|Original Research (Original Article)|
Norah Alotaibi et al, 2019;3(8):716–725.
International Journal of Medicine in Developing Countries
Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia
Norah Alotaibi1*, Razan Alosaimy1, Wedyan Al-Mushaddak1, Manahil Nouri2
Correspondence to: Norah Alotaibi
*Joint Program of Family Medicine, Jeddah, Saudi Arabia.
Email: dr-nora101 [at] hotmail.com
Full list of author information is available at the end of the article.
Received: 11 April 2019 | Accepted: 23 April 2019
© 2019 IJMDC. Published by Discover STM Publishing Ltd.
Breast cancer ranks second most commonly diagnosed cancer worldwide, with approximately 12% among all the cancers, while in women it stands as the most prevalent cancer in 154 countries and the leading cause of cancer death in 103 countries. The stage of breast cancer at diagnosis is an outstanding prognostic factor of treatment efficacy and survival, as well as a determinant factor of local and metastatic recurrence. Advanced-stage breast cancer (AS-BC) is associated with lower survival rates compared to early diagnosed cases. The present study aimed at estimating the prevalence of AS-BC among newly diagnosed female subjects and to identify the associated factors and predictors of the disease.
A retrospective chart review was conducted in three tertiary hospitals in Jeddah, Saudi Arabia, including patients with breast cancer, who were diagnosed and followed up in the participating centers during the period October 2013–October 2018. Data were collected in a standardized fashion using a semi-structured datasheet.
A total of 824 women were included in the study. Furthermore, AS-BC rate was found lower among patients with a family history of breast cancer and or personal history of benign breast disease, while it was higher among those with a history of exposure to ionization radiation or other comorbidities, notably diabetes and hypertension. Significant lifestyle factors included a sedentary lifestyle, higher weight, and body mass index. Among all the statistically significant factors, educational level [postgraduate, odds ratio (OR) = 0.17, p = 0.006] and exposure to ionization radiation (OR = 2.50, p < 0.001) were the only independent factors of AS-BC.
Advanced-stage accounts for two-thirds of the primary breast cancer cases, which is remarkably higher than the reported international literature and contrasting with the locally implemented screening and prevention programs. The identification of socioeconomic factors of AS-BC should guide the adaptation of care offered and communication strategies in order to improve the attendance to systematic screening programs among the most deprived groups.
Breast cancer, advanced stage, late diagnosis, screening, prevention.
According to recent global statistics, breast cancer ranks second most commonly diagnosed cancer worldwide, with approximately 12% among all the cancers, while in women it stands as the most prevalent cancer in 154 countries and the leading cause of cancer death in 103 countries [1–3]. In 2018, over 2 million cases were newly diagnosed, and up to 627,000 deaths were recorded, signifying disturbing rates of incidence (30–113) and mortality (8.6–25.5) per 100,000 female, depending on the region and or country [1,2,4]. The stage of breast cancer at diagnosis is an outstanding prognostic factor of treatment efficacy and survival, as well as a determinant factor of local and metastatic recurrence . Advanced-stage breast cancer (AS-BC), defined as Tumor, Nodes, Metastases (TNM) classification of malignant tumors stage III or IV at diagnosis, is associated with lower survival rates compared to early diagnosed cases. Data from Europe show up to 47% decrease in 1-year survival and 73% decrease in 3-year survival in stage IV disease, by reference to stage I–II. Data from Saudi Arabia showed a 20% drop in 10-year survival rate from stages I and II to stage III along with a 39-year decline in median survival . Moreover, the clinical significance of AS-BC involves greater morbidity with the persistence of devastating symptoms, which are not only due to the disease invasiveness but also to more aggressive therapeutic protocols and their burdensome side effects. Consequently, health-related quality of life is considerably affected among patients with AS-BC . International reports showed relatively low rates of AS-BC at diagnosis in the developed countries, ranging between 8.3% and 23.5% in Europe, 19.7% in New Zealand, and 0%–20.1% in Canada and the United States [6,8–10]. These discrepant figures in early versus late stage rates at diagnosis account for the variability in breast cancer-related mortality between the developed countries . Therefore, considerable efforts are exerted to prompt early diagnosis, using active screening programs and the use of state-of-art imaging and other diagnostic methods, besides the implementation of specialized facilities and centers [11–14]. In Saudi Arabia, official statistics by the Ministry of Health and other local reports agree in the fact that breast cancer is the first national cancer, with approximately 20% of newly diagnosed cases and a constantly increasing incidence; and affects relatively younger patients compared to the developed countries [15–18]. However, data on stage at diagnosis and determinants of AS-BC are scarce, and the few local and regional studies, yet outdated, showed high rates of AS-BC (up to 68%) with 11%–15% of patients being diagnosed at stage IV [19–22]. These figures are combined with low awareness level among the local population, resulting in low attendance to screening clinics and underuse of the available, and specialized health resources . Thus, by conducting this study, we aimed to provide insight into the clinical and histopathological patterns of breast cancer in the western region of Saudi Arabia by estimating the prevalence of AS-BC at diagnosis and investigating the associated factors and predictors. Such data would provide valuable local indicators for awareness and screening programs and could represent an updated reference line for eventual interventional programs.
