Adherence to Adjuvant Hormonal Therapy and Associated Factors Among Women with Breast Cancer Attending the Tikur Anbessa Specialized Hospital, Addis Ababa Ethiopia, 2019: A Cross-sectional Study

Introduction

Breast cancer has remained a significant public health concern worldwide, including in Ethiopia. It accounts for around one-fourth of all cancer cases and one-sixth of all deaths associated with cancer. Breast cancer is the principal cause of cancer mortality, according to the Addis Ababa cancer registry, which precedes cervical cancer. In Ethiopia, nevertheless, hormone receptor staining is sometimes not available. However, some studies showed that in every 10 women with breast cancer seven of them were hormone receptor-positive (HR+).^1–4In countries such as Kenya, Tanzania, and Uganda, the prevalence of hormone receptor-positive (ER+/PR+) among women with breast cancer was 27%, 40%, and 51%. Tamoxifen is used to treat ER+ BC cancers, in sub-Saharan Africa it is administered without knowledge of receptor status. Besides countries without these facilities blindly administer hormonal therapies.^2,5–9

These therapies include a selective modulator of the estrogen receptor (tamoxifen 20 mg po daily) works by blocking the effects of estrogen and aromatase inhibitors (anastrozole 1 mg po daily) that inhibit the biosynthesis of estrogen. Adjuvant tamoxifen and anastrozole reduce the risk of recurrence in women with ER+ BC by 40% and 12%, and mortality by 33% and 9%, respectively.^10,11 As patients are expected to take the drug for almost 5–10 years, the duration of adjuvant hormonal therapy is relatively extended. Thus, this lengthy oral therapy duration stressed whether or not the patient complied with the prescribed regimen. Despite its efficacy in treating breast cancer only one in two patients adhered to the medicated AHT regimen. Consequently, it then accelerates their mortality risk.^10,12–18

Adherence is a multidimensional problem that is strongly linked with adherence to tamoxifen and AIs linked to the patient, therapy, health-care system, sociodemographic, disease, and behavioral factors.^18–20 In the Nigeria study, financial burdens and side effects were the most factors responsible for not complying with the regimen.²¹ The excellence or incapability to conform to adjuvant hormone therapy was the duration, while the increase in medication duration resulted in a reduction in adherence owing to intolerable adverse effects. For example, tamoxifen and anastrozole adherence rates in the first to fifth years were around 79% to 65% and 80% to 72%, respectively.^13,22–24

Different efforts have been made to mitigate the concern of adherence by educating patients on medication and also its adverse effects, skills on self-management of side effects, strengthening connections between patient and provider and securing health-care coverage, providing connections to social support and designing policies and practices to overcome factors that influenced adherence to AHT. Consequently, this improved breast cancer outcomes amongst survivors of breast cancer care.^11,25–30 There is, however, a paucity of reporting on the adherence status of Ethiopian women receiving adjuvant hormonal therapy and its relevant factors in the study area. This research was therefore aimed at determining adherence status and associated factors for adjuvant hormone therapy among patients with female breast cancer attending TASH oncology center.

Methods and Materials

Study Design, Period, and Setting

An institutional based cross sectional study was conducted from March to April, 2019 at the oncology center of TASH. The hospital is found in Addis Ababa Lideta Sub City. This hospital worked as the nation’s sole cancer referral center and has given radiotherapy, chemotherapy, concurrent cancer treatment services and palliative care for patients with cancer. According to the registry in the unit, more than 10,000 cancer cases were seen in this hospital per year. The most common cancer cases seen in this hospital were breast, cervical, and sarcomas.¹

Population

All women diagnosed with breast cancer in the TASH oncology center were the source population and those are available during the data collection period were the study population. Patients who were severely ill and incompetent to interview were excluded.

