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Int J Clin Pharm (2014) 36:4554

DOI 10.1007/s11096-013-9833-5

REVIEW ARTICLE

Adherence and discontinuation of oral hormonal therapy


in patients with hormone receptor positive breast cancer
Lorena Rocha Ayres Andre de Oliveira Baldoni
Anna Paula de Sa Borges Leonardo Regis Leira Pereira

Received: 23 October 2012 / Accepted: 27 July 2013 / Published online: 11 August 2013
 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2013

Abstract Background Oral treatment in women with longitudinal studies was found. In addition, there was a
breast cancer has been increasingly used. However, a high prevalence of studies using a database (70.8 %).
potentially negative side of oral medication is poor patient Among some of the studies, it was shown that patient
adherence and/or discontinuation, which reduces the adherence to hormonal therapy gradually reduces, while
treatment effectiveness, accelerating progression of the discontinuation increases during the treatment. Conclu-
disease and reducing the patient survival rate. Aim of the sions It was observed a great diversity among rates of
review To compare the rates of adherence and/or discon- adherence and/or discontinuation of hormonal therapy for
tinuation and the methodologies used to assess these out- breast cancer, which may be due to a lack of methodology
comes. It was conducted an integrative review of original standardization. Therefore, adequate and validated meth-
articles published from 2000 to 2012, in which their pri- ods to ensure reliability of the results and allow comparison
mary outcome was to quantify medication adherence and/ in the literature are needed. Furthermore, adherence
or discontinuation of oral hormonal therapy in patients with decreases and discontinuation increases over time, sug-
hormone receptor positive breast cancer. Methods Original gesting the need for patient continuous education and a
studies were searched in the PubMed/MEDLINE, Scopus, pharmacotherapeutic follow up by health professionals to
Embase and SciELO databases. The Medical Subject improve these clinical outcomes.
Heading was used to define descriptors. The descriptor
breast neoplasms was used in all combinations. Each of Keywords Aromatase inhibitors  Breast cancer 
the descriptors medication adherence and patient Hormonal therapy  Medication adherence 
compliance were combined with each of the following Tamoxifen
descriptors tamoxifen, aromatase inhibitors, selec-
tive estrogen receptor modulators, or the terms letroz-
ole, anastrozole, and exemestane. Results Twenty- Impacts on practice
four original articles were included. Our study showed a
wide range of adherence and discontinuation rates, ranging According to literature, there seems to be a wide vari-
from 4595.7 and 1273 %, respectively. Regarding the ation in adherence and/or discontinuation rates to hor-
methodological development of the selected articles, a high monal therapy in patients with breast cancer.
prevalence (87.5 %) of prospective and/or retrospective To ensure reliability of the results, adequate and
validated methods should be used to assess adherence
and/or discontinuation rates to hormonal therapy in
L. R. Ayres (&)  A. de O. Baldoni 
A. P. de Sa. Borges  L. R. L. Pereira patients with breast cancer.
Departamento de Ciencias Farmaceuticas, Faculdade de Ciencias Patients adherence to hormonal therapy gradually
Farmaceuticas de Ribeirao Preto, Centro de Pesquisa em reduces, while discontinuation increases during the
Assistencia Farmaceutica e Farmacia Clnica (CPAFF),
treatment suggesting that a follow up by health
Universidade de Sao Paulo, Avenida do Cafe, s/no., Campus
Universitario da USP, Ribeirao Preto, SP 14040-903, Brazil professionals can be an interesting strategy to improve
e-mail: lorenaayres@hotmail.com the outcomes.