Subjects and Methods
A retrospective chart review study was conducted in three tertiary hospitals in Jeddah, Saudi Arabia, including King Abdulaziz University Hospital (KAUH), King Abdulaziz Hospital, and King Abdullah Medical City, Jeddah, Saudi Arabia. All the patients with breast cancer, who were diagnosed and followed up in the participating centers during the period of October 2013 and October 2018, were included. Ethical clearance was obtained from the Directorate of Health Affairs, Ministry of Health, Jeddah, as well as from the institutional review boards of the participating tertiary care centers. Written permissions from all the hospitals directors and relevant authorities were obtained before conducting the data collection. Sample size (N = 382) was calculated to detect 35%–54% of cases with advanced stage breast cancer (stage III or more) at diagnosis, with 95% confidence interval, 80% statistical power and 0.05 margin error. The percentage interval (35%–54%) was consistent with data from Ezzat et al.  (King Faisal Specialist Hospital and Research Center) and that from El Saghir et al.  (Arab countries), as well as with results from our pilot study conducted at KAUH and including 156 cases, which showed 53.7% of advanced stage cases. The sample size was increased by two-fold to compensate for eventual incomplete files, resulting in a target sample size N = 764. In each participating center, a complete list of patients’ records was constructed and ordered by hospitalization number, a systematic random sampling was used to select each third file from a random starting point. Data were collected in a standardized fashion using a semi-structured datasheet that was developed based on the major factors of breast cancer and AS-BC reported in the literature and was validated by three consultants. It was divided into five parts: (1) Sociodemographic data including age at diagnosis, marital status, educational level, etc.; (2) Reproductive factors including age at menarche, parity, miscarriages, breastfeeding, menopausal status, used of hormone therapy, etc.; (3) Family and personal history including history of breast cancer in first, second, and third degree relatives, personal breast history (cancer, benign diseases, biopsy) and other medical history, etc.; (4) Lifestyle and clinical factors including physical activity level, smoking status, weight and height, etc.; and (5) Pathological presentation including tumor gross, microscopic histochemical features, such as side (left, right or bilateral), size, local invasiveness, grade, histological subtype (ductal, lobular, etc.), hormonal status [estrogen, progesterone and human epidermal growth factor 2 (HER2) receptors], pathological stage at diagnosis and architectural features (comedo, papillary, micropapillary, etc.). The study primary outcome was advanced-stage breast cancer at diagnosis, which was defined as all stage III and IV diseases.
Statistical analysis was performed with the Statistical Package for Social Sciences version 21.0 for Windows (SPSS Inc., Chicago, IL). The prevalence of advanced-stage was calculated as the percentage of patients that were classified as stage IIIA, IIIB, or IV at diagnosis among the total population, and was presented with a 95% confidence interval. Descriptive statistics were used to present all factors’ data; categorical variables were presented as frequency and percentage, while numerical variables were presented as mean ± standard deviation (SD). Analysis of factors associated with advanced-stage used chi-square test or Fisher’s exact test for categorical variables, as appropriate and independent t-test for numerical variables. Multivariate binary logistic regression was carried out to analyze independent risk factors of advanced-stage; different models were tested including various sets of clinically and statistically significant factors. Results were presented as odds ratio (OR) with 95% class interval (CI). A p value of <0.05 was considered to reject the null hypothesis.
