Skip to main content
NCBI home page
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 2013 Feb 27;139(6):915–923. doi: 10.1007/s00432-013-1402-8

Influence of compliance on bone mineral density changes in postmenopausal women with early breast cancer on Anastrozole

Matthias Kalder 1,✉, Volker Ziller 1, Ioannis Kyvernitakis 1, Dana Knöll 1, Olaf Hars 2, Peyman Hadji 1
PMCID: PMC11824321  PMID: 23443254

Abstract

Purpose

Adjuvant treatment for hormone receptor–positive breast cancer in postmenopausal women with aromatase inhibitors is associated with increased bone loss depending on the compliance to treatment.

Methods

In this bone substudy, bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry at baseline and after 12- and 24-month treatment in 63 patients receiving Anastrozole as adjuvant treatment for hormone receptor–positive early breast cancer. To minimize the effects of confounders, a matched pair analysis (compliant N = 21, non-compliant N = 21) was performed.

Results

Anastrozole treatment in compliant patients leads to a decrease in BMD (g/cm2) at lumbar spine and total hip from baseline to 12 and 24 months (−2.57 % P = 0.004; −2.02 % P = 0.05; −2.57 % P = 0.001 and −4.18 % P = 0.003, respectively) compared to non-compliant patients (−1.71 % P = 0.050; −2.00 % P = 0.085; −1.65 % P = 0.055 and −3.20 % P = 0.005, respectively).

Conclusions

Anastrozole treatment in compliant patients with breast cancer resulted in a larger, increase in bone loss at 12 and 24 months compared to non-compliant patients. Bone loss stabilized in both groups at the spine from 12- to 24-month treatment, whereas maintained at the total hip.

Keywords: Breast cancer, Compliance, Aromatase inhibitor, Bone mineral density, Osteoporosis

Introduction

Several international guidelines for the adjuvant endocrine treatment of postmenopausal women with hormone receptor–positive early breast cancer (BC) have acknowledged the recently reported results of several head-to-head trials leading to a shift from tamoxifen to third-generation aromatase inhibitors (AIs), Anastrozole, exemestane and letrozole (Coates et al. 2007; Coombes et al. 2004, 2007; Eastell et al. 2011; Forbes et al. 2008; Goss et al. 2003, 2005; Howell et al. 2005).

The safety profile of AIs compared to tamoxifen has proven a lower incidence of thromboembolic events and endometrial cancer, but is associated with an increase in of arthralgia/myalgia and bone loss followed by an increased incidence of osteoporosis and fractures risk in postmenopausal women (Coates et al. 2007; Coombes et al. 2004, 2007; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) 2005; Eastell et al. 2011; Goss et al. 2003; Hadji 2009; Love et al. 1992).

Previous studies reported the highest rates of bone loss during the first year of AI treatment with a reduction and stabilization thereafter (Coleman et al. 2007; Eastell et al. 2008). Additionally, it has been shown that bone loss with regard to AIs can be effectively prevented and managed with lifestyle changes, adequate calcium and vitamin D supplementation and the use of bisphosphonates if indicated (Hadji 2008).

With regard to the seriousness of their disease, patients with BC in general are considered as exceedingly motivated and compliant to treatment. In contrast to that assumption, recent studies reported a session of drug intake with regard to tamoxifen as well as AIs in a considerable proportion of patients already during the first year in the course of the 5-year recommended adjuvant treatment. Reported poor tamoxifen adherence was associated with an increased risk of breast cancer recurrence as well as increased mortality (Dezentje et al. 2010; Hershman et al. 2011). Due to a growing number of BC survivors, the emphasis on compliance in the adjuvant treatment settings will increase (Hadji 2010).

While earlier studies on compliance to treatment were mainly focussing on health care data-based analyses, recent studies provide evidence from daily clinical practice at a patient level. In several studies comprising different approaches, it has been shown that less than half of the patients with BC were taking their adjuvant hormonal therapy for the total duration and within an optimum schedule (Fallowfield 2005; Hershman et al. 2010; Murphy et al. 2012; Partridge et al. 2003, 2008; Waterhouse et al. 1993).

Recently, we reported the results of a study designed to investigate self-reported compliance in BC patients on Anastrozole and tamoxifen including prescription refill counts in a real world setting. Within the first 12 months, patients treated with Anastrozole or tamoxifen comprised a considerable decreased adherence rate of 69 versus 80 %, respectively (Ziller et al. 2009). Since compliance has been shown to decrease over time in the clinical practice, the risk of treatment failure is expected to increase (Hadji 2010).