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46 Int J Clin Pharm (2014) 36:4554

Introduction as well as the methodologies employed to assess adherence


and/or discontinuation rates are scarce [19, 20]. Therefore,
Nowadays, it is estimated that each year more than one studies that address this subject are important as they are
million women are diagnosed with breast cancer world- able to identify possible problems and to suggest measures
wide, and more than 410,000 die from the disease [1]. to promote and improve adherence to medication.
However, improvements in early diagnosis and correct
treatment have significantly increased the survival of these
women [2]. Aim of the review
The prognosis and the choice of the most appropriate
treatment are usually based on tumor stage, which consists To quantify and compare the rates of adherence and/or
of surgery for tumor removal followed by radiotherapy, discontinuation and the methodologies used to assess oral
chemotherapy and/or adjuvant therapy with targeted ther- hormonal therapy in patients with hormone receptor posi-
apies that confer fewer systemic cytotoxic side effects [3]. tive breast cancer.
Over expression of HER2/neu and hormone receptors sta-
tus are important factors used in the decision-making
process of the adequate targeted therapy. The humanized
Methods
monoclonal antibody trastuzumab and oral endocrine
therapy are examples of targeted therapies for HER2
A literature review was performed of original articles
positive breast cancer and for breast cancer with the pres-
published between 2000 and 2012.
ence of hormone receptors such as estrogen and proges-
terone receptors, respectively [4].
Search strategy
The main classes of oral endocrine therapy are aroma-
tase inhibitors (AI) (letrozole, anastrozole and exemestane)
We searched PubMed/MEDLINE, Scopus, Embase and
and selective estrogen receptor modulators (SERMs) such
SciELO databases, using Medical Subject Heading
as tamoxifen [5]. According to the Early Breast Cancer
(MeSH) to define descriptors. The descriptor breast neo-
Trialists Collaborative Group [6], adjuvant treatment with
plasms was used in all combinations. Each of the
tamoxifen for 5 years reduces the risk of disease recurrence
descriptors medication adherence and patient compli-
by 41 % and of death by 34 % in women with estrogen
ance were combined with each of the following descrip-
receptor-positive early stage breast cancer.
tors tamoxifen, aromatase inhibitors, selective
During recent decades, a five-year treatment with
estrogen receptor modulators, or the terms letrozole,
tamoxifen represented the standard therapy for women
anastrozole, and exemestane. The connector AND
with estrogen receptor-positive breast cancer. Recently,
was used between terms, according to the example: breast
therapy with AI showed further reduction of the risk of
neoplasm AND medication adherence AND tamoxi-
recurrence and death in postmenopausal women [7, 8]. AI
fen. The limits established were publications between
suppresses only the estrogen production amounts of
January 01, 2000 and December 31, 2012 and in English,
peripheral tissues while in premenopausal women its major
Spanish or Portuguese languages.
production site is the ovary [9]. Although generally well
An integrative review was conducted since it allows the
tolerated, side effects associated with tamoxifen and AI
inclusion of diverse methodologies, such as experimental
such as hot flushes, sleep disturbances, and depression were
and non-experimental studies, whereas the systematic
identified as significant causes for discontinuation and/or
review is focused primarily on experimental studies [21, 22].
non-adherence to treatment [1012].
Therefore, a potentially negative side of oral medication
is poor patient adherence and/or discontinuation, which Inclusion and exclusion criteria
reduces the treatment effectiveness, accelerating progres-
sion of the disease and reducing the patient survival rate The articles were identified and all duplicate records were
[13]. However, oral treatment in women with breast cancer excluded in the first stage. In the second stage, a prior
has been increasingly used due to a reduced prevalence of reading of the title and abstract was conducted to include
side effects compared to chemotherapy, an increased con- original articles in which their main objective was to
venience of drug administration and a decreased hospital- evaluate the rates of adherence to or discontinuation of oral
ization length [14]. medication in patients with hormone receptor positive
Although there are some studies evaluating adherence breast cancer in clinical practice. Therefore, original arti-
and/or discontinuation of hormonal therapy [1518], works cles related to breast cancer chemoprevention, metastatic
that compare the data obtained from these different studies, breast cancer patients since their awareness of the

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Int J Clin Pharm (2014) 36:4554 47

consequences of not taking their medication is higher and Records identified through
they also use different treatment protocols, breast cancer in database searching
males, extended hormonal therapy, and clinical trials, were (n =1024)
excluded, as well as those published as a review, note,
correspondence, editorial, and letter. In the last stage, the Duplicates removed
selected articles were read in their entirety in order to be (n =720)
included.