A total of 824 women with breast cancer was diagnosed and followed up between the study period; mean (SD) age was found to be 53.06 (11.91) years, 68.1% married and 32.8% had university-level education. Mean (SD) age at menarche and mean (SD) age at first childbirth was 11.41 (1.26) years and 19.49 (4.01) years, respectively, and 72.1% had four children or more. The majority (77.9%) of participants had ever used contraceptives, including oral (71.5%), intra-uterine device (22.1%), and injections (3.4%). Regarding menopausal status, 12.3% were in perimenopause and 62.1% were menopaused with mean (SD) menopausal age = 49.84 (0.95) years. The family history of breast cancer was found among 27.9% of the participants. Personal breast history showed a previous malignant tumor (6.6%), benign disease (12.7%), and biopsy (13.7%). Other personal history showed the prevalence of exposure to ionization radiation (77.2%), hysterectomy (0.7%), and other systemic comorbidities (58.1%), including diabetes (28.5%), hypertension (20.6%), and dysthyroidism (3.5%). The percentage of smoking was relatively high including current (10.2%), past (10.3%) and passive (10.7%) smoking, while the level of physical activity was low with 5.6% practicing regular exercise. In 57.0% cases, BC was located in the left breast, while it was bilateral in 0.6%. Mean (SD) tumor size was 2.93 (1.60) cm, with a high rate of local invasiveness (90.7%) and lymph node involvement (85.7%), resulting in 65.1% and 22.7% of tumors classified as grades 2 and 3, respectively. The most frequent histological type was ductal (86.8%) followed by lobular (10.2%), and tumor cells were positive to estrogen, progesterone and HER2 receptors in 80.4%, 76.0%, and 28.4% of the cases, respectively. The prevalence of advanced-stage BC (stage IIIA or higher) was 67.8% (95% CI = 64.4%, 71.0%). The most frequently observed tumor architecture was solid (68.5%), followed by comedo (27.1%) and cribriform (9.1%). Regarding the treatment, the majority of patients underwent mastectomy (69.1%), while 28.1% underwent lumpectomy (Table 1).
Advanced-stage breast cancer was associated with older age [mean (SD) = 54.80 (11.86) versus 49.25 (11.18) years, p < 0.001] and younger age at first childbirth [18.97 (3.27) versus 20.77 (5.06) years, p < 0.001] compared to an early stage, respectively. Additionally, it was also more prevalent among widowed (81.2%) than other marital status (p = 0.001), and among less-educated (72.6% of illiterate, 79.0% of primary school level, and 71.2%) than highly educated (59.8% among university-level and 25.0% among postgraduates; p < 0.001). Furthermore, it was associated with high parity (p = 0.001), long breastfeeding duration (p < 0.001), and menopause (p < 0.001) (Table 2).
Advanced-stage BC was less prevalent among patients with family history of BC (62.8% versus 70.1%, p = 0.040) and those who have personal history of benign breast disease (60.4% versus 70.1%, p = 0.050); while it was more prevalent among those with history of exposure to ionization radiation (72.9% versus 49.2%, p < 0.001), other comorbidities (73.4% versus 60.1%, p < 0.001) notably diabetes (75.5% versus 64.7%, p = 0.003) and hypertension (75.4% versus 65.8%, p = 0.017). Regarding lifestyle factors, regular exercise was associated with lower prevalence of advanced-stage BC (50.0%) by reference to sedentary lifestyle (74.3%) and irregular activity (56.2%), and the difference is statistically significant (p < 0.001). Furthermore, advanced-stage was associated with higher weight [mean (SD) = 80.80 (37.65) versus 73.71 (15.00) kg, p = 0.003] and body mass index (BMI) [mean (SD) = 30.45 (5.38) versus 29.31 (8.51 kg/m2, p = 0.020] compared to early stage (Table 3).
Advanced-stage was characterized by greater tumor size [mean (SD) = 3.40 (1.54) versus 1.95 (1.23) cm, p < 0.001] and was associated with ductal subtype (71.3%) compared to lobular (48.2%) and other subtypes (30.8%) and the difference was statistically significant (p < 0.001). Positive HER2 receptor was associated with a lower prevalence of advanced-stage (56.0% versus 72.6%, p < 0.001). Furthermore, presence of comedo (80.1% versus 67.5%, p = 0.001) and solid (75.7% versus 54.7%, p < 0.001) components were associated with a higher percentage of advanced-stage cases (Table 4).
Among all statistically significant factors, high educational level (postgraduate, OR = 0.17, p = 0.006) and exposure to ionization radiation (OR = 2.50, p < 0.001) were the only independent risk factors of advanced-stage breast cancer (Table 5).