Sample Size Determination and Sampling Procedure

To determine the sample size assuming number of the study subjects as n, the standardized normal distribution curve value for 95% confidence level (1.96), taking 50% of proportion because no previous similar study on adherence to adjuvant hormonal therapy and associated factors among women with breast cancer. By applying single population proportion formula for a cross-sectional survey, the sample size was 384.

n===384

where Z=1.96; P=0.5; d=0.05.

Since the flow of patients during data collection period was less than 10,000, then a correction formula was applied.

nf=== 196

where n_f=desired sample size; n=the calculated sample size; N=total population (during data collection period).

After adding a 10% nonresponse rate the final sample size was 216. Then, data was collected by using a systematic sampling method. Every two patients were interviewed.

Operational Definition

Adherence: those who score medication possession ratio ≥80%.

Nonadherence: Those whose score medication possession ratio <80%.²

Adjuvant hormonal therapy: includetamoxifen 20 mg po/day and anastrozole 1 mg po/day in this study.

Data Collection Tools

Data was collected using a pretested and semi-structured face-to-face interview and patient health records were used. The question was translated in to Amharic by experts in both languages before, and translated back to English after data collection to ensure its consistency.

The interview-guided questionnaire was used to collect information on patients’ sociodemographics, clinical and health-care system related characteristics. Patient charts review guide and prescription paper were used to identify date and days of supply and types of the AHT. Adherence was defined by the medication possession ratio (≥80%).^2,3 Medication possession ratio (MPR), defined as the days’ supply of medication during the period from the first dispensing to the last dispensing in the time period of three months, divided by number of days.

Data Quality Control

Data quality assurance was applied using different techniques. Firstly, a content validity test was conducted. Then the pretest was done at Hawassa University Specialized Hospital by taking 5% of the study sample. Findings and experiences from the pretest were utilized in modifying the data collection tool. Training was given by the principal investigator for one day for data collectors and supervisors. The supervisor and principal investigator reviewed each questionnaire daily and checked for completeness and were then edited; the necessary feedback was given to the data collectors the next morning.

Data Processing and Analysis

Data were first checked, coded and entered using EpiData version 4.4.2.1 and transferred to SPSS version 25. Description of frequency, mean, median, proportion, and SD was used. Significance was determined using odds ratios with 95% confidence intervals. To assess the association between the different predictor variables with the dependent variable, first bivariate analysis were conducted between each independent variable and outcome variable, those eligible with P-value <0.2 were then entered in multivariate analysis. Those variables with a P-value <0.05 and a 95% confidence interval were regarded as significant factors using an binary logistic regression.

Results

Sociodemographic Characteristics of the Study Participants

From 216 selected participants, 209 were involved in the study with a response rate of 97%. Of 209, 88 (42.1%) were in the age group 45–65 years, 121 (57.9%) were from urban, 103 (49.3%) were high school and above, 154 (73.7%) of the participant were married, 139 (66.5%) were Orthodox by faith, 82 (39.7%) were Amhara by ethnicity, 117 (56%) were housewives (Table 1).

Table 1 Sociodemographic Characteristics of Women with Breast Cancer Attending Oncology Center at TASH, Addis Ababa, Ethiopia, 2019 (N=209)

Patient-related Factors

Of 209, 207 (99.1%) of the study participants had no smoking habit, 205 (98.1%) never drank alcohol before and 140 (67%) were socially supported (Table 2).

Table 2 Patient-related Variables of Women with Breast Cancer Attending Oncology Center at TASH, Addis Ababa, Ethiopia, 2019 (N=209)

Disease-related Factors

Of 209, 190 (90.9%) had no family history, 187 (89.5%) were ductal carcinoma, 151 (72.2%) with advanced stage, 143 (68.4%) were postmenopause women, 186 (89.0%) with unknown receptor status, 205 (98.1%) were with one breast unilateral, respondents who received chemotherapy, surgery and radiotherapy were 194 (92.8%), 188 (90.0%) and 51 (28.2%), respectively, 189 (90.4%) undergoing mastectomy, 159 (76.1%) have no comorbidity, Among 50 (23.9%) those who had comorbidity; 24 (48%) were diabetic, 12 (24%) were HIV/AIDS, 8 (16%) had a heart problem and 6 (12%) had a respiratory problem (Table 3).

