Journals | Policy | Permission

World Journal of Oncology

Original Article

Volume 14, Number 4, August 2023, pages 300-308

Assessing Adherence to Adjuvant Hormone Therapy in Breast Cancer Patients in Routine Clinical Practice

Adjuvant treatment with aromatase inhibitors (AIs) or tamoxifen (TMX) for 5 years in estrogen receptor (ER)- or progesterone receptor (PR)-positive breast cancer (BC) patients is known to increase disease-free survival (DFS) and overall survival (OS) [1]. However, adherence to hormone therapy (HT) in BC patients is poorly understood in routine clinical practice worldwide [2-9], posing a challenge with increasing interest. A limited number of different population-based studies have assessed adherence to adjuvant hormonal therapy among women with BC in routine clinical practice worldwide [2-8], posing a challenge with increasing interest [2-8].

A systematic review published in 2012 showed that 31.0-73.0% of patients discontinue HT [9], and other systematic review published in 2022 reported that adherence at 5 years of HT treatment ranged from 33.3% to 88.6%, resulting in an increased risk of relapse [10].

Treatment adherence depends on several factors. Some of these factors are related to the treatment itself (for example, its duration or certain adverse effects), and other factors are related to the patient (age, comorbidities, lack of understanding of the importance of continuous treatment, and the psychological profile and polypharmacy).

Treatment adherence is the most important modifiable factor impacting treatment outcomes. The present study is important since it is crucial to assess outcomes in routine clinical practice to improve the quality of care and provide the best possible care.

The aim of this study was to assess adherence to HT in routine clinical practice.

This cross-sectional, descriptive study was performed at the Breast Health Unit of the Hospital de Clinicas, Uruguay, from May 2019 to May 2021. Patients aged 18 years or older, diagnosed and treated for stage 0-III ER/PR-positive BC and started HT between April 2017 and May 2019 were included. The follow-up period for each patient was 24 months from the first prescription. All patients signed an informed consent form by which they agreed to participate in the study and complete the questionnaire indicated below, in the medical consultation two year from start of HT, authorizing the use of the information arising from the questionnaire in this research.

Different methods are used to assess treatment adherence, and none of them are considered the “gold standard”. Thus, combining several techniques is recommended.

Two methods were used in the present study: the pharmacy dispensing record and the Morisky-Green adherence questionnaire. The pharmacy dispensing record is a validated, simple, and reliable method since dispensing at the hospital is centralized and performed monthly. The medication possession rate (MPR) was calculated using the formula: sum of all the days the patient had the drug/number of days the physician prescribed the drug in the study period. For example, for 12 28-day dispensations of anastrozole in a 12-month interval, the MPR is 0.92 (336/365). An MPR ≥ 0.80 was defined as the threshold for good adherence to HT for its ability to predict hospitalizations in prevalent chronic diseases [11].

The Morisky-Green treatment adherence questionnaire assesses compliance directly with the patient, and its use has been validated for chronic diseases. It consists of four questions with a dichotomous answer (yes or no) that assesses the patient’s behavior regarding treatment adherence: 1) Do you ever forget to take the drugs to treat your illness? Yes/no; 2) Do you take your drugs at the indicated times? Yes/no; 3) When you feel well, do you stop taking the drugs? Yes/no; 4) If you eventually feel sick, do you stop taking the drugs? Yes/no.

Patients are considered to adhere to treatment if they answer correctly to the four questions, that is, no/yes/no/no [12].

Adherent patients were those with an MPR ≥ 0.80 who correctly answered the Morisky-Green treatment adherence questionnaire, and non-adherent patients were those with an MPR < 0.80 or who did not correctly answer the said questionnaire.

The pharmacy dispensing record of our hospital was used to assess the number of drugs that patients receive concomitantly with their oncological drugs and for patients who collected medications from other hospital, and the data were collected through detailed study of medical histories.

Polypharmacy is defined as the use of multiple drugs by a patient, although there is no consensus on the minimum number of drugs to define it. At present, the most accepted definition considers the use of five or more drugs at any time, including over-the-counter drugs and dietary supplements [13, 14].

Demographic, work-related and tumor-specific variables that could have affected both adherence to treatment and treatment discontinuation were investigated.

Data were collected through a detailed analysis of medical records, ensuring patient anonymity using an Excel spreadsheet database in which each patient was assigned an identification number.

Variables related to the patient, including age at diagnosis, marital status, occupation, the territory of origin (capital of the country or rest of the country) were recorded.