Records screened
Data analysis (n =304)

The selected articles were subjected to a complete analyt- Records excluded according to
ical reading to identify variables of interest: drug used, the exclusion criteria
sample size, patient age, disease stage, follow up length, (n = 273)

study design, source, method and adherence and/or dis-


continuation rates. These datas were collected and arranged Full-text articles
in a table. Full reading of the articles and variables results assessed for eligibility
were analyzed and performed by three of the authors of this (n =31) Full-text articles excluded, with
reasons
study. In the event of any disagreement, discussions con- (n =7)
tinued until consensus was reached.
Articles, which adherence
and/or discontinuation of
Adherence and discontinuation definitions the hormonotherapy in
breast cancer were not the
main outcome (n=3)
Patients are considered to be adherent when they follow the Studies included in Clinical Trial (n=1)
prescription guidelines correctly, in acting co-responsibly
qualitative synthesis Included patients from a
(n =24) clinical trial (n=1)
towards their treatment [23]. Compliance refers to the Included patients with
patients obedience in following the prescription and metastatic breast cancer
(n=2)
guidelines made by the physician [24]. In order to stan-
dardize the terms used in the article, we decided to use the Fig. 1 Selection of the articles for the integrative review adapted
term adherence to refer to adherence and/or compliance. from PRISMA flow diagram [27]
Discontinuation occurs when the patient stops taking the
prescribed medication for a reason and it is also defined by Among them, nine referred only to adherence, ten only
a lapse in treatment longer than a determined amount of to discontinuation and five to adherence and discontinua-
time, which may vary from 45 to 180 days in some studies tion (Table 1). In addition, 13 articles addressed the use of
[25, 26]. In this case it is not considered as non-adherence, tamoxifen, three of AI and eight of both.
but as a decision to discontinue following poor response to The rates of adherence in cancer patients ranged from 45
the drug or as a result of adverse side effects, intolerance to to 93.4 % among studies with tamoxifen (n = 7), from 62
the drug, difficult access to medicines, employment and to 94.7 % with AI (n = 3) and from 49 to 95.7 % with both
socioeconomic status, social stigma of disease, and cog- (n = 4). The rates of discontinuation ranged from 15 to
nitive function [25]. Persistence is the length of time 60 % in studies with tamoxifen (n = 9), 18.924.7 % with
between the beginning of the treatment until the last dose, AI (n = 3) and 1273 % with both (n = 7). The same
which immediately precedes discontinuation [26]. The study may have been counted more than once since some
term discontinuation was used in this review since it was of them analyzed adherence and/or discontinuation of
the term used in the investigated studies. tamoxifen and AI separately.
Regarding the methodological development of the
selected articles, table 1 shows a high number (87.5 %) of
Results prospective and/or retrospective longitudinal studies, and
identified only two cross-sectional studies [11, 41]. In
We identified 1,024 studies, of which 24 were included in addition, seven studies used self-report (n = 1) [40] and
this study (Fig. 1). All the articles that were in accordance interviews (n = 6) [1012, 17, 41, 42] to access adherence
with our inclusion criteria were available as full text and all and/or discontinuation and the majority of them (n = 18)
the included studies were published in English and con- used the information provided by professional routine
ducted in developed countries. databases, which includes medical records and registers of

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48

Table 1 Published articles evaluating adherence and/or discontinuation during hormonal therapy for breast cancer
Reference, year Drug(s) Subjects Number Age (years) Disease Stage Follow-up Study design Method of evaluation adherence Adherence (A) or
of publication and length (A) or discontinuation (D) Discontinuation (D)

