Prof. Worku, Alemayehu (PhD)Dr.Addissie, Adamu (PhD)Dr.Assefa, Mathewos(MD, Oncologist)Dr. Jemal, Ahmedin(PhD)Abraha, Alem Gebremariam(PhD)2021-07-042023-11-052021-07-042023-11-052021-05http://etd.aau.edu.et/handle/123456789/27049Background: Breast cancer is a leading cancer among women in Ethiopia. It accounts for onethird of all newly diagnosed female cancers. Most women with breast cancer in Ethiopia are diagnosed with late-stage disease, do not receive high-quality care, and face a poor prognosis. Locally relevant information on the extent of delayed diagnosis, reasons for late diagnosis, care, and determinants of survival among women with breast cancer is essential to guide clinical practices and public health policy. However, little is known about the extent and reasons for patient interval (from date of symptom recognition to the first consultation of health care providers), diagnosis interval (from consultation to diagnosis), and treatment initiation interval (from diagnosis to treatment initiation). Moreover, evidence on the relationship between patient delay (> 90 days)/diagnosis delay (> 30 days) and stage at diagnosis, and its effect on survival among women with breast cancer in Ethiopia is limited. Objectives: To determine the magnitude of delays (patient and diagnosis delay) as well as stage at diagnosis and its effects on the survival of women with breast cancer in Addis Ababa. Methods: The study employed mixed-methods (a cross-sectional study, a qualitative study, and a prospective cohort study). A cohort of 441 women newly diagnosed with breast cancer between 1 st of January 2017 to 30 th of June 2018 in Addis Ababa were recruited for the quantitative phase of the study, and followed prospectively for two years. Data were collected at different points in time, as a cross-sectional study (Paper I and III) and prospective cohort study design (Paper IV) to address the quantitative study objectives. During recruitment, data on the participants' socio-demographic characteristics, date of first symptom recognition, and medical consultation after recognizing symptoms were collected using a structured interviewer-administered questionnaire. The date of diagnosis was taken from the patient's pathology report. One year after the recruitment, medical data, such as stage at diagnosis, date of diagnosis, histologic tumor type, date of receipt of treatment, and type were captured using a data extraction tool from the study participants’ medical charts. Finally, at about two years following diagnosis, data related to survival status were obtained using both face-toface interviews and telephone interviews. Also, medical charts were reviewed to update the treatment status of the study participants. We have conducted a univariable descriptive analysis to describe each variable. Multivariable Poisson regression with a robust variance model was used to determine the factors associated with patient/diagnosis delay and stage at diagnosis. Also, Kaplan-Meier and multivariable Cox regressions were used to determine the overall survival rate and factors contributing to the overall survival of women with breast cancer, respectively. All statistical tests were assessed for significance at p-value < 0.05. The qualitative study (Paper II) was conducted to explore the patients’, family members’, and health care providers’ perspective on late diagnosis of breast cancer. It was employed among purposively selected 23 in-depth interviewees. Each of the audio recordings was transcribed verbatim, coded, and analyzed using thematic analysis. Results: The magnitude of patient (>90 days) and diagnostic delays (>30 days) was 35.7%, 95% CI (31.1%, 40.3%) and 69.1%, 95% CI (64.6%, 73.3%), respectively. Patient delay was significantly higher among women who used traditional medicine before consultation (adjusted prevalence ratio [aPR] =2.13, 95% CI (1.68, 2.71). Diagnosis delay was significantly higher among women whose first consultation was at health centers (aPR=1.19, 95% CI [1.02, 1.39]) and those visited ≥ 4 facilities before confirmation (aPR=1.24, 95% CI [1.10, 1.40]) but lower among women who recognized progression of symptoms before consultation (aPR=0.73, 95% CI (0.60, 0.90). The qualitative study revealed that pre-diagnostic awareness about breast cancer risk, causes, initial symptoms, early detection methods, and treatment was low. Disregarding the clinical importance of the first symptom or seeking care from traditional healers were noted as common practices among women with breast cancer that contributed to late diagnoses. Also, lack of awareness, and misperception about breast cancer treatment and its outcomes, competing priorities, financial insecurity, fear of diagnosis of cancer, and weak health systems (e.g., delay in referral and long waiting period for consultation) were identified as important causes of late diagnosis of women with breast cancer. The median (interquartile range [IQR]) tumor size at diagnosis was 4 (3 to 6) centimeters. Sixtyfour percent of the women (95% CI [59.5%, 68.8%]) were diagnosed at advanced-stages (44% stage III and 20% stage IV) of their disease. The prevalence of advanced-stage disease was significantly higher among women who used traditional medicine before diagnostic confirmation (aPR=1.29, 95% CI [1.10, 1.52]), and in those who waited for > 6 months before diagnosis (aPR=1.35, 95% CI [1.12, 1.63]). On the contrary, it was lower among women who had ever practiced breast self-examination before symptom recognition (aPR=0.77, 95% CI [0.63, 0.96]). The median total interval (symptom recognition to first treatment initiation) was 7 (IQR: 2.7 to 15.7) months. One-fifth of the women started first treatment after one year of first symptom(s) recognition. Adjuvant chemotherapy initiation was delayed (>90 days) in 30% of patients. Only 31.4% (n=137) of the women had received radiotherapy, 64.2% (n=88) of which was adjuvant radiation. Adjuvant radiation initiation was delayed (>90 days) in 56.1% of the women. The overall survival rate at year one was 88.3% (95% CI [84.9%, 91.0%]), and 75.2% (95% CI [70.7%, 79.0%]) at year two. Women diagnosed at stage I had a two-year survival of 100% in contrast to 26.7% at stage IV. The risk of death was significantly higher among women who had a symptom interval of >3 months (adjusted hazard ratio [aHR] = 1.87, 95% CI [1.15, 3.03]) and diagnosed with advanced-stages (aHR=3.32, 95% CI [1.81, 6.10]) but lower among those who had surgical (aHR=0.23, 95% CI [0.15, 0.35]) and hormonal therapy (aHR=0.26, 95% CI [0.17, 0.40]). Conclusions: Substantial proportions of women with breast cancer in Addis Ababa have experienced patient and diagnostic delays that contribute to the high proportion of advancedstage breast cancer, and low breast cancer survival rates. The factors identified that contribute to delayed diagnosis and advanced-stage diagnosis are modifiable. These include poor awareness about breast cancer, using traditional and spiritual remedies, downplaying the clinical importance of the first breast cancer symptoms, health care providers' limited provision of clinical breast examination and delayed referral of women for diagnosis with suggestive of breast cancer symptoms, and longer navigation process to get diagnosis. Once diagnosed, significant number of women experienced delay to adjuvant chemo-and radiotherapy initiation. Recommendations: Breast health awareness campaigns that mitigate misconceptions and improve awareness about breast cancer both in the community and frontline health care providers are essential. Interventions to enhance early detection and prompt referral following consultation, and decrease waiting time between symptom recognition and breast cancer diagnosis are needed to improve early-stage diagnosis and survival rate of women with breast cancer. Also, the expansion of cancer diagnostic and treatment centers is necessary to shorten the diagnosis and treatment delays.en-USBreast neoplasm, delay, time intervals, patient interval, diagnostic interval, symptom recognition, stage, survival, Addis Ababa, EthiopiaThesis