Variables related to the tumor, including histologic type and grade, pathological tumor size, axillary lymph node status, stage according to TNM classification, human epidermal growth factor receptor 2 (HER2)-positive, ER, and PR status studied by immunohistochemistry, were noted.

Similarly, variables related to the treatment, including the type of adjuvant HT (TMX vs. AI), were also recorded.

Data were extracted from both paper medical records and oncology electronic medical records. The number of drugs of any type collected by patients and whether they collected the prescribed oncological drug was assessed monthly using the information provided by the outpatient clinic.

In the data analysis, the quantitative variable “age” is described by measures of central tendency and dispersion. The qualitative variables (territory of origin, living with whom, level of education, occupation, marital status, stage, and the number of drugs) are described by their absolute and relative percentage frequencies.

The association between qualitative variables and adherence was assessed using the Chi-square test. The mean ages of both groups: adherent/non adherent was compared with Student’s t-test.

The odds ratio (OR) for non-adherence to treatment (to any treatment and then discriminating according to type of treatment) and its 95% confidence interval were estimated. A significance level of α = 0.05 was considered in all cases. All analyses were performed using R version 4.0.4.

The study population was divided into two groups: adherent patients (patients with an MPR ≥ 0.80 who answered correctly to the four questions in the questionnaire) and non-adherent patients (patients with an MPR < 0.8 or who did not answer correctly to the four questions of the questionnaire).

The study was approved by the Ethics Committee of the Hospital de Clinicas, Udelar. All participants signed an informed consent form before being included in the study. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

The study included 118 patients diagnosed with early HR-positive BC candidate for adjuvant HT; 10 patients were excluded because they did not initiate HT. The mean age at diagnosis was 52.45 years, with a standard deviation of 11.12 years.

Most patients, with data available, were living alone (42.3%) and resided in the capital city (61.0%) (Table 1).

Click to view

Table 1. Epidemiological and Demographic Characteristics of All Patients Included in the Study (N = 118) and for Patients on AI (N = 74) and Tamoxifen (N = 44)

Regarding the level of education, 60 patients (50.8%) completed primary education, 28 patients (23.7%) started secondary education, and three patients (2.5%) attended tertiary education. The remaining data are shown in Table 1.

All tumors were limited to the breast and axilla at the time of diagnosis; 57 patients had T1 tumors, 44 T2 tumors, representing 85.5% of the tumors. In the axilla, 60 patients were N0, and 39 were N1, representing 83.8% of the tumors. As for distribution by stage, 45 patients were classified as stage I (38.1%), 45 patients (38.1%) as stage II, 22 patients (18.6%) as stage III, two patients (1.7%) as stage 0. Regarding the biological profile, 98 patients (83.0%) were ER/PR-positive, and HER2-negative, and 20 patients (17.0%) were ER/PR-positive and HER2-positive (Table 2).

Click to view

Table 2. Clinicopathologic Characteristics, Stage, and HER2 Status of All Patients Included in the Study (N = 118) and for Patients on AIs (N = 74) and Tamoxifen (N = 44)

The patients started HT between 2017 and 2019. All study patients were treated with HT; 65.2% (77) received treatment with AI and the rest with TMX. A total of 36.0% (42 patients) experienced polypharmacy, and 81.0% (96) adhered to the treatment.

All study participants completed the Morisky-Green questionnaire between 2019 and 2021. The analysis of the questionnaire response showed that 12.2% of the non-adherent patients (MPR < 0.8) considered that they adhered to the treatment based on their questionnaire responses. Of the adherent patients, according to the MPR, 25.0% were non-adherent based on the Morisky-Green questionnaire, and the most frequent reason was forgetting to take the drug (85.0%).

The adherence rate (combined adherence measure: Morisky-Green questionnaire and MPR) for patients who completed in 2 years was 81%.

Adherence was associated with age (P = 0.03), with a mean age of 65 vs. 60.3 years for adherent and non-adherent patients, respectively. However, it was not associated with polypharmacy, considering all thresholds used to define polypharmacy, specifically 2 -5 drugs, 5 - 9 drugs, 10 or more drugs, and ≤ 5 drugs or > 5 drugs, neither was associated with the territory of origin, marital status, living alone, level of education, occupation, or stage (Table 3).