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country

Font et al. [17], Tamoxifen and 692 B49 years; IIIIa stage 5 years Retrospective Physician report and A: Questionnaire: 92 %
Spain AI 5074 years; cohort questionnaire (A) (tamoxifen: 88.8 %; IA: 92.6;
Refill prescription Tamoxifen ? IA: 93.8)
C75 years
(D = coverage of prescribed Physician report: 94.7 %
medication less than 80 %) (tamoxifen: 93.4 %; IA: 94.7;
tamoxifen ? IA: 95.7)
D: 25.3 % (tamoxifen: 31.4 %;
IA: 24.5; tamoxifen ? IA:
21.5)
Huiart et al. [18], Tamoxifen 246 39.6 mean IIII stage Median Prospective MPR (D = gap of more than A (first year) = 93.9 %
France 2 years cohort 90 days) D: 1st year = 17 %
(1.03.3)
2nd year = 29.7 %
3rd year = 39.5 %
Wigertz et al. Tamoxifen and 1,741 \40 years IIII stage 3 years Prospective MPR (D = gap of more than A = 69 %
[28], Sweden AI 4049 cohort 180 days) D = 12 %
5059
6069
7079
C80
Cluze et al. [29], Tamoxifen and 196 37 mean IIII stage 2 years Prospective Pharmacy refill data (D = at D = 42 %
France AI cohort least two consecutive months
of interruption)
Hershman et al. Tamoxifen and 8,769 \50 IIII stage 4 1/2 year Prospective MPR A 4 1/2 year = 49 %
[30], USA AI 5064 cohort
C65
Huiart et al. [31], Tamoxifen and Total 13,479 62.0 mean IIII stage 5 years Prospective MPR (D = gap of 90 days or D = 29.8 %
UK AI Tamoxifen (Tamoxifen) cohort more) Tamoxifen
10,806 70.8 mean D = 31 %
AI 2,673 (AI)
AI
D = 18.9 %
Nekhlyudov et al. Tamoxifen and 2,207 [18 years Early stage Median Prospective MPR (D = gap of more than D: 2173 %
[32], USA AI 923 days cohort 60 days) 1st year = 21 %
2nd year = 30 %
3rd year = 38 %
4th year = 47 %
5st year = 73 %
Int J Clin Pharm (2014) 36:4554
Table 1 continued
Reference, year Drug(s) Subjects Number Age (years) Disease Stage Follow-up Study design Method of evaluation adherence Adherence (A) or
of publication and length (A) or discontinuation (D) Discontinuation (D)
country

Neugut et al. [33], AI 8,110 [50 years Early stage 2 years Retrospective MPR (D = gap of more than A = \65 years: 89.7 %;
USA (\ 65 years); cohort 45 days) C65 years: 91.1.
14,050 D: \65 years: 21 %; C65 years:
(C 65 years) 24.7 %
Sedjo et al. [34], AI 13,593 55.5 mean Primary and 1 year Retrospective MPR A = 77 %
Int J Clin Pharm (2014) 36:4554

USA secondary cohort


breast cancer
Thompson et al. Tamoxifen Cohort 1: 391 Cohort 1: IIII stage Not Retrospective MPR A = 85.6 %
[9], UK Cohort 2: 227 60.5 mean available cohort
Cohort 2:
63.1 mean
Dezentje et al. Tamoxifen 1,962 59.6 mean IIII stage 1 year Retrospective MPR A 1st year = 93 %
[35], cohort A 3rd year = 84 %
Netherlands
Van Herk-Sukel Tamoxifenand 4,917 B35 to C70 IIIIa stage 5 years Retrospective Medication count (D = gap of Tamoxifen:
et al. [36], AI cohort more than 60 days) D 1st year = 17 %
Netherlands
D 2nd year = 30 %
D 3rd year = 45 %
D 4th year = 50 %
D 5th year = 60 %
Tamoxifen/IA:
D 1st year = 13 %
D 2nd year = 22 %
D 3rd year = 31 %
D 4th year = 37 %
D 5th year = 51 %
Kimmick et al. Tamoxifen and 1,491 67 median Nonmetastatic 2 years Not available MPR (D = gap of more than A = 60 %
[37], USA AI 90 days) D = 20 %
Ma et al. [38], Tamoxifen 788 5459 Not available 5 years Retrospective Database (A = not follow A = 63 %
USA cohort physician recommendation)
Owusu et al. [16], Tamoxifen 961 [65 IIIb stage 5 years Prospective Medical record (D = gap of D = 46 %
USA cohort more than 60 days)
Partridge et al. Anastrozole 7,132 [35 to [65 Early-stage 3 years Retrospective MPR A 1st year = 7886 %
[15], USA cohort A 3rd year = 6279 %
Barron et al. [39], Tamoxifen 2,816 [35 Not available 3.5 years Retrospective Medical record (D = gap of D 1st year = 22.1 %
Ireland cohort more than 180 days) D 3.5 years = 35.2 %
49