Therefore, this substudy was designed to compare the BMD effects of adjuvant treatment with Anastrozole in postmenopausal women with hormone receptor–positive BC with regard to compliance.

Patients and methods

All patients provided written informed consent before enrolling into the study. The study was approved by the local ethics committees and was conducted in accordance with the Declaration of Helsinki.

Study design

We conducted a randomized, single institution bone substudy of the Compliance in Adjuvant treatment for primary breast cancer study trial that was designed to compare the effects of Anastrozole on BMD in compliant compared to non-compliant postmenopausal women with ER-positive and/or progesterone-positive BC.

Patients diagnosed with hormone receptor–positive primary BC who were recommended an adjuvant treatment with an aromatase inhibitor were eligible for recruitment. Diagnosis and treatment were initiated independently of the study according to German BC guidelines by the interdisciplinary tumor board of the local comprehensive cancer center. Patients were required to have completed primary surgery and/or radiotherapy and/or chemotherapy, if indicated. Measurement of BMD was performed within the hospitalization directly after surgery as well as after 12 and 24 months.

Additionally, patients needed to be capable of using oral medication on their own initiative following prescribing information. Patients continuously hospitalized, staying in nursery home or receive support via an ambulatory home care service or similar were excluded from the study as well as patients suffer from any form of dementia or similar disease with interference of memory and those who were known for medical, drug or alcohol abuse.

Adherence, osteoporosis-related risk factors and clinical signs and symptoms were also evaluated by a specifically designed questionnaire send to the patient at baseline, after 12 and 24 months cross-examined by phone calls after few days (Hadji et al. 2007; Kalder et al. 2011).

A DXA T score >−2.5, abstinence from strenuous exercise and alcohol consumption during the 48-h period before each study visit were also required. The clinical fracture rate was assessed, and any osteoporosis-related fracture would have led to study withdrawal.

Definition of compliance

Compliance is defined as the percentage of a prescribed dose that is correctly taken in a definite time frame. For this study, the adherence after 12 and 24 months after therapy initiation was measured. We distinguished self-reported compliance and prescription refill counts. The prescription refill counts are used to calculate the “Medication Possession Ratio” (MPR) that indicates the quotient of recommended prescriptions to real prescriptions. According to the current literature, patients are classified as compliant if self-reported adherence and MPR of 80 % or more are achieved (Banning 2012; Coombes et al. 2004; Fallowfield 2005; Howell et al. 2005; Murphy et al. 2012; Waterhouse et al. 1993; Ziller et al. 2009).

Bone mineral density measurement

Bone mineral density was assessed at baseline (first prescription indicating the start of therapy) followed by 1 and 2 years within the range of ±3 months using a Prodigy densitometer (GE/Lunar). Assessments of BMD were carried out using DXA imaging at the lumber spine (L1–L4) and total hip. All measurements were performed with the same device and by the same operator to minimize the precision error. The performance characteristics and standardized quality control procedures of these methods and device have been described in detail previously (Blake and Fogelman 1997; Kanis et al. 1996).

Primary end point

The primary end point was change in BMD (g/cm2) on Anastrozole treatment from baseline to 24 months in lumbar spine (L1–L4) for compliant compared to non-compliant patients.

Secondary end points

Secondary end points included the change in BMD (g/cm2) on Anastrozole treatment from baseline to 12 months in lumbar spine (L1–L4) for compliant compared to non-compliant patients, the changes from baseline to 12 and 24 months in the total hip BMD (g/cm2). Furthermore, possible influences of demographic data, baseline characteristics and medical history between compliant and non-compliant patients on changes in BMD were also assessed.

Statistical analysis

SPSS for Windows 20 (SPSS GmbH Software, Munich, Germany) was used for data analysis. A total of 63 assessable patients were included into the bone substudy having a baseline assessment and at least one post-baseline measurement for BMD after 12 and 24 months in our institution (Fig. 1). Results were reported as absolute values of BMD (g/cm2). The demographic data for patients in each group were analyzed for normal distribution (Kolmogorov–Smirnov test) and compared before and after matching for potentially significant confounding variables using the matched-pairs method for age (±10 years), body mass index (±5.0 kg/m2) and BMD of total hip (±0.15 g/cm2). Cases and controls were compared by unpaired two-tailed t test. The Wilcoxon and Mann–Whitney U test were used evaluating group differences, and baseline characteristics were analyzed for normal distribution using χ 2 test and Fisher’s exact test.