Review of literature shows that the rate of AS-BC in the present study is remarkably greater than that observed in the developed countries, and matches the highest end of rates reported in the Arab countries. In Europe, the percentage of AS-BC (stage III + IV) cases was 8.3% (5.3% + 3%) in Sweden, 9% (4% + 5%) in Germany, 9.5% and (3.8% + 5.7%) in Norway, 14.6% (9.2% + 5.4%) in the UK, and 23.5% (15.8% + 7.7%) in Denmark; while in Canada, it was 20.9% (13.3% + 7.6%), respectively [6,8]. Other data from a CONCORD high-resolution study, including seven United States (US) states and 12 European countries, showed that the prevalence of locally-advanced disease (T4, any N, M0) ranged between 0% and 28% with higher rates in Europe, especially Denmark, Estonia, and Sweden compared to the US; however, node-positive tumors ranged between 22% and 44%, while the rate of metastasis ranged between 2% and 19% . Regionally, the prevalence of AS-BC in Arab countries was generally lower than that reported in the present study, with 32.5% of cases in Bahrain, 35% in Palestine, 50.7% in Oman; whereas Egypt totalized the highest rates with 68%, thus matching our findings . More disturbing, lesser rates of AS-BC are found in the eastern province of Saudi Arabia, according to the previous study by Ibrahim et al. , who reported 46% of cases with AS-BC including stage III (30%) and stage IV (16%). These observations raise the alarm bells over a possibly increasing prevalence of AS-BC, probably in relation with the global increase in breast cancer incidence, but also to some eventual multifactorial context impeding the efficacy of and adherence to screening programs. Nevertheless, comparison of our findings with the previous data should be done with caution by consideration of eventual differences in the method of participants’ recruitment and the levels of implementation of screening programs that may vary across regions and over the years. Findings of the present study highlighted the significance of sociodemographic status in the timing of the patient’s presentation for diagnosis; with the educational level being the most significant predictor. The educational level represents a key determinant for the ability of the patient to recognizing abnormal symptoms, seeking care, adhering to screening programs, and getting informed, all being potential factors of early versus delay in diagnosis . Furthermore, it has been demonstrated that women living in disadvantaged areas, by regards to educational and economic status, had up to 75% risk of presenting with AS-BC . In the present study, older age, widowed status, and being menopaused were found to be statistically associated with AS-BC but not independent risk factors; which demonstrate that these factors are probably confounded with educational status, is all dependent on age, while older generations have generally lower educational level. Other socio-demographic factors have been reported as factors of AS-BC in other studies. In the US, ethnicity represented one of the risk factors of presenting with AS-BD, which was reflected in inter-ethnic discrepancies in treatment options and outcomes notably in mortality . More recently in Norway, patients from Asian and African descents had greater proportions of AS-BC compared to native Norwegians, along with significant differences in age at diagnosis and outcomes . Comparable findings were reported in New Zealand, between Maori and European descents . These findings reveal the significant contribution of socio-demographic and cultural factors in hindering detection of breast cancer at an early stage, probably impacting several patient-related care aspects such as level of awareness, attitude regarding screening, care-seeking behavior, treatment compliance, etc.; besides being generally associated to detrimental lifestyle factors. Another critical socio-demographic factor that has not been investigated in the present study is the accessibility of care and distance to facilities. It has been demonstrated that longer home-care facility travel distance was associated with up to 50% greater risk for presenting with AS-BC .
Table 1. Pathological presentation (eight cases without pathological presentation were excluded, N = 816).
Table 2. Demographic and reproductive factors associated with advanced stage breast cancer at diagnosis (N = 816).
MHT, menopause hormone therapy.
Table 3. Medical history and lifestyle factors associated with advanced-stage breast cancer.
Table 4. Pathological presentation factors associated with advanced stage breast cancer.
Table 5. Independent risk factors of advanced-stage breast cancer (binary logistic regression).
Dependent variable: advanced-stage breast cancer at diagnosis. CI, confidence interval; ref, reference category;
*statistically significant result (p < 0.05).