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50

Table 1 continued
Reference, year Drug(s) Subjects Number Age (years) Disease Stage Follow-up Study design Method of evaluation adherence Adherence (A) or
of publication and length (A) or discontinuation (D) Discontinuation (D)

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country

Kahn et al. [40], Tamoxifen 881 \50 to [65 IIIIa stage 4 years Prospective Self-report (D = Stop taking D = 21 %
USA cohort medication after 4 years)
Atkins et al. [41], Tamoxifen 72 59.4 mean Stable disease Cross Interview A = 45 %
UK sectional
Lash et al. [12], Tamoxifen 462 [65 IIIIa Stage 5 years Ambispective Interview (D = stop taking D 5th year = 31 %
USA cohort medication)
Grunfeld et al. Tamoxifen 110 56.3 mean Primary breast Cross Interview [A = Medication A = 88 %
[11], UK cancer sectional Adherence Report Scale
(MARS-5)]
Fink et al. [42], Tamoxifen 516 [65 IIIIa stage 2 years Prospective Interview (D = stop taking D 2nd year = 17 %
USA cohort medication) D 2 1/4 year = 21 %
Partridge et al. Tamoxifen 2,378 75.4 mean Early-stage 4 years Retrospective MPR A = 77 %
[43], USA cohort A 1st year = 83 %
A 2nd year = 68 %
A 3rd year = 61 %
A 4th year = 50 %
Demissie et al. Tamoxifen 189 67.7 mean III stage 3 years Ambispective Interview (D = stop taking D = 15 %
[10], USA cohort medication)
AI aromatase inhibitors, MPR Medication Possession Ratio (less than 80 % of days covered was defined as nonadherence)
Int J Clin Pharm (2014) 36:4554
Int J Clin Pharm (2014) 36:4554 51