Click to view

Table 3. Univariate Associations Between Characteristics of the Sample of 118 Patients Diagnosed With Early ER/PR-Positive BC Treated at the Breast Health Unit and Adherence

The analysis of the factors associated with non-adherence to treatment (to any of them: TMX or AI) showed that the likelihood of non-adherence decreased with age (OR = 0.96), with a lower adherence in younger patients. The adherence profile was similar for both drugs, but the likelihood of non-adherence to treatment decreased in homemakers or retired women compared to employed or self-employed women in the case of patients treated with AI. No statistically significant associations were found between the rest of the variables and adherence to treatment in the group treated with TMX (Table 4).

Click to view

Table 4. Univariate Logistic Models for Non-Adherence to Treatments in the Sample of 118 Patients Diagnosed With Early ER/RP-Positive BC Treated at the Breast Health Unit

Despite Latin America being a diverse region with significant differences among countries in terms of economic development, healthcare systems, and health policies, BC remains one of the leading causes of cancer in women in Latin America. Its incidence has been increasing in the region due to various factors, including population aging, lifestyle changes, and urbanization.

The fight against BC in Latin America requires a comprehensive approach that includes improvements in early detection, access to healthcare, public awareness, and the implementation of effective health policies to enhance outcomes and quality of life for those affected by this disease. In this context, understanding the adherence to HT in BC is essential to ensure the best possible outcome for patients [15, 16].

Adherence to HT in BC patients is reported at a systematic review [9], which indicates that only 40.0% to 70.0% of patients with BC finish their recommended courses of hormonal therapy. Our group has previously assessed adherence to HT in patients treated at the Breast Health Unit in real life, showing a reduction of 30.5% in 5 years [17].

A meta-analysis published in 2011 showed that adjuvant HT for 5 years reduces the risk of relapse and death from BC [1]. Poor adherence and early discontinuation of HT are associated with higher relapse and mortality rates [18, 19]. In addition, treatment adherence is the most important modifiable factor that impacts treatment outcomes. It is crucial to assess such outcomes routinely to improve the quality of care and provide the best possible care. Hence, the importance of the present study.

A study conducted by Hershman et al showed that 60.0% of the patients complied with TMX or AI 2 years after starting it [20]. However, the numbers in our study were higher, 81.0% of the patients continued to receive treatment 2 years after starting it. The high rates of adherence to HT in BC can be attributed to the combination of its availability at no economic cost, ease of administration, good tolerance, demonstrated efficacy, and the perception of its importance in fighting the disease.

BC patients undergoing adjuvant HT are often assumed to be satisfactorily complying with the treatment since they face a serious, life-threatening disease, and the treatment is effective, easy-to-use, and well-tolerated. However, our results indicate that 19.0% of the patients did not adhere to the treatment.

The results also indicate no important difference between the patients’ self-reported adherence based on the Morisky-Green questionnaire and the MPR. According to the results of this questionnaire, only 12.2% of non-adherent patients (MPR < 0.80) considered they adhered to the treatment according to their answers to the questionnaire, indicating good correspondence between both measures of adherence.

Although multiple studies have shown a relationship between treatment adherence and age, with a lower adherence among younger patients (under 45 years of age) because of fertility [21], and the oldest patients (over 65 years of age), because of factors including comorbidities, health-literacy, cognitive function, and lack of social support [22, 23], our results showed that the oldest patients were the most adherent.

Although our study did not find an association between adherence and polypharmacy, regardless of the number of dispensed drugs, the available evidence on this issue is contradictory. In a systematic review assessing adherence to treatment with oral antineoplastic drugs, seven studies showed that polypharmacy was associated with lower adherence, and four concluded the opposite [24]. An explanation for the discrepancy between studies may be the lack of a consensus on the definition of polypharmacy [25]; however, our conclusions were the same regardless of the number of drugs.

However, when analyzing adherence, consideration was not given to the effect of polypharmacy on adherence according to the type of drug. In this regard, patients who use other treatments, such as lipid-lowering and antihypertensive drugs, can be more adherent, presenting greater adherence to HT. This is consistent with other studies that have also concluded that the simultaneous use of multiple chronic drugs for cardiovascular disease is associated with greater adherence to treatment for chronic myeloid leukemia [26]. Emotional distress and psychiatric symptoms, such as depression, anxiety, and post-traumatic stress disorder, frequently occur in BC patients and are associated with a worse quality of life and outcomes in the different treatments [27]. Therefore, the treatment used for these conditions may be associated with lower adherence. In fact, the frequent use of psychotropic drugs is associated with lower adherence to HT. Mental illness is a known risk factor for non-adherence to medical treatment, and consequently poor disease control [28]. In particular, depression and anxiety are strong predictors for poor adherence to HT in BC patients [29].