The combination of all these socioeconomic factors suggests the existence of different levels of risk among the population, which would be interesting, yet crucial, to identify locally. Care policies and guidelines should be established based on this risk stratification to adapt both care offer and actions, including health education and preventive and screening programs, to each target risk-group. Other factors that were remarkably associated with lesser rates of AS-BC were a positive family history of breast cancer and a personal history of benign breast disease. Although neither of these factors was demonstrated to be an independent factor, they are probably indicative of the level of awareness, which emphasizes the relevance of awareness-raising campaigns . The disease stage at diagnosed is strongly predicted by attendance to the screening program, which is proposed as a key measure to prompt early detection of breast cancer. It was previously reported that the prevalence of AS-DC was two-to-three times lower among patients who were diagnosed via screening programs than those who were diagnosed via another pathway . In Saudi Arabia, low levels of attendance to screening clinics are reported, contrasting with the improved availability of and accessibility to specialized facilities and the implemented policies and systematic screening programs . This furthers the significance of measuring the incidence and prevalence of AS-BC to monitor the effectiveness of breast cancer prevention and screening programs, as well as the targeted education and awareness raising campaigns. The most notable limitation of this study was the failure to investigate some key factors and determinants of AS-BC. Among these factors includes the diagnostic pathways, i.e., whether patients were diagnosed via screening program versus non-screened, which would provide valuable indications on the level of implementation and efficacy of screening in detecting early-stage disease; however, such data was missing from the patients’ records. Another limitation of the present study was the absence of exploration of the outcomes by disease stage, which would emphasize the importance of screening and early diagnosis.
Advanced-stage accounts for two-thirds of the primary breast cancer cases among adult women in western Saudi Arabia, which is remarkably higher than in international literature and contrasting with the locally implemented screening and prevention programs. Several socio-demographic and clinical factors are associated with advanced-stage at diagnosis, of which the educational level was the most significant predictor, indicating the urgent need for proficient education and awareness raising campaigns. The identification of all socioeconomic factors of AS-BC may enable risk stratification among the target population to adapt care offer and communication strategies in order to improve the attendance to systematic screening programs among the most deprived groups. Furthermore, findings of this study highlight the significance of measuring the rates of AS-BC, besides mortality, to monitor the effectiveness of such programs both at the national and health sector levels.
List of Abbreviations
Conflict of interest
The authors declare that there is no conflict of interest regarding the publication of this article.
Consent for publication
Informed consent was obtained from all the participants.
The ethical approval was granted by Biomedical Ethicsn Research Committee at Faculty of Medicine, King Abdulaziz University, vie ref # 537-18.
Norah Alotaibi1, Razan Alosaimy1, Wedyan Al-Mushaddak1, Manahil Nouri2
|How to Cite this Article|
Alotaibi N, Alosaimy R, Al-Mushaddak W, Nouri M. Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia. IJMDC. 2019; 3(8): 716-725. doi:10.24911/IJMDC.51-1555003245
Alotaibi N, Alosaimy R, Al-Mushaddak W, Nouri M. Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia. http://www.ijmdc.com/?mno=43036 [Access: September 23, 2019]. doi:10.24911/IJMDC.51-1555003245
AMA (American Medical Association) Style
Alotaibi N, Alosaimy R, Al-Mushaddak W, Nouri M. Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia. IJMDC. 2019; 3(8): 716-725. doi:10.24911/IJMDC.51-1555003245
Alotaibi N, Alosaimy R, Al-Mushaddak W, Nouri M. Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia. IJMDC. (2019), [cited September 23, 2019]; 3(8): 716-725. doi:10.24911/IJMDC.51-1555003245
Alotaibi, N., Alosaimy, . R., Al-Mushaddak, . W. & Nouri, . M. (2019) Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia. IJMDC, 3 (8), 716-725. doi:10.24911/IJMDC.51-1555003245
Alotaibi, Norah, Razan Alosaimy, Wedyan Al-Mushaddak, and Manahil Nouri. 2019. Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia. International Journal of Medicine in Developing Countries, 3 (8), 716-725. doi:10.24911/IJMDC.51-1555003245
Alotaibi, Norah, Razan Alosaimy, Wedyan Al-Mushaddak, and Manahil Nouri. "Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia." International Journal of Medicine in Developing Countries 3 (2019), 716-725. doi:10.24911/IJMDC.51-1555003245
MLA (The Modern Language Association) Style
Alotaibi, Norah, Razan Alosaimy, Wedyan Al-Mushaddak, and Manahil Nouri. "Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia." International Journal of Medicine in Developing Countries 3.8 (2019), 716-725. Print. doi:10.24911/IJMDC.51-1555003245
APA (American Psychological Association) Style
Alotaibi, N., Alosaimy, . R., Al-Mushaddak, . W. & Nouri, . M. (2019) Prevalence and determinants of advanced-stage breast cancer in Jeddah tertiary hospitals, Saudi Arabia. International Journal of Medicine in Developing Countries, 3 (8), 716-725. doi:10.24911/IJMDC.51-1555003245