in 55+ years 8/19(42%), and 35–44 years 6/19(32%). Retro-areolar were seen in 55+ years 4/9(44.4%), and 25–34 years 3/9(33.3%).

Figure 4. The patients’ diagnostic parameters by age.

Table 4. Distribution of the patients’ diagnostic parameters by age.

Category	25–34 years (n = 32)	35–44 (n = 33)	45–54 (n = 18)	55+ (n = 27)	Total
Lesion Size
≤2 cm	3	5	2	11	21
>2 cm	4	5	3	7	19
Quadrant diagnosis
Upper outer	2	6	3	8	19
Retro-areolar	3	1	1	4	9
Lower outer	0	1	2	1	4
Lower inner	1	0	1	1	3
Upper inner	1	1	0	2	4
Bi-Rad score
Score 3	0	1	0	0	1
Score 4	2	5	5	9	21
Score 5	3	2	2	4	11
Lymph node
Positive	3	6	4	11	24
Provisional Grade
Grade 1	1	1	0	2	4
Grade 2	5	10	8	18	41
Grade 3	1	0	1	0	2
Subtype
Luminal A	1	5	1	7	14
Luminal B	1	3	2	1	7
Her2-enriched	0	0	3	2	5
Triple-negative	2	1	1	2	6

For the Bi-Rad score, the most frequent score was 3, seen in 55+ years 9/21(43%), and 35–54 years 10/21(47.6%). Positive lymph nodes were frequently seen in 55+ years 11/24(46%), and 35–44 years 6/24(25%). Provisional Grade, Grade 2, the most common frequently seen in 55+ years 18/41(44%), 35–44 years 10/41(24%), and 45–54 years 8/41(20%). For subtypes, Luminal A was frequently seen in 55+ years 7/14(50%), and 35–44 years 5/14(36%). Luminal B was seen in 35–44 years 3/7(43%). Her2-enriched was seen in 45–54 years 3/5(60%). Triple-negative (TN) is frequently seen in 55+ years & 25–34 years, representing 2/6(33.3%). About 4/6(67%) TN were associated with BI-RAD 4.

Discussion

In this study, we reviewed one year series of patients who were admitted to our hospital with breast tumors. The overall incidence rate of all breast cancers among breast tumors was 36.8% (35.3% in females and 1.5% in males), including 33.8% for invasive ductal carcinoma, 1.5% for invasive lobular, and 1.5% for papillary carcinoma. These findings showed higher incidence rates than the early reported incidence rate of 27.4% in females (Saggu et al. 2015). During the period from 1990 to 2016, breast cancer incidence increased 10-fold (Althubiti and Nour Eldein 2018). However, the overall reported incidence of breast cancer in Saudi Arabia (in 2018) was 14.8%, with a mortality rate of 8.5% (Saudi Arabia. Most common cancer cases 2018). The incidence rates of IDC, ILC, and papillary carcinoma of all female breast cancer were 91.4%, 4.3%, and 4.3%, respectively. Relatively slight lower incidence rates were previously reported in Saudi Arabia, including 81.8% for ductal carcinoma and 3.4% for lobular carcinoma (Asiri et al. 2020).

In the present study, the mean age for patients with breast cancer was 48.3 ± 13.3 years. This is relatively lower than all of the previous reports from Saudi Arabia (Alabdulkarim et al. 2018; Asiri et al. 2020), which indicates the increased incidence of breast cancer among somewhat younger females.

Most patients attended with left side lesions 63.3% in the present study, and upper outer quadrant 38.8%. It was reported that breast cancer is more likely to occur on the left side, except for specific histopathological patterns (Cheng et al. 2018). Radiotherapy for the left side breast was reported to influence the heart and increase fatality (Hashiguchi et al. 2020). The predominant of the upper outer quadrant supports most of the studies in this context (Burrah et al. 2020).

