Factores asociados al intervalo de tiempo entre la aparición de síntomas y la primera visita médica de mujeres con cáncer de mama

Cad Saude Publica csp Cadernos de Saúde Pública Cad. Saúde Pública 0102-311X 1678-4464 Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz Las mujeres que presentan tumores avanzados de cáncer de mama son comunes en Brasil. Se sabe poco sobre los factores que contribuyen al retraso en la búsqueda de atención. El objetivo de este estudio fue identificar los factores asociados a los intervalos de tiempo más largos entre la aparición de los síntomas de cáncer de pecho y la primera visita médica en el Distrito Federal, Brasil. El análisis incluyó a 444 mujeres con síntomas de cáncer de pecho, que fueron entrevistadas entre septiembre 2012 y septiembre 2014, durante el tratamiento de cáncer de mama en nueve hospitales públicos del Distrito Federal. Pacientes con enfermedad metastásica en el diagnóstico no estuvieron incluidos en este estudio. El resultado fue el intervalo de tiempo entre la aparición de los síntomas y la primera visita médica, si > 90 (34% de pacientes) o ≤ 90 días. La regresión logística se usó para estimar odds ratios (OR) y los intervalos de 95% de confianza (IC95%). En el análisis multivariado, los > 90 días de intervalo estuvieron significativamente asociados con pacientes que no se realizaron mamografías y/o ultrasonidos en el pecho en los dos años previos al diagnóstico de cáncer de mama (OR = 1.97; 95%CI: 1.26-3.08), y en estadios más avanzados (OR = 1.72; 95%CI: 1.10-2.72). Además, hubo una probabilidad más baja de retraso en pacientes con niveles más altos de educación (OR = 0.95; 95%CI: 0.91-0.99). Una proporción relativamente alta de pacientes con cáncer de pecho en el Distrito Federal sufrieron retrasos para realizar las primeras consultas médicas tras la aparición de los síntomas. El aumento de la concienciación sobre el cáncer de mama, especialmente entre mujeres con bajo nivel educacional y quienes no participaron en programas de mamografías pudieron contribuir a la reducción de este retraso. Introduction Breast cancer is the most frequent malignant tumor in women in most countries worldwide. It is the leading cause of death from cancer in women of low and medium Human Development Index countries, where it represents 14.9% of all cancer deaths 1. In Brazil, this neoplasm is the most common malignancy in women after non-melanoma skin cancer. The frequency of new cases of breast cancer is also high in the Federal District. It was estimated that 1,020 new cases of breast cancer would be detected there during 2018, which represents the fifth highest incidence rate (62.1 cases per 100,000 women) in Brazil 2. The mortality rate of breast cancer has been increasing in Brazil 3 and actions to control this cancer, as proposed by the Brazilian National Cancer Institute (INCA), consist in improvements in both early disease detection and prompt treatment 4. For early detection, it is important to promote breast cancer screening among the target population and quick identification of breast cancer signs and symptoms by women and/or health professionals, as well as to improve access to health services for diagnosis and treatment 5. However, previous studies in Brazil have shown that women present limited knowledge about some breast cancer signs and symptoms 6,7 and many of them do not routinely undergo mammography screening 8. These weak points, besides limitations in health services access, may lead women to take longer to attend a first medical visit after identifying any breast alteration suggestive of cancer. The interval prior to the first consultation includes the time interval between the detection or awareness of a body change defined as “appraisal time” and the time interval of perceiving a reason to talk about the symptoms with a health professional at the first consultation, defined as “help-seeking interval” 9. In the Brazilian context, it is believed that the “appraisal time” and “help-seeking interval” are more relevant than difficulty to obtain the first medical consultation given a national study showing that 97.6% of the interviewees obtained a medical appointment on their first attempt 10. Previous studies suggested that longer time intervals between the onset of symptoms and the first health care visit were associated with older age, lower educational level and lower family income 11,12, but few of such studies were performed in Brazil 13,14, which limits the understanding of such factors regarding the breast cancer in our country. Based on the above considerations, the aim of this study was to investigate the time interval between the onset of suggestive symptoms of breast cancer and the first medical visit. We further investigated which factors were associated to longer intervals. Material and methods This cross-sectional study started with 600 incident breast cancer patients hospitalized for breast cancer treatment in nine public hospitals of the Federal District, Brazil. Patients with metastatic disease identified before treatment were not included in the study. Data collection was carried out between September 2012 and September 2014. All women were interviewed using a structured questionnaire. Clinical data was retrieved from hospital records and a total of 444 (74%) consecutive symptomatic women at the first medical visit were included in the analysis, disregarding refusals. Sample size calculation was based on the estimation that 1,800 new breast cancer cases would be diagnosed in the Federal District during the period of data collection 15. We considered that 40% of these cases would be treated in private services (Brazilian National Agency for Supplementary