There are various studies on the influence of living with a partner on the patient’s treatment adherence. Some studies conclude that such fact contributes to greater adherence [30, 31], but there are also studies with the opposite conclusion [7, 32]. The present study found no significant difference in adherence to treatment between those who lived with a partner and those who were divorced, widowed, or single. In our study, no association was observed between educational level and treatment adherence. While a higher educational level is usually linked to greater adherence due to increased awareness of treatment importance and better understanding of instructions provided by the medical team; enhanced ability to comprehend complex medical information and improved communication skills with the medical team, enabling asking questions and resolving doubts; it is important to consider that these associations are not absolute, and treatment adherence is a multifactorial issue influenced by various factors such as social support, cultural beliefs, and personal circumstances. The same result was obtained when comparing patients from Montevideo to those from the country’s interior. Thus, there are no cultural differences between the two environments nor difficulty in accessing means of transportation, although, in this regard, the geographical dimension of the country should be considered, which is negligible in South America. As for the association between adherence to treatment and tumor stage, our study found no such association, although a significant association between the two has been reported, with greater adherence in patients with more advanced tumors [20, 30].

Our results clearly show that adherence to HT is suboptimal in patients diagnosed with early BC treated at the Breast Health Unit of the Hospital de Clinicas, although such treatment is provided free of charge, easy to administer, and generally well tolerated. However, it should be noted that our results are similar and even superior to those reported in various international studies.

This study emphasizes the need to develop interventions to improve the adherence rate. Some actions are very simple but no less important, such as reminder text messages or phone calls to patients, paying particular attention to cases in which they fail to attend the consultation or take excessive time before doing so [32, 33].

Although our study did not reveal significant correlations with specific factors expected to influence adherence (marital status, extent of injury), this is probably due to the relatively small sample size, thereby not providing sufficiently strong conclusions.

The strengths of this study include the population-based design that includes all patients who were treated at the Breast Health Unit of the Oncology Service of the Hospital de Clinicas, Uruguay; that is, patients treated in routine clinical practice are represented.

However, when interpreting the study results, it should be considered that there is no standard for assessing adherence and that the only way to ensure adherence is to confirm that the patient takes the drug. For this reason, our study estimated adherence with subjective data provided by the patients using the Morisky-Green questionnaire combined with the measurement of MPR, an objective criterion. In this regard, although neither dispensing the drug nor attending the consultation guarantees that the patient takes the drug, we consider it unlikely that patients continued to attend consultations, requesting prescriptions, and collecting the drug if they did not intend to use it. Another aspect to consider is volunteer bias, when a particular sample contains only those participants who are actually willing to participate in the study.

When interpreting the obtained results, it should be kept in mind that the survey was performed on patients assisted at the Breast Health Unit of the Oncology Service of the Hospital de Clinicas, which could have introduced biases, and consequently limits the possibility of extrapolating the results to the general population. Therefore, further studies to assess adherence to HT in routine clinical practice including patients assisted in private institutions and from the interior of the country, are required.

Finally, this is a retrospective study, so the groups were not prospectively randomized.

Our results were similar and even superior to those reported in various clinical studies. However, 19.0% of the patients did not adhere to the treatment, despite the known benefits on DFS and OS, being a well-tolerated treatment, and being provided free of charge, since Uruguay has achieved universal health coverage for its entire population.

The current study sheds light on adherence to adjuvant hormonal therapy among women with BC in routine clinical practice in our country.

Finally, the need for the medical oncologist to create awareness among patients about the consequences of treatment non-adherence should be emphasized. This implies adequate advice on how to conduct the treatment and the intervals at which the drugs should be taken since all these correlate with the best possible outcomes. Future studies should be designed to identify patients with risk for non-adherence and conduct timely interventions to maintain and improve adherence.

Our study assessed adherence to HT in patients diagnosed with early BC who were treated at the Breast Health Unit of the Hospital de Clinicas. The results were similar and even superior to those reported in multiple prior studies. However, 19.0% of the patients did not adhere to the treatment, despite the known DFS and OS benefits, being a well-tolerated treatment, and provided free of charge. The most adherent patients were the oldest. We should further investigate the reasons for treatment discontinuation, identify patients at risk of discontinuing, and expand our efforts to improve adherence. It is particularly important to provide the most accurate explanation possible to patients, so they can understand the undeniable benefits of treatment adherence beyond the adverse effects, which are less significant than the benefits. The benefits are more evident in patients who are reluctant to continue treatment regularly. The present study is expected to increase awareness about the importance of investigating adherence to HT in routine clinical practice, thereby improving the quality of care and, consequently, survival.

