Assessing the Diagnosis Delay Among Breast Cancer Patients Attending in a Tertiary Care Hospital in Dhaka

Background: Diagnosis is a key determinant for any disease outcome. For that, we want to find out in which stage a breast cancer patient got admitted in hospital including various methods of laboratory investigations were done at different visits. Objectives: This study was aimed to generate information on the stages that a breast cancer patient got admitted including various methods of laboratory investigations were done at different visits. Methodology: We conducted a cross sectional study at the National Institute of Cancer Research and Hospital, Dhaka, Bangladesh from July 2017-June 2018. We randomly selected a total of 200 patients who came to that hospital through face-to-face interview by using pretested semi-structured questionnaire. Results: A total 77.0% (154) patients investigated Fine Needle Aspiration Cytology (FNAC) at first visit and mean duration for diagnosis was 11 months. Maximum patients came for diagnosis at stage II, III or IV; nobody came at stage I. As consequences, we found that stage of cancer had 7 times more likely to cause diagnostic delay (OR=7.957; 95% CI 3.206-19.749) p <0.0001. Number of consultations was one of the cause for diagnostic delay ( c 2 = 12.825, p <0.0001). Diagnostic delay had strong association between first consultation with physician versus other health care providers ( c 2 = 17.645, p <0.0001). Excluding physicians, first consultation with health care providers also had 3 times more likely to cause delay in diagnosis (OR-3.862; 95% CI1.877-7.944) p <0.0001. Conclusion: Breast cancer patients attended to health care provider at advanced stage. Knowledge, negative perception, social support were the contributing factor for delay in breast cancer diagnosis.


Introduction
Diagnosis of a disease is a complex process of determining and correspond which disease or condition explains a person's symptom and sign. Breast cancer get bigger public health problem all over the world, especially in developing regions, where the incidence is growing as much as five percent per year. 1,2 Each year, breast cancer is newly diagnosed in more than 1 million women worldwide with more than 400,000 women die from it. 1,3 Though in Bangladesh, there is no national cancer registry but it is predicted that it will be an increasingly important cause of morbidity and mortality in the next few decades. 6 Bureau of Statistics of Bangladesh stated that, cancer is the sixth leading cause of death. The estimated incidence of 12.7 million new cancer cases projected to 21.4 million by 2030. International Agency for Research on Cancer has estimated cancer-related death rates in Bangladesh to be 7.5% in 2005 and 13% in 2030. 6 Diagnosis of a disease has a pivotal role to start cancer treatment. Maximum diagnosis of breast cancer usually done at advanced stage which leads to delay in starting breast cancer treatment. Delay diagnosis of breast cancer represents a significant problem in Bangladesh. It influences the survival rate and out pocket expenditure simultaneously. As cancer is a non communicable disease, more than two third of total expenditure is throughout pocket payments. 6 Diagnosis of breast cancer is often challenging. False negative mammography or FNAC 7 also has a pessimistic impact on cost and choice of treatment. 7 The process of diagnosis may seem long and frustrating because, first patient and family member agree that it is a problem to seek medical help and visit health care provider. After that, physician correlates with physical finding by clinical examination and laboratory finding. If expected laboratory finding not matched with clinical examination or patient complain, repeated lab investigation is done. In Bangladesh, around one fourth respondents did not know to whom first seek help for breast cancer diagnosis and treatment. 8 Delayed detection of breast cancer increases the chance of metastases as well mortality and morbidity. Early detection of cancer is important because delay is preventable and earlier treatment can lead to improved survival. To the best of our knowledge, no study has been previously conducted in Bangladesh to assess the diagnostic delay. Limited studies have been conducted in South East Asian. [9][10][11][12][13] This study was conducted to generate information on the stages that a breast cancer patient got admitted including various methods of laboratory investigations were done at different visits to determine the duration required for breast cancer as well to whom and in which institution they go first, how many visits required and also to find out the factors related to the diagnostic delay.

Materials and Methods
A cross sectional study was conducted during July 2017-June 2018 with a total of 200 samples which were selected randomly from the National Institute of Cancer Research and Hospital, Dhaka, Bangladesh from the listed patients who attended in the outpatient department of chemotherapy day care centre for treatment after diagnosis of breast cancer. To avoid recall bias newly diagnosed primary carcinoma (breast cancer) patients were selected. Inclusion criteria were diagnosed breast cancer patients irrespective of age, marital status, education, religion and customs, admitted in the hospital and patients of breast cancer who was provided informed written consent. Patients with mental disability; seriously ill recurrence of breast cancer, treatment failure with metastasis; hearing impairment; and patients who were not provided informed written consent were excluded from the study. Patients were randomly approached and perspectives of the study were explained to the respondents and all eligible patients signed the consent forms before a face to face interview was conducted. Though sample size was calculated as 384 (p=49.1% 14 , z=1.96, d=0.05) but based on the exclusion criteria, in total 200 patients (52%) completed the interview. The reasons for non completion included the patients being too tired, having poor physical health, lack of interest. Each breast cancer patient was given chemotherapy at 21 days cycle. Daily approximately 7 breast cancer patients came for chemotherapy from different parts of the country. The interview was taken to 40 -45 minutes in length. Ethical Clearance was obtained from Institutional Review Board (IRB) of NIPSOM (NIPSOM/IRB/2016/18) and written permission was obtained from hospital authority before taking interviews (NICRH/Ethics/2016/204-5). Written informed consent was obtained from all patients who participated in this study in a predesigned consent form. The questionnaire included questions focusing on patient's socio demographic, current treatment status, factor related to diagnostic delay, medical help seeking for diagnosis and treatment. Clinical information such as stage of disease, type of surgical management etc were obtained from medical records. Questionnaire was prepared by reviewing literatures of qualitative study which was done in South East Asian Region and from various models. [9][10][11][12][13]15,16 Statistical analysis Statistical analyses of the data were performed using the Statistical Package for the Social Sciences (SPSS) for Windows, version 23.0 (SPSS Inc.; Chicago, IL, USA). Descriptive statistics like frequency distribution, mean, median, mode, range, standard deviation etc. were calculated by SPSS programme. Association was seen between diagnostic time and other variables by Pearson's Chi-square (F2) 2x2 table at p<0.05 level of significance. To control confounder logistic regression was done.