In the current study, the Bi-RAD score4 was the most frequent, 63.6%, followed by Score5, constituting 33.3% of the cases. BI-RAD scores 4& 5 are potentially valuable for the prediction of breast cancer (Luo et al. 2019). However, it was reported that patients with BI-RAD 4 are more likely to have triple-negative carcinoma than BI-RADS 5 (Oktay et al. 2014), which was consistent with our findings in the present study (67%).

Approximately 49% of the patients in this series were identified with a positive lymph node. Positive lymph nodes, which indicate breast cancer metastasis and late diagnosis, usually affect the overall patient’s management in terms of staging, treatment, and subsequent survival (Marino et al. 2020). The high proportions of patients presenting positive lymph nodes designate the lack of early detection programs resulting in patients presenting with advanced disease stages. Moreover, 87.2% of the patients in this study showed stage II breast cancer, and 4.3% with stage III. Better survival is usually associated with a lower stage of presentation, which reverses our findings, indicating later detection (Yang et al. 2019) inconsistent with Arabian countries’ reports, including Saudi Arabia (Al-Thoubaity 2020; Tanner and Cheung 2020).

In the present study, the most common breast cancer subtype was Luminal A (43.8%), followed by Luminal B (21.9%), Triple-negative (18.8%), and Her2 (15.6%). A recent study from Saudi Arabia with relatively few varying proportions included 58.5% for Luminal A, 14% for Luminal B, 16% for Triple-negative, and 11.4% for Her2 (Al-Thoubaity 2020).

On the other hand, several benign breast lesions were identified in the present series of patients with the most frequent fibroadenoma (30%&47.6%) of (all breast lesions & benign breast lesions) followed by Ductal hyperplasia (8.3%&13%) and fibrocystic disease (6.8%&10.7%), in that order. It was reported that fibroadenoma represents 44–94% of the breast biopsied lesions and 68% of all breast masses (Lee and Soltanian 2015). A study from Saudi Arabia reported incidence rates of 44.3% for fibroadenoma and 23.4% for fibrocystic disease (Albasri 2014). Another study from Northern Saudi Arabia has reported a prevalence of 64.6% for fibroadenoma (Ahmed et al. 2017). However, diverse epidemiological values have been reported from Saudi Arabia with different benign and malignant lesions (Bosaeed et al. 2018).

Nevertheless, several modifiable risk factors may play roles in the etiology of breast cancer in Saudi Arabia. In recent years there were increasing incidence rates of obesity and type II diabetes mellitus and thyroid disease in Saudi Arabia (Ahmed et al. 2014; Alzahrani et al. 2017; Al-Zahrani et al. 2019), due to fast changing in the lifestyle. Other factors such as BRCA1 and BRCA2 gene mutations are still unknown. However, there is ongoing Saudi human genome project, which is including the study of several breast cancer related genes including BRCA genes.

Conclusion

Breast cancer is highly prevalent in Northern Saudi Arabia with predominantly invasive ductal carcinoma. There is an increase in the incidence of younger patients with advanced stages of initial presentation. Fibroadenoma is the most joint benign breast lesion, followed by fibrocystic diseases in Northern Saudi Arabia.

Acknowledgements

The authors would like to thank people at the Department of Pathology, King Salama Hospital Ha'il, for their assistance in sample collection.

Authors contribution

HGA: Conception, administration, analysis, drafting, and approval of the final version; KKA: Conception, design, data acquisition, practical part, approval of the final version; HMA: Conception, analysis, drafting, practical part, approval of the final version; ABE: Conception, design, data acquisition, approval of the final version; AMAA: Conception, analysis, drafting, and approval of the final version; AOH: Conception, analysis, drafting, and approval of the final version; IAG: Conception, analysis, drafting, and approval of the final version; AME: Consultation, analysis, drafting, and approval of the final version.; HS: Conception, analysis, drafting, and approval of the final version.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, [HGA]. The data are not publicly available due to [restrictions e.g. their containing information that could compromise the privacy of research participants].

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research has been funded by Scientific Research Deanship at the University of Ha'il – Saudi Arabia, through project number RG-20 009.