Fig. 1.

Fig. 1

Open in a new tab

Study design

Results

Patient characteristics

Altogether 180 patients receiving Anastrozole were randomized from April 2006 to December 2008 into the core study. All patients were offered to participate into the bone substudy. Due to the consent to participate as well as the lack of complete post-baseline measurement of BMD, 117 patients were excluded from the following evaluation. Finally, 63 patients were available for the analysis (compliant N = 42, non-compliant N = 21; Fig. 1). In accordance with our expectation, the Mann–Whitney U test of the mean percentage compliance between compliant and non-compliant patients was highly significant (N = 63, P ≤ 0.001; N = 42, P ≤ 0.001). Cases and controls were compared by unpaired two-tailed t test and showed a significant difference in the sample size of the groups as well as for the total hip (g/cm2). Therefore, a pre-planned matched-pair analysis was performed including 21 non-compliant and an equal number of compliant patients. Patients’ baseline characteristics were well balanced with regard to patient characteristics, tumor-related variables and treatments between the groups (Tables 1, 2).

Table 1.

Baseline characteristics in compliant and non-compliant patients (N = 63) with no significant differences in both groups according to Chi2- and Fishers exact testing

Non-compliant (N = 21) Compliant (N = 42) Total (N = 63) P
Mean SD Mean SD Mean SD
Age (years) 60.9 7.2 63.7 6.9 62.8 7.1 0.113
Weight (kg) 78.2 18.7 74.3 14.8 75.6 16.2 0.362
Height (cm) 163.0 6.9 162.5 6.1 162.7 6.4 0.750
BMI (kg/m2) 29.3 6.3 28.2 5.6 28.5 5.8 0.453
BMD (g/cm2)
 Spine L1–L4 1.05 0.13 1.04 0.16 1.04 0.15 0.780
 Total hip 0.97 0.10 0.89 0.12 0.91 0.12 0.013
N % N % N % P
TNM_T
 T1 16 76.2 28 66.7 44 69.8 0.628
 T2 5 23.8 13 31.0 18 28.6
 T4 0 0.0 1 2.4 1 1.6
 Total 21 100.0 42 100.0 63 100.0
TNM_N
 N0 10 47.6 28 66.7 38 60.3 0.241
 N1 9 42.9 9 21.4 18 28.6
 N2 2 9.5 3 7.1 5 7.9
 N3 0 0.0 2 4.8 2 3.2
 Total 21 100.0 42 100.0 63 100.0
TNM_M
 M0 21 100.0 41 97.6 62 98.4 0.476
 M1 0 0.0 1 2.4 1 1.6
 Total 21 100.0 42 100.0 63 100.0
Receptor status
 Positive 21 100.0 42 100.0 63 100.0 –
 Total 21 100.0 42 100.0 63 100.0
Radiation
 No 0 0.0 1 2.4 1 1.6 0.476
 Yes 21 100.0 41 97.6 62 98.4
 Total 21 100.0 42 100.0 63 100.0
Chemotherapy
 Other 0 0.0 2 4.8 2 3.2 0.470
 Antracyclin 4 19.0 5 11.9 9 14.3
 No 17 81.0 35 83.3 52 82.5
 Total 21 100.0 42 100.0 63 100.0
Surgery
 Breast-conserving 14 66.7 35 83.3 49 77.8 0.134
 Mastectomy 7 33.3 7 16.7 14 22.2
 Total 21 100.0 42 100.0 63 100.0
Open in a new tab

Table 2.

Baseline data for matched pairs in compliant and non-compliant patients (N = 42) with no significant differences in both groups according to t-test for independent samples

Non-compliant (N = 21) Compliant (N = 21) Total (N = 42) P
Mean SD Mean SD Mean SD
Age (years) 60.9 7.2 63.5 8.0 62.2 7.6 0.271
Weight (kg) 78.2 18.7 76.2 15.3 77.2 16.9 0.706
Height (cm) 163.0 6.9 160.8 6.2 161.9 6.6 0.274
BMI (kg/m2) 29.3 6.3 29.5 5.7 29.4 6.0 0.927
L1–L4 (g/cm2) 1.05 0.13 1.09 0.14 1.07 0.14 0.348
Total hip (g/cm2) 0.97 0.10 0.93 0.10 0.95 0.10 0.236
Open in a new tab

Primary end point

The percentage change in BMD (g/cm2) at the lumbar spine (L1–L4) from baseline to 24 months for compliant patients was −2.02 % (P = 0.050) and for non-compliant patients −2.00 % (P = 0.085) (Fig. 2; Table 4). There was no significant difference between compliant and non-compliant patients at 24 months with respect to percentage change in spinal BMD (g/cm2).