Health. http://www.ans.gov.br/anstabnet/cgi-bin/dh?dados/tabnet_tx.def, accessed on 04/Dec/2014) and the time interval between the onset of symptoms and the first medical consultation would exceed 90 days in 30% of cases 14. The variable of interest was the self-referred time interval between the onset of the suggestive symptom of breast cancer and the date of the first medical visit. This variable was dichotomized - ≤ 90 days and > 90 days - as this was the cut-off point used in other studies 11,16,17,18. The presence of a palpable lump, skin and/or nipple retraction, hyperemia, bulging, abscess or pain in the breast, ulceration, nipple discharge, change in breast size, and the presence of axillary nodules were considered signs/symptoms. The first medical visit was defined as the moment when the patient was first examined due to her complaint regarding the breast. Other variables were considered, such as patient sociodemographic characteristics (age, marital status, place of residence, educational level, and average family income), family history of breast cancer, periodicity of breast self-examination, date of last mammography and/or breast ultrasound before diagnosis, date of last clinical breast examination before diagnosis, and stages grouped according to the sixth edition of the TNM Classification of Malignant Tumors19. Family income per month was expressed in US dollars (1 USD = 2.7 BRL on December 31, 2014). The descriptive analysis estimates frequencies for categorical variables and measuring central tendency and dispersion for continuous variables - mean and standard deviation (SD) or median and range. Some variable categories were abandoned for the few cases. Bivariate and multiple logistic regression models were performed. Variables that showed p-value ≤ 0.25 in the bivariate analysis were tested in the multiple model 20 by a stepwise forward method, and remained in the model when p-value < 0.05. The IBM SPSS Statistics v.20.0 software (https://www.ibm.com/) was used for the analysis. This study was approved by the Ethics Research Committee of the Health Sciences Teaching and Research Foundation, Federal District Health State Department (Ethics Approval n. 99,313) as recommended by Resolution n. 196/1996 of the Brazilian National Health Council. All participants signed an informed consent form before the interview. Results Out of the 444 women included in this analysis, the mean age at diagnosis was 52.3 years (± 12.8) and the most frequent age group was 50 to 69 years (Table 1). The following characteristics were more prevalent: being married or living in a stable union and dwelling in the Federal District. The mean number of schooling time was 7.8 years (± 4.7) and the average family income was USD 502.22 (ranging between USD 25.90 and 12,963.00). Table 1 Characteristics of 444 symptomatic women with breast cancer treated at public hospitals in the Brazilian Federal District between September 2012 and September 2014. Characteristics n % Age group (years) < 40 81 18.2 40-49 120 27.0 50-69 195 43.9 > 70 48 10.8 Place of residence Federal District 281 63.3 Other 163 36.7 Marital status Single 98 22.1 Married or living with a partner 233 52.5 Divorced 57 12.8 Widow 56 12.6 Family income (USD per month) * > 502.20 230 53.1 ≤ 502.20 203 46.9 Years of schooling Mean 7.8 years (SD = 4.7) Family history of breast cancer No 323 72.7 Yes 121 27.3 First-degree relative 45 37.2 Second-degree relative 76 62.8 Breast self-examination periodicity Once a month 212 47.7 Less frequent 232 52.3 Mammography and/or breast ultrasound periodicity ** ≤ 2 years 168 39.3 > 2 years 93 21.8 Not performed before 166 38.9 Clinical breast examination periodicity *** ≤ 1 year 158 37.5 > 1 year 193 45.8 Not performed before 70 16.6 Stage group 0-IIA 156 35.1 IIB-IIIC 288 64.9 SD: standard deviation. * Information available for 433 patients; ** Information available for 427 patients; *** Information available for 421 patients. The time interval between the onset of suggestive signs/symptoms of breast cancer and the first medical visit showed a median of 39 days (ranging between 0 and 1,857 days), with 34% occurring up to 90 days. In both bivariate (Table 2) and multiple regression (Table 3) analyses, the variables that showed a statistically significant association with a longer interval (> 90 days) were patients not performing mammography and/or breast ultrasound in the two years prior to breast cancer diagnosis (OR = 1.97; 95%CI: 1.26-3.08), and with more advanced stages (OR = 1.72; 95%CI: 1.10-2.72). Furthermore, there was a lower chance of delay in patients with higher levels of education (OR = 0.95; 95%CI: 0.91-0.99). Table 2 Bivariate analysis. Factors associated with longer time interval (> 90 days) between onset of breast cancer symptoms and first medical visit and associated factors. Characteristics Total Interval between symptom and first visit > 90 days Crude OR 95%CI n % Age group (years) < 50 201 67 33.3 1.00 - ≥ 50 243 86 35.4 1.10 0.74-1.62 Place of residence Federal District 281 98 35.9 1.00 - Other 163 52 31.9 0.84 0.55-1.26 Marital status With a partner 233 72 32.6 1.00 - Without a partner 211 77 36.5 1.19 0.80-1.76 Family income (USD per month) > 502.20 203 65 32.0 1.00 - ≤ 502.20 230 84 36.1 1.20 0.80-1.79 Years of schooling 0.95 0.91-0.99 Family history of breast cancer Yes 121 37 30.6 1.00 - No 323 113 35.9 1.27 0.81-1.99 Breast self-examination performed at least once a month Yes 212 71 33.5 1.00 - No 232 79 34.1 1.01 0.68-1.49 Mammography and/or breast ultrasound periodicity ≤ 2 years 168 39 23.2 1.00 - > 2 years or never performed 259 103 40.5 2.26 1.46-3.49 Clinical breast examination periodicity ≤ 1 year 158 44 28.5 1.00 - > 1 year 263 95 36.1 1.42 0.93-2.18 Stage group 0-IIA 156 38 25.6 1.00 - IIB-IIIC 288 112 39.2 1.87 1.25-2.88 95%CI: 95% confidence interval; OR: odds ratio. Table 3 Multivariate analysis. Factors associated with longer time interval (> 90 days) between onset of breast cancer symptoms and first medical visit and associated factors. Characteristics Adjusted OR 95%CI p-value Years of schooling 0.95 0.91-0.99 0.042 Mammography and/or breast ultrasound periodicity ≤ 2 years 1.00 - > 2 years or never performed 1.97 1.26-3.08 0.003 Stage group 0-IIA 1.00 - IIB-IIIC 1.72 1.10-2.72 0.02 95%CI: 95% confidence interval; OR: odds ratio. Discussion Our results reveal that one third of the sample (34%) had a considerable time interval between the onset of symptoms and the first medical consultation. Three variables were associated with this delay: lower educational level, not undergoing mammography and/or breast ultrasound in the two years prior to the diagnosis, and cases diagnosed at more advanced stages. The median interval between the onset of signs/symptoms and the first medical visit observed - i.e., 39 days - was higher than reported in previous studies in Brazil 13,14. Over one-third showed an interval exceeding 90 days, which is longer than in other countries 16,21,22,23. Although methodological differences between studies and different characteristics of health services among countries hinder the results comparison, we consider that devising actions to reduce this interval in the Brazilian scenario should be a priority, given that longer intervals are associated with lower survival rates of breast cancer 24. To reduce this interval, it would be important to remember that women with lower educational levels were more susceptible to have longer intervals, which is consistent with results from other studies 21,25,26. Lower educational levels are also associated with lower levels of awareness and recognition of breast cancer warning signs 27,28. Furthermore, knowledge about breast cancer signs/symptoms among the Brazilian population is limited. A recent study including 478 women aged 40 or older in the city of Rio Branco, in Northern Brazil, reported that women were aware of some signs/symptoms such as lumps, nipple discharge, and breast discomfort. However, most of the sample did not identify nipple retraction, redness of breast skin and/or nipple discharge as breast cancer signs/symptoms 7. The difficulty in recognizing breast cancer warning signs may have resulted in longer intervals prior to the first consultation. Moreover, note that the perceived barriers regarding access to health services are more frequently observed among people with worse socioeconomic conditions, in addition to previous experience and judgment regarding health services that may lead to avoidable delays and late diagnosis 29,30. Access to outpatient secondary services such as mammography is limited in Brazil 31. An increase in the rate of mammography screening coverage among the target population should contribute to an earlier diagnosis. Although the INCA advises biennial mammography screening for women between 50 and 69 years 4, there is no population-based breast cancer screening program in the country and women only have access to screening strategies opportunistically 8. Besides, there is a reason to believe that mammography performance contributes to breast cancer awareness among patients and health professionals. An association was observed in other studies between delay at attending and patients not undergoing mammography or breast ultrasound 17,21,23,32. Breast self-examination and clinical breast examination periodicity were not associated with a longer time interval to attend the first medical visit constrasting with previous studies 21,32,33. Moreover, these practices are not recommended for breast cancer screening on recent national directive 4. Finally, there was an association of more advanced stages with delay to attend the first medical consultation as in other studies 13,16,34. This association was found in both bivariate and multivariable analyses, which points to the importance of this delay regarding the disease outcome. Women with advanced breast cancer tumors at medical appointment are common in Brazil, with more than 70% of the tumors diagnosed at stage II or higher 35. This highlights the importance of speeding up the first medical visit after the onset of symptoms by improving breast cancer awareness to detect the disease at earlier stages 36. No association was observed between the delay to attend the first medical visit after the onset of symptoms and age, marital status, family history of cancer, income, or distance between place of residence and health care facilities, unlike what was previously reported 16,18,21,37. This inconsistency may result of various circumstances: methodological differences; the fact that these events depend on the sociocultural context 38; insufficient research about these aspects related with delay 39. This is one of the largest studies performed in Brazil focusing on this issue, but it has some limitations. Patients with metastatic disease at diagnosis were not included in our study and this may have decreased the delay interval. Moreover, patients might not accurately remember when certain events occurred in their lives, which might translate into some memory bias; to minimize this risk, this study included only incident breast cancer cases. Furthermore, there is a possibility that some patients did not report the real time interval to avoid shame or embarrassment, as previously reported 24. In conclusion, in a relatively high proportion of breast cancer patients in the Federal District, the first medical visit occurs long after the onset of symptoms. 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