Acknowledgments

We thank the patients who agreed to respond to our adherence questionnaire and the oncology residents who helped distribute the adherence questionnaire.

Financial Disclosure

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

The authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

Informed Consent

Informed consent was obtained.

Author Contributions

NC, CC, AB, PE, MC and GK contributed to the conception and design of the work. NC, CC, CT, NS, SP, GH and NR did the analysis of data and the draft of the article. MC and GK critically revised the article. All authors were responsible for the acquisition of the data and approved the final version of the article.

Data Availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341-1352.
   doi pubmed
2. Partridge AH, Wang PS, Winer EP, Avorn J. Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol. 2003;21(4):602-606.
   doi pubmed
3. Barron TI, Connolly R, Bennett K, Feely J, Kennedy MJ. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer. 2007;109(5):832-839.
   doi pubmed
4. McCowan C, Shearer J, Donnan PT, Dewar JA, Crilly M, Thompson AM, Fahey TP. Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer. Br J Cancer. 2008;99(11):1763-1768.
   doi pubmed pmc
5. Owusu C, Buist DS, Field TS, Lash TL, Thwin SS, Geiger AM, Quinn VP, et al. Predictors of tamoxifen discontinuation among older women with estrogen receptor-positive breast cancer. J Clin Oncol. 2008;26(4):549-555.
   doi pubmed
6. Partridge AH, LaFountain A, Mayer E, Taylor BS, Winer E, Asnis-Alibozek A. Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol. 2008;26(4):556-562.
   doi pubmed
7. Hagen KB, Aas T, Kvaloy JT, Soiland H, Lind R. Adherence to adjuvant endocrine therapy in postmenopausal breast cancer patients: A 5-year prospective study. Breast. 2019;44:52-58.
   doi pubmed
8. Robinson B, Dijkstra B, Davey V, Tomlinson S, Frampton C. Adherence to adjuvant endocrine therapy in Christchurch women with early breast cancer. Clin Oncol (R Coll Radiol). 2018;30(1):e9-e15.
   doi pubmed
9. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134(2):459-478.
   doi pubmed pmc
10. Yussof I, Mohd Tahir NA, Hatah E, Mohamed Shah N. Factors influencing five-year adherence to adjuvant endocrine therapy in breast cancer patients: A systematic review. Breast. 2022;62:22-35.
    doi pubmed pmc
11. Karve S, Cleves MA, Helm M, Hudson TJ, West DS, Martin BC. Good and poor adherence: optimal cut-point for adherence measures using administrative claims data. Curr Med Res Opin. 2009;25(9):2303-2310.
    doi pubmed
12. Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986;24(1):67-74.
    doi pubmed
13. Grimmsmann T, Himmel W. Polypharmacy in primary care practices: an analysis using a large health insurance database. Pharmacoepidemiol Drug Saf. 2009;18(12):1206-1213.
    doi pubmed
14. Linjakumpu T, Hartikainen S, Klaukka T, Veijola J, Kivela SL, Isoaho R. Use of medications and polypharmacy are increasing among the elderly. J Clin Epidemiol. 2002;55(8):809-817.
    doi pubmed
15. Macari A, Soberanis-Pina P, Varela-Santoyo E, Valle-Sanchez MA, Leal-Hidalgo JL, Torres-Guillen VM, Motola-Kuba D, et al. Prevalence and molecular profile of breast carcinoma using immunohistochemistry markers in Mexican women. World J Oncol. 2021;12(4):119-123.
    doi pubmed pmc
16. Copeland J, Oyedeji A, Powell N, Cherian CJ, Tokumaru Y, Murthy V, Takabe K, et al. Breast cancer in Jamaica: stage, grade and molecular subtype distributions across age blocks, the implications for screening and treatment. World J Oncol. 2021;12(4):93-103.
    doi pubmed pmc
17. Camejo-Martinez N, Castillo-Leska C, Artagaveytia-Coppola NA, Hernandez-Ibero AL, Amarillo-Hernandez DL, Apud-Yumati PS, Melo-Ramundo F, et al. [Adherence to adjuvant hormonal therapy in patients with breast cancer]. Rev Med Inst Mex Seguro Soc. 2019;57(6):357-363.
    pubmed