Fig. 2.

Fig. 2

Open in a new tab

The percentage changes in bone mineral density (BMD g/c m2) of lumbar spine (L1–L4) and total hip at baseline 12 and 24 months displayed for the matched pairs of compliant, non-compliant and total patients (N = 42)

Table 4.

The percentage changes in bone mineral density (BMD g/cm2) of lumbar spine (L1–L4) and total hip from baseline to 12 and 24 months displayed for the matched pairs of compliant and non-compliant patients (N = 42)

Time in months Compliance
No Yes
% P % P
Lumbar spine L1–L4 (g/cm2) 0–12 −1.71 0.050 −2.57 0.004
0–24 −2.00 0.085 −2.02 0.050
Total hip (g/cm2) 0–12 −1.65 0.055 −2.57 0.001
0–24 −3.20 0.005 −4.18 0.003
Open in a new tab

P values measured according to the Wilcoxon test

Secondary end points

The percentage change in BMD (g/cm2) at the lumbar spine (L1–L4) from baseline to 12 months was significantly different in both groups (−2.57 %, P = 0.004 in the compliant group vs. −1.71 %, P = 0.050 in the non-compliant group, respectively) and indicated a trend between compliant and non-compliant patients (Fig. 2; Table 4).

The percentage change in BMD (g/cm2) at the total hip from baseline was significantly different in compliant patients at 12 months (−2.57; P = 0.001) and continued decreasing significantly at 24 months (−4.18; P = 0.003). Non-compliant patients showed initially a non-significant trend in percentage change from baseline to 12 months in BMD (g/cm2) at the total hip (−1.65; P = 0.055) but continued decreasing significantly at 24 months (−3.20; P = 0.005). There was no significant difference between compliant and non-compliant patients at 12 and 24 months with respect to percentage change in BMD (g/cm2) at the total hip (Fig. 2; Table 4).

The absolute change in BMD (g/cm2) at lumbar spine and total hip with regard to compliant and non-compliant patients at baseline 12 and 24 months is displayed in Table 3. In none of the groups, non-traumatic fractures were recorded at 24 months.

Table 3.

Mean changes (±SD) in bone mineral density (BMD g/cm2) of lumbar spine (L1–L4) and total hip at baseline 12 and 24 months displayed for the matched pairs of compliant and non-compliant patients during therapy (N = 42)

Time in months Compliance
No (N = 21) Yes (N = 21) Total (N = 42)
Mean SD Mean SD Mean SD
Lumbar spine L1–L4 (g/cm2) 0 1.050 0.129 1.091 0.144 1.070 0.137
12 1.032 0.124 1.063 0.143 1.047 0.133
24 1.029 0.138 1.069 0.159 1.049 0.148
Total hip (g/cm2) 0 0.968 0.102 0.930 0.102 0.949 0.103
12 0.952 0.093 0.905 0.109 0.929 0.103
24 0.937 0.088 0.894 0.129 0.916 0.111
Open in a new tab

Discussion

To our knowledge, this current matched-pair controlled bone substudy is the first to investigate the influence of an adjuvant endocrine treatment with an AI on the BMD in compliant postmenopausal women with hormone–positive early BC compared to non-compliant controls. Compliant and non-compliant patients treated with Anastrozole in the presented study have a different mean percentage of BMD with regard to change from baseline to 12 and 24 months at the lumbar spine and the total hip (Table 4). The observed changes in the BMD of the lumbar spine and the total hip corresponded in non-compliant patients to an average bone loss of −1.7 and −1.7 % after 12 months and −2.0 and −3.2 % after 24 months, respectively, compared to an average bone loss of −2.8 and −2.8 % after 12 months and −2.0 and −4.2 % after 24 months in compliant patients, respectively. Although the differences in both groups remained significant at almost all time points, the change of bone loss suggested a stabilization over time.