Medication Possession Ratio (MPR) and pharmacy refill possible to observe that patients with cancer, taking hor-
data. One study used both, database and interviews to monal therapy, seem to have better adherence to treatment
collect data. Only one study described the use of a specific compared to patients with other chronic diseases, which is
and validated instrument (Medication Adherence Report approximately 50 % in developed countries for the chronic
Scale MARS-5) [11]. None of the studies used direct patients [23]. One explanation for this can be that patients
methods, such as quantification of the concentration of the with cancer have a better understanding of the risks of not
drug or metabolite in plasma or urine and quantification of properly taking the drugs [44, 45].
biological markers to estimate adherence and/or discon- Another review found rates of adherence and discon-
tinuation rates. tinuation in agreement with ours, ranging from 41 to 72 %
Considering the definition of adherence and discontin- and from 31 to 73 %, respectively [20]. That study was
uation, ten studies evaluated adherence using MPR, which conducted in a similar period of time, from 1998 to May
defined nonadherence as a less than 80 % of days covered 2012, while ours was from January 2000 to December
by the medication [9, 15, 18, 28, 30, 3335, 37, 43]. Dis- 2012. The study included 30 articles and from the 24
continuation was defined by a lapse in treatment, which selected articles in our review, there were 21 matches with
may vary from 45 to 180 days in seven studies using MPR those included in that review. The contrast found between
[18, 28, 3133, 36, 37]. Three studies that used interviews the numbers of articles selected in both reviews was due to
and one that used self-report considered discontinuation distinct inclusion criteria, limits, terms to identify the
when a patient stops taking the medication [10, 12, 40, 42]. articles and mainly because different databases were
In relation to the studies that used self-report and searched.
interviews, 72881 patients were investigated, while those An interesting finding related to the years of publication
using professional routine database could include a greater is that from 2000 to 2007, studies were exclusively per-
number of patients, as observed in two studies that included formed with tamoxifen in a clinical setting. This happened
more than 13,000 women. because the first AI to be approved by the Federal Drug
It is worth mentioning that the age range for all the Administration (FDA) was anastrozole in 2002, as an
studies varied from 18 to more than 80 years. The way age adjuvant treatment for postmenopausal women [46, 47].
was arranged did not allow calculating a mean age for all Evaluation of its use takes at least 5 years as this is the
the studies. However the majority of patients were from 50 standard period of treatment, therefore, the first study with
to 70 years. anastrozole was from 2008.
Considering the follow-up length of the longitudinal All the selected articles in our study were originally
studies, it ranged from 1 to 5 years, with a mean of from developed countries where it seems to have higher
3.3 years. Three studies compared adherence rates adherence rates compared to emerging countries [23].
throughout time [15, 35, 43]. All of them showed a However, even with the socioeconomic similarity, hetero-
reduction in adherence rates over the years. Moreover, five geneity in adherence rates occurred. The causes of non-
studies compared the discontinuation rates in the same way adherence are multifactorial and may be related to
and all of them showed that discontinuation gradually reduction of care during treatment due to lack of specific
increases throughout the treatment period [18, 32, 36, 39, symptoms or because the patient might experience a cure
42]. sensation of the disease, and adverse reactions that may
Side effects associated with tamoxifen and AI were arise during treatment [48]. One of the reasons of the
identified as significant causes for discontinuation and/or heterogeneity observed among the rates of nonadherence
non-adherence to treatment among three of the selected and/or discontinuation seems to be due to the period of
articles [10, 12, 29]. However the studies did not compare treatment when data collection was performed, since
the side effect profiles of tamoxifen and AI have on patients seem to be more adherent at the beginning of
patients behavior. treatment.
The length of follow up is relevant because according to
the Early Breast Cancer Trials Collaborative Group [6],
Discussion 5 years of tamoxifen treatment is a major factor in the
reduced mortality rate from early stage breast cancer. In
Our review showed that all the studies analyzed are non- addition, the discontinuation and nonadherence to treat-
experimental and that they present a wide range of adher- ment can lead to breast cancer recurrence, disease pro-
ence and discontinuation rates, ranging from 4595.7 and gression, such as the development of metastasis, which
1273 %, respectively. However only three studies showed may be related to an increased consumption of health
adherence rates below 60 % [30, 41, 43]. Analyzing the resources, including an increased number of physician
incidence and/or prevalence of adherence in this study it is visits, higher hospitalization rates and longer hospital stays

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52 Int J Clin Pharm (2014) 36:4554