Table 3 Disease-related Variables of Women with Breast Cancer Attending Oncology Center at TASH, Addis Ababa, Ethiopia, 2019 (N=209)

Medication-related Factors

Of 209, 118 (56.5%) were on tamoxifen, 62 (29.7%) initiated in the year 2019, 122 (58.4%) had not experienced side effects. Among 87 those who reported side effects; nausea and vomiting 25 (28.7%), tiredness and fatigue 23 (26.4%), joint and muscle pain 20 (23.0%), weight gain 9 (10.3%), sleep disorder 7 (8.0%), hot flash 3 (3.4%) (Figure 1, Figure 2). One hundred and twelve (53.1%) were getting their medication free of charge, 110 (52.6%) had follow-up of one year (Table 4).

Figure 1 Side effects of adjuvant hormonal therapy’s reported by the respondents among women with breast cancer attending oncology center at TASH, Addis Ababa, Ethiopia, 2019 (N=209).

Table 4 Medication-Related Variables of Women with Breast Cancer Attending Oncology Center at TASH, Addis Ababa, Ethiopia, 2019 (N=209)

Health Care System-related Factors

Among the respondents, 136 (65.1%) reported adjuvant hormonal therapy is not available, 151 (72.2%) have had thorough therapeutic communication from a health-care provider, 102 (48.8%) took more than seven hours to reach hospital (Table 5).

Table 5 Health-care System-Related Factors of Women with Breast Cancer Attending Oncology Center at TASH, Addis Ababa, Ethiopia, 2019 (N=209)

Prevalence of Adherence to Adjuvant Hormonal Therapy

The overall adherence to adjuvant hormonal therapy in the current study was 77.5% (95%CI; 71.3–83.3) (Figure 1).

Figure 2 AHT adherence among women with breast cancer attending oncology center at TASH, Addis Ababa, Ethiopia, 2019 (N=209).

Factors Associated with Adherence to Adjuvant Hormonal Therapy

A binary logistic regression model was used to identify factors that affect the outcome variable. In bivariable analysis; place of residence, educational status, getting social support, family history of breast cancer, types of breast cancer, stage of breast cancer, types of hormonal therapy, side effects, types of surgery and types of payment were fitted at P-value <0.2. But in multivariable analysis, getting support, types of hormonal therapy, side effects, thorough therapeutic communication, types of surgery were significantly associated with the outcome at P-value <0.05 with 95%CI. Being socially supported (OR=3.959, 95%CI: 1.570–9.980), Being on anastrozole (OR=0.139, 95%CI: 0.040–0.485), Getting a thorough therapeutic communication (OR=4.590, 95%CI: 1.061–19.863), undergoing mastectomy (OR=0.215, 95%CI: 0.059–0.788); having side effects (OR=0.210, 95%CI: 0.085–0.517), were found to be significantly associated in multivariate analysis (Table 6).

Table 6 Bivariate and Multivariate Analysis of Factors Associated with Adherence to AHT Among Women with Breast Cancer Attending Oncology Center at TASH, Addis Ababa, Ethiopia, 2019