Bone loss at the lumbar spine and total hip as well as increased fracture risk with regard to AI treatment has been shown in several recent trials (Hadji et al. 2012). The Anastrozole, tamoxifen alone or in combination trial evaluated upfront Anastrozole compared to tamoxifen during a 5-year treatment period. Patients treated with Anastrozole experienced a decrease in BMD from baseline to 60 months at the lumbar spine and at the total hip (−6.1 and −7.2 %, respectively) as well as a statistically significantly increased rate of fractures (11.0 %). The same association of BMD loss and increased fracture risk could be seen with regard to studies using the non-steroidal AI letrozole as well as the steroidal AI exemestane (Coates et al. 2007; Coombes et al. 2007; Eastell et al. 2008; Howell et al. 2005).

Similar results have been reported in a meta-analysis of the US, German and Dutch bone substudy of the TEAM trial. Patients treated on exemestane showed a more rapid decrease in BMD at the lumbar spine and total hip initially (−2.6 and −1.3 %, respectively), followed by a decreased phase of bone loss between 12 and 24 months (−3.5 and −3.3 %, respectively) (Jones et al. 2008). The results from our substudy are consistent with those reported in the discussed trials; none of these trials evaluated the effect of the compliance on BMD.

In the past, compliance to adjuvant endocrine treatment in women with early BC was not considered to be a major concern because those women facing a serious life threatening disease and because therapy is usually well tolerated and considered as being very effective. Contradictory to this perception of physicians and patients, recent studies indicated a clinically relevant decline in adherence to AI and tamoxifen treatment followed by an increase in BC recurrence and mortality as soon as within the first year (Murphy et al. 2012; Partridge et al. 2003; 2006).

Apparently, maximum effect of treatment is confined to the compliance of the patient with respect to the consistent drug intake of prescribed medications. Reduced compliance may be related to unnecessary change of treatment, increased side effects, longer hospitalization with regard to failure of treatment and overall diminished clinical outcome (Ruddy and Partridge 2009). Several studies in the past investigated adherence in patients receiving tamoxifen using self-reported evaluation or database claim methods reporting adherence rates ranging from 65 to 85 % with regard to a follow-up between 3 and 5 years (Barron et al. 2007; Demissie et al. 2001; Fink et al. 2004; Lash et al. 2006; Murphy et al. 2012; Owusu et al. 2008; Partridge et al. 2008).

Hereby, treatment side effects as well as switching from one to another treatment were negatively associated with adherence and/or persistence (DiIorio et al. 2008; Golin et al. 2006; Murphy et al. 2012; Schmaling et al. 2000). According to six studies, the approach to explain patients expected adverse effects of treatment did not affect their adherence. It has been stated that short-term adherence can be improved with a variety of interventions, but even the most effective interventions did not lead to large improvements in adherence and treatment outcomes in the long run. Therefore, the authors concluded that high priority should be given to fundamental and applied research concerning innovations to assist patients to follow medication prescriptions for long-term medical disorders (Haynes et al. 2005).

The limitations of the present study are the small sample size due to the fact of the relatively small number of the overall cohort willing to participate in the bone substudy as well as a high dropout rate. There were no fractures reported in the compliant as well as in the non-compliant group, again due to the small sample size and the median follow-up time.

Conclusions

In conclusion, compliant patients treated with Anastrozole experience more rapid loss of BMD during the first 12 months of treatment; the rate of bone loss then stabilized between 12 and 24 months of treatment at the lumbar spine but continuous to decrease at the total hip in comparison with non-compliant patients. This strengthens the importance of further effort to increase long-term compliance which should improve therapeutic outcome and efficiency.

Acknowledgments

This study was sponsored by an unrestricted research grand by Astra Zeneca Germany.

Conflict of interest

Peyman Hadji has received honoraria, unrestricted educational grants, and research funding from the following companies: Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi Aventis and Wyeth. Volker Ziller, Dana Knöll, Ioannis Kyvernitakis, Olaf Hars and Matthias Kalder have no conflict of interest with regard to this study. The corresponding and the senior author had full access to all data and final responsibility for the decision to submit for publication.