[15, 48]. Moreover, as observed in longitudinal studies, it is majority of studies used database or medical records as
noteworthy that patient adherence to hormonal therapy data sources, which can overestimate the adherence rates,
gradually reduces [15, 35, 43], while discontinuation since collection of the medication at the pharmacy does not
increases over the years [18, 32, 36, 39, 42]. This suggests guarantee that the patient actually takes their medicine.
the need for pharmacotherapeutic follow up to the patient Considering the MPR, patients might get their medication
during the whole treatment to prevent recurrence and in another pharmacy without computerizing the medication
complications of the disease. in the same database which may underestimate the rates of
adherence and/or discontinuation. In addition, in the liter-
Methods to evaluate rates of adherence and/ ature there is a wide variety of definitions on adherence and
or discontinuation discontinuation and a wide variety of terms that have been
used to describe medication-taking behavior, such as per-
The majority of the articles (87.5 %) used longitudinal sistence, concordance and medication adherence. There-
studies to analyze adherence and/or discontinuation. It is fore there is a need to standardize these definitions to allow
important to note that longitudinal studies provide answers a better comparison among the studies. An European
related to the incidence of adherence and/or discontinua- consensus was elaborated to face this diversity of concepts
tion of medication prescribed during treatment, while and terms and the various problems related to publications
cross-sectional studies allow the assessment of prevalence about adherence [26].
only. Considering the method, it is important to highlight
that MPR was used in 54.2 % of the studies but it was used Suggestion to improve adherence and future
to analyze different variables, since six articles analyzed recommendations
adherence, four adherence and discontinuation, and three
only discontinuation. Patient education by the health care team has shown sig-
Font and colleagues used a combination of methods nificant improvement in adherence in the treatment of
[17], a questionnaire and a physicians report in which rates various diseases and their complications [52]. However
of adherence were 92 and 94.7 %, respectively. By ana- little is known about professionals training, beliefs or
lyzing their refill prescriptions, the problems related to practice in this area [53]. As observed in some studies [15,
adherence were more significant (discontinuation rate of 35, 43], rates of adherence were decreasing gradually over
25.3 %). This difference found justifies the use of different the years, which may be due to a diminished frequency in
instruments to estimate adherence incidence and/or prev- physician visits. As patients have to go to the pharmacy
alence. Besides, this approach reduced the biases inherent often to acquire their drugs, the pharmacists are the health
to each type of methodology [49]. professionals who have more patient contact between the
Seventy-five percent of the studies used a professional physicians visits and as such they are able to remind them
routine database as the data collection source. The use of of the importance of taking their drug as prescribed.
database in research tends to improve health care programs, Therefore, this is a natural opportunity to monitor the
as they provide a broad representation of the sampled progress of therapy [54]. In this context, a service of
population, and facilitate longitudinal studies to be per- continuous patient education provided by pharmacists in
formed in a shorter period of time [50]. This fact can be collaboration with other healthcare professionals can be an
observed in two studies that used professional routine interesting strategy to improve adherence to drug treat-
database as a source of information and could include more ment, as already observed in pharmaceutical care studies
than 13,000 women in contrast with studies that used [5558].
questionnaires and only interviewed 72881 patients.
Despite the advantages of the magnitude of information
received from large databases, it is noteworthy that there Conclusion
are limitations to the analysis and interpretation of results,
because it is difficult to confirm the reliability and validity In this review, we could observe differences among rates of
of the database used [50]. To increase the reliability and adherence and/or discontinuation of hormonal therapy for
validity of data from databases, researchers need to pre- breast cancer, ranging from 45 to 95.7 % and from 12 to
viously select the appropriate database and analyze how 73 %, respectively. This diversity can be justified by data
population data were created or inserted into the database collection performed in different periods of treatment,
[51]. since we could observe that patient adherence to hormonal
This review has some limitations. Firstly, studies that therapy gradually reduces, while discontinuation increases
used self-report (n = 1) and interviews (n = 6) as sources during the treatment. Therefore further studies are impor-
of data collection can lead to recall bias. Secondly, the tant, especially those that compare adherence and/or

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Int J Clin Pharm (2014) 36:4554 53

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Acknowledgments The authors would like to thank the School of 17. Font R, Espinas JA, GilGil M, Barnadas A, Ojeda B, Tusquets I,
Pharmaceutical Sciences of Ribeirao PretoUniversity of Sao Paulo et al. Prescription refill, patient self-report and physician report in
for its support during the research. assessing adherence to oral endocrine therapy in early breast
cancer patients: a retrospective cohort study in Catalonia, Spain.
Funding National Council for Scientific and Technological Br J Cancer. 2012;107(8):124956.
Development (CNPq), Brazil. 18. Huiart L, Bouhnik AD, Rey D, Tarpin C, Cluze C, Bendiane MK,
et al. Early discontinuation of tamoxifen intake in younger
women with breast cancer: is it time to rethink the way it is
Conflicts of interest None to declare.
prescribed? Eur J Cancer. 2012;48(13):193946.
19. Gotay C, Dunn J. Adherence to long-term adjuvant hormonal
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