Discussion

A central component of breast cancer patients who are undergoing hormone therapy is adherence to adjuvant hormonal therapy. However, little is known about the status of women adhering to this therapy in Africa, including Ethiopia. Therefore, the purpose of this study was to assess adherence to adjuvant hormone therapy and the associated factor of TASH breast cancer among women. This study showed that the prevalence of adherence was 77.5%. The current study is in agreement with studies conducted in Brazil 76.3%,³² Sweden 79%,³³ New York 76%,³⁴ North Carolina 78%,³⁵ another study in North Carolina 81.7%,³⁴ and Nigeria 75%.²¹ The similarities may be attributed to the adherence measurement method, sample size, study nature, study population. Except in Nigeria, where their socioeconomic status and sample size may be almost similar. The current study finding is higher than studies conducted in Rome 60%,³⁶ Ireland 67.8%,³⁷ China 63.1%,³⁸ Singapore 40.8%,²⁵ and Texas 44%.³⁹ The difference could be the population of the study, different tools for measuring adherence, sample size, and design of the study. However, our results were lower than studies in Sweden 92%⁴⁰ and South Carolina 91.4%.⁴¹ Sample size, study design, different socioeconomic status, and study duration could differ. In multivariate analysis the following factors were associated with adherence to adjuvant hormonal therapy. In the current study, those who were getting social support, being on tamoxifen, getting thorough therapeutic communication about treatment, undergoing lumpectomy, lack of side effects were found to be significantly associated in multivariate analysis.

A significant variable that affected adherence was obtaining social support in the current study. Those getting social support from others were nearly four times more committed than those who did not. This finding is consistent with the study conducted in northern California,⁴² UK,⁴³ and a study from Los Angeles, California, Houston, and Texas.⁴⁴ These similarities might be attributed to supportive social reinforcement, emotional support, as well as comforting them to comply with the medication and providing a better influence on adherence to the medication.

In the current study, those who had thorough therapeutic communications with the health-care provider about their treatment are 4.6 times more likely to be adherent than those who did not. This finding is supported by the studies conducted in California,⁴⁵ and the UK.⁴³ These similarities could be patient–provider interaction and effective communication about the use of medicines had a positive impact on AHT adherence. In this study, compared to those who had no side effects, of those who had encountered side effects around 79% were apt to become nonadherent. This result is consistent with the result of different studies in North America, Europe, and Australia,¹⁷ China,³⁸ California,⁴⁵ Ireland,³⁷ New Zealand,⁴⁶ and Nigeria.²¹ The similarities might be due to the unbearable side effects such as hot flash, nausea, mood swings and muscle or joint pain. In this study, those who were on anastrozole were 86% less likely to have adhered than those who were on tamoxifen. This finding is in agreement with studies conducted in Singapore,²⁵ North America,⁴⁷ and Canada.⁴⁸ These similarities might be because those on anastrozole appear to complain of more muscle pain and joint stiffness and/or pain and a higher risk of fracture, as they have different side effect levels. In the current study, those who have to undergo lumpectomy were about 78.5% likely to be adherent compared to those who had a mastectomy. This finding is supported by the study conducted in Texas.⁴⁹ The similarities may be attributed to the fact that they are less at risk of being disregarded because their entire breast has been removed. Those undergoing lumpectomy, however, are also afraid of residue during surgery, that is why they tend to be more adherent than those undergoing mastectomy.

Limitations

Even though this study involved a relatively small sample size, the establishment of a causal relationship could not be possible since it is a cross-sectional study. In addition, the study was conducted in one setting which could not represent the whole of the country.

Conclusion

In general, the overall adherence to AHT was good for women with breast cancer. Factors such as types of adjuvant hormone therapy, lack of side effects, types of surgery, getting social support, and thorough therapeutic communication were strongly linked with adherence to them. Much has to be achieved by resolving the abovementioned factors and ensuring the relevance of recommended therapies to scaling up medication adherence. Side effects of the drugs, good social support and effective communication with a patient should be given great emphasis. Adherence counseling instructions on adjuvant hormone therapy for breast cancer should also be created. In addition, they can work on promoting AHT adherence, including the distribution of leaflets, as an alert, using mobile message technology. Finally, various adherence assessment tools should be used by future researchers and different study designs should be warranted, ie longitudinal study. In addition, they need to evaluate the impact of adherence to AHT on the outcome of breast cancer.