References

  1. Banning M (2012) Adherence to adjuvant therapy in post-menopausal breast cancer patients: a review. Eur J Cancer Care (Engl) 21:10–19 [DOI] [PubMed] [Google Scholar]
  2. Barron TI, Connolly R, Bennett K, Feely J, Kennedy MJ (2007) Early discontinuation of tamoxifen: a lesson for oncologists. Cancer 109:832–839 [DOI] [PubMed] [Google Scholar]
  3. Blake GM, Fogelman I (1997) Interpretation of bone densitometry studies. Semin Nucl Med 27:248–260 [DOI] [PubMed] [Google Scholar]
  4. Coates AS, Keshaviah A, Thurlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Lang I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A (2007) Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1–98. J Clin Oncol 25:486–492 [DOI] [PubMed] [Google Scholar]
  5. Coleman RE, Banks LM, Girgis SI, Kilburn LS, Vrdoljak E, Fox J, Cawthorn SJ, Patel A, Snowdon CF, Hall E, Bliss JM, Coombes RC (2007) Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol 8:119–127 [DOI] [PubMed] [Google Scholar]
  6. Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350:1081–1092 [DOI] [PubMed] [Google Scholar]
  7. Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM (2007) Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 369:559–570 [DOI] [PubMed] [Google Scholar]
  8. Demissie S, Silliman RA, Lash TL (2001) Adjuvant tamoxifen: predictors of use, side effects, and discontinuation in older women. J Clin Oncol 19:322–328 [DOI] [PubMed] [Google Scholar]
  9. Dezentje VO, van Blijderveen NJ, Gelderblom H, Putter H, van Herk-Sukel MP, Casparie MK, Egberts AC, Nortier JW, Guchelaar HJ (2010) Effect of concomitant CYP2D6 inhibitor use and tamoxifen adherence on breast cancer recurrence in early-stage breast cancer. J Clin Oncol 28:2423–2429 [DOI] [PubMed] [Google Scholar]
  10. DiIorio C, McCarty F, Resnicow K, McDonnell HM, Soet J, Yeager K, Sharma SM, Morisky DE, Lundberg B (2008) Using motivational interviewing to promote adherence to antiretroviral medications: a randomized controlled study. AIDS Care 20:273–283 [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717 [DOI] [PubMed] [Google Scholar]
  12. Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J, Mackey JR, Beckmann MW, Clack G (2008) Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol 26:1051–1057 [DOI] [PubMed] [Google Scholar]
  13. Eastell R, Adams J, Clack G, Howell A, Cuzick J, Mackey J, Beckmann MW, Coleman RE (2011) Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. Ann Oncol 22:857–862 [DOI] [PubMed] [Google Scholar]
  14. Fallowfield L (2005) Acceptance of adjuvant therapy and quality of life issues. Breast 14:612–616 [DOI] [PubMed] [Google Scholar]
  15. Fink AK, Gurwitz J, Rakowski W, Guadagnoli E, Silliman RA (2004) Patient beliefs and tamoxifen discontinuance in older women with estrogen receptor–positive breast cancer. J Clin Oncol 22:3309–3315 [DOI] [PubMed] [Google Scholar]
  16. Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M (2008) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 9:45–53 [DOI] [PubMed] [Google Scholar]
  17. Golin CE, Earp J, Tien HC, Stewart P, Porter C, Howie L (2006) A 2-arm, randomized, controlled trial of a motivational interviewing-based intervention to improve adherence to antiretroviral therapy (ART) among patients failing or initiating ART. J Acquir Immune Defic Syndr 42:42–51 [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL (2003) A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349:1793–1802 [DOI] [PubMed] [Google Scholar]
  19. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 97:1262–1271 [DOI] [PubMed] [Google Scholar]
  20. Hadji P (2008) Menopausal symptoms and adjuvant therapy-associated adverse events. Endocr Relat Cancer 15:73–90 [DOI] [PubMed] [Google Scholar]
  21. Hadji P (2009) Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Crit Rev Oncol Hematol 69:73–82 [DOI] [PubMed] [Google Scholar]
  22. Hadji P (2010) Improving compliance and persistence to adjuvant tamoxifen and aromatase inhibitor therapy. Crit Rev Oncol Hematol 73:156–166 [DOI] [PubMed] [Google Scholar]
  23. Hadji P, Gottschalk M, Ziller V, Kalder M, Jackisch C, Wagner U (2007) Bone mass and the risk of breast cancer: the influence of cumulative exposure to oestrogen and reproductive correlates. Results of the Marburg breast cancer and osteoporosis trial (MABOT). Maturitas 56:312–321 [DOI] [PubMed] [Google Scholar]