18. Chirgwin JH, Giobbie-Hurder A, Coates AS, Price KN, Ejlertsen B, Debled M, Gelber RD, et al. Treatment adherence and its impact on disease-free survival in the breast international Group 1-98 trial of tamoxifen and letrozole, alone and in sequence. J Clin Oncol. 2016;34(21):2452-2459.
    doi pubmed pmc
19. Hershman DL, Shao T, Kushi LH, Buono D, Tsai WY, Fehrenbacher L, Kwan M, et al. Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat. 2011;126(2):529-537.
    doi pubmed pmc
20. Hershman DL, Kushi LH, Shao T, Buono D, Kershenbaum A, Tsai WY, Fehrenbacher L, et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. 2010;28(27):4120-4128.
    doi pubmed pmc
21. Llarena NC, Estevez SL, Tucker SL, Jeruss JS. Impact of fertility concerns on tamoxifen initiation and persistence. J Natl Cancer Inst. 2015;107(10):djv202.
    doi pubmed pmc
22. Gellad WF, Grenard JL, Marcum ZA. A systematic review of barriers to medication adherence in the elderly: looking beyond cost and regimen complexity. Am J Geriatr Pharmacother. 2011;9(1):11-23.
    doi pubmed pmc
23. Jacob L, Hadji P, Kostev K. Age-related differences in persistence in women with breast cancer treated with tamoxifen or aromatase inhibitors in Germany. J Geriatr Oncol. 2016;7(3):169-175.
    doi pubmed
24. Greer JA, Amoyal N, Nisotel L, Fishbein JN, MacDonald J, Stagl J, Lennes I, et al. A systematic review of adherence to oral antineoplastic therapies. Oncologist. 2016;21(3):354-376.
    doi pubmed pmc
25. Hughes CM, Cooper JA, Ryan C. Going beyond the numbers - a call to redefine polypharmacy. Br J Clin Pharmacol. 2014;77(6):915-916.
    doi pubmed pmc
26. Efficace F, Baccarani M, Rosti G, Cottone F, Castagnetti F, Breccia M, Alimena G, et al. Investigating factors associated with adherence behaviour in patients with chronic myeloid leukemia: an observational patient-centered outcome study. Br J Cancer. 2012;107(6):904-909.
    doi pubmed pmc
27. Mehnert A, Koch U. Psychological comorbidity and health-related quality of life and its association with awareness, utilization, and need for psychosocial support in a cancer register-based sample of long-term breast cancer survivors. J Psychosom Res. 2008;64(4):383-391.
    doi pubmed
28. Grenard JL, Munjas BA, Adams JL, Suttorp M, Maglione M, McGlynn EA, Gellad WF. Depression and medication adherence in the treatment of chronic diseases in the United States: a meta-analysis. J Gen Intern Med. 2011;26(10):1175-1182.
    doi pubmed pmc
29. Stanton AL, Petrie KJ, Partridge AH. Contributors to nonadherence and nonpersistence with endocrine therapy in breast cancer survivors recruited from an online research registry. Breast Cancer Res Treat. 2014;145(2):525-534.
    doi pubmed
30. Wigertz A, Ahlgren J, Holmqvist M, Fornander T, Adolfsson J, Lindman H, Bergkvist L, et al. Adherence and discontinuation of adjuvant hormonal therapy in breast cancer patients: a population-based study. Breast Cancer Res Treat. 2012;133(1):367-373.
    doi pubmed
31. Pourcelot C, Orillard E, Nallet G, Dirand C, Billion-Rey F, Barbier G, Chouk S, et al. Adjuvant hormonal therapy for early breast cancer: an epidemiologic study of medication adherence. Breast Cancer Res Treat. 2018;169(1):153-162.
    doi pubmed
32. Paladino AJ, Anderson JN, Krukowski RA, Waters T, Kocak M, Graff C, Blue R, et al. THRIVE study protocol: a randomized controlled trial evaluating a web-based app and tailored messages to improve adherence to adjuvant endocrine therapy among women with breast cancer. BMC Health Serv Res. 2019;19(1):977.
    doi pubmed pmc
33. Shelby RA, Dorfman CS, Bosworth HB, Keefe F, Sutton L, Owen L, Corsino L, et al. Testing a behavioral intervention to improve adherence to adjuvant endocrine therapy (AET). Contemp Clin Trials. 2019;76:120-131.
    doi pubmed pmc

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

World Journal of Oncology is published by Elmer Press Inc.