Results
Out of 200 respondents, maximum patients 77(38.5%) were in 36-45 age group and their mean age was 42 years with mean family income was around BDT 9000 (just over 100$). A total 154 (77 %) patients did FNAC for the first visit. FNAC was ahead one time done by 133 (66.5 %) respondents, two times was done by 56 (28%) and three times by only 6 (3%) respondents. Maximum were diagnosed in at stage III 130 (65.5%) and stage IV 32 (16.0%), only 38 (19%) respondents were in stage II ( After clinical examination one to six visits was required for laboratory diagnosis to confirm breast cancer. FNAC was done individually or along with ultra sonogram. A total of 52 (26.0%), 49 (24.5%), 20 (10%) patients were done both ultrasonogram and FNAC at 1 st , 2nd and 3 rd visit respectively beside this 43 (21.5%), 48 (24.0%), 18 (9.0%) patients was done biopsy at 2 nd , 3 rd and 4 th visit respectively. As In order to prediction of the effects of independent variable on time to diagnosis, logistic regression was used. Thought all logistic regression analysis odds ratio greater than 1.00 (OR>1.00) indicated increased likelihood of diagnostic delay. Conversely, odds ratio less than 1.00 (OR<1.00) indicated decreased likelihood of diagnostic delay.
The logistic regression was performed to see the diagnostic delay with presentation of patients during diagnosis (

Discussion
Diagnosing breast cancer usually begins when a lump is found in breast or a screening mammography suggests a problem with the breast, but in developing country ultrasonography is one of a choice. 17 Shieh SH found that women who received an MRI examination on first visit also had the disease diagnosed much earlier compared with those without the test (8.4 vs. 28.9 days; p < 0.001). 18 But in this study, a total of 154 (77.0%) patients did Fine-Needle Aspiration Cytology (FNAC) as a first choice for diagnosis. Ultra sonogram was the second choice one. Goodson WH found that Fine-Needle Aspiration is the least invasive way to obtain tissue, but due to untrained physician, one percent women undergo delay . 19 In this study, it was showed that FNAC was not always accurate for that, one fourth of the patients repeated FNAC for 2-3 times. Delay was associated with a benign mammography report (relative risk, 10.8; 95% confidence interval, 5.1-22.8), a woman finding her own mass (relative risk, 3.3; 95% confidence interval, 1.8-6.2), and current hormone replacement therapy (relative risk, 3.1; 95% confidence interval, 1.2-8.5). 19 In this study, diagnostic delay was associated with the cancer stage and type of 1st diagnostic centre (p=.059), number of consultation for diagnosis (p<0 .0001).
Shieh SH found that number of hospitals visits was also associated with the delay in diagnosis. It took 10 times longer to have the breast cancer diagnosed for women visiting three hospitals compared with women visiting only one hospital (147.4 vs. 14.3 days; p < 0.001). 18 As because, patients had already in advanced stage, to reduce system loss and rapid diagnosis as well easy accessibility of health services, three fourth patients attended at private hospital.
Norsa'adah found that the median time to diagnosis was 5.5 months. The frequency of diagnosis delay of more than 3 months was 72.6% and delay of more than 6 months occurred in 45.5% of the cases. The factors associated with diagnosis delay included the use of alternative therapy (odds ratio (OR)  7 Ermiah E also found that the median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3-6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: symptoms were not considered serious in 27% of patients. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom (s) that did not include a lump (p < 0.0001), with women who did not report In this study, it was to be found that the mean of diagnostic delay was 11 months with influencing factors were, all the respondents 200 (100%) had lack of knowledge on breast cancer, 95%(n=190) had wrong perception, 122 (61.0%) respondents were delayed due to mentally upset, 157 (78.5%) had economic cause to delay in diagnosis, 123 (61.5%) had lack of social support , 148 (74.0%) had poor health care service delivery and utilization and 111 (55.5%) delayed due to received alternative treatment, however transportation factor was not the cause of delay. Abu-Helalah found that patients with diagnosis delay were 49.1%. The main reported reasons for delay in presentation were ignorance of the nature of the problem (65.6%), limited/lack of knowledge that symptoms were suggestive of cancer diagnosis (16.7%), and misdiagnosis (16.7%). 14 Toure also found that lack of financial means (36%), cultural habits with first intent traditional treatment (41.1%), misdiagnosis (7.1%) and lack of therapeutic care cause delay in diagnosis. 21

Conclusion
Diagnosis of breast cancer usually starts with a lump on breast or axilla. Patient herself or family member wasted time to take decision to whom and where they go first for seeking medical help. After appearing the symptom of breast cancer patients should know where she go and what to do. There should be a proper guideline of investigation for accurate diagnosis of breast cancer. Avoid repeated investigation trained and skilled personnel should be required.