  24. Hadji P, Hartenfels M, Kyvernitakis J, Hars O, Baumann KH, Kalder M (2012) Recommendations for antiresorptive therapy in postmenopausal patients with breast cancer: marburg AIBL Guideline Evaluation Study (MAGES). Breast Cancer Res Treat 133:1089–1096 [DOI] [PubMed] [Google Scholar]
  25. Haynes RB, Yao X, Degani A, Kripalani S, Garg A, McDonald HP (2005) Interventions to enhance medication adherence. Cochrane.Database.Syst.Rev.CD000011 [DOI] [PubMed]
  26. Hershman DL, Kushi LH, Shao T, Buono D, Kershenbaum A, Tsai WY, Fehrenbacher L, Gomez SL, Miles S, Neugut AI (2010) Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol 28:4120–4128 [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hershman DL, Shao T, Kushi LH, Buono D, Tsai WY, Fehrenbacher L, Kwan M, Gomez SL, Neugut AI (2011) Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat 126:529–537 [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62 [DOI] [PubMed] [Google Scholar]
  29. Jones S, Stokoe C, Sborov M, Braun M, Ethirajan S, Kutteh L, Pippen J, Patel M, Paul D, Blum JL, Holmes FA, Myron MC, Cantrell J, Hartung NL, Look RM, Di SE, Davis JC, Ilegbodu D, Asmar L (2008) The effect of tamoxifen or exemestane on bone mineral density during the first 2 years of adjuvant treatment of postmenopausal women with early breast cancer. Clin Breast Cancer 8:527–532 [DOI] [PubMed] [Google Scholar]
  30. Kalder M, Jager C, Seker-Pektas B, Dinas K, Kyvernitakis I, Hadji P (2011) Breast cancer and bone mineral density: the Marburg Breast Cancer and Osteoporosis Trial (MABOT II). Climacteric 14:352–361 [DOI] [PubMed] [Google Scholar]
  31. Kanis JA, Devogelaer JP, Gennari C (1996) Practical guide for the use of bone mineral measurements in the assessment of treatment of osteoporosis: a position paper of the European foundation for osteoporosis and bone disease. The Scientific Advisory Board and the Board of National Societies. Osteoporos Int 6(3):256–261 [DOI] [PubMed] [Google Scholar]
  32. Lash TL, Fox MP, Westrup JL, Fink AK, Silliman RA (2006) Adherence to tamoxifen over the five-year course. Breast Cancer Res Treat 99:215–220 [DOI] [PubMed] [Google Scholar]
  33. Love RR, Mazess RB, Barden HS, Epstein S, Newcomb PA, Jordan VC, Carbone PP, DeMets DL (1992) Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 326:852–856 [DOI] [PubMed] [Google Scholar]
  34. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW (2012) Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat 134:459–478 [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Owusu C, Buist DS, Field TS, Lash TL, Thwin SS, Geiger AM, Quinn VP, Frost F, Prout M, Yood MU, Wei F, Silliman RA (2008) Predictors of tamoxifen discontinuation among older women with estrogen receptor-positive breast cancer. J Clin Oncol 26:549–555 [DOI] [PubMed] [Google Scholar]
  36. Partridge AH (2006) Non-adherence to endocrine therapy for breast cancer. Ann Oncol 17:183–184 [DOI] [PubMed] [Google Scholar]
  37. Partridge AH, Wang PS, Winer EP, Avorn J (2003) Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol 21:602–606 [DOI] [PubMed] [Google Scholar]
  38. Partridge AH, LaFountain A, Mayer E, Taylor BS, Winer E, snis-Alibozek A (2008) Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol 26:556–562 [DOI] [PubMed] [Google Scholar]
  39. Ruddy KJ, Partridge AH (2009) Adherence with adjuvant hormonal therapy for breast cancer. Ann Oncol 20:401–402 [DOI] [PubMed] [Google Scholar]
  40. Schmaling KB, Afari N, Blume AW (2000) Assessment of psychological factors associated with adherence to medication regimens among adult patients with asthma. J Asthma 37:335–343 [DOI] [PubMed] [Google Scholar]
  41. Waterhouse DM, Calzone KA, Mele C, Brenner DE (1993) Adherence to oral tamoxifen: a comparison of patient self-report, pill counts, and microelectronic monitoring. J Clin Oncol 11:1189–1197 [DOI] [PubMed] [Google Scholar]
  42. Ziller V, Kalder M, Albert US, Holzhauer W, Ziller M, Wagner U, Hadji P (2009) Adherence to adjuvant endocrine therapy in postmenopausal women with breast cancer. Ann Oncol 20:431–436 [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES