P. Hadji

Adherence to adjuvant endocrine therapy in postmenopausal women with breast cancer

BACKGROUND The level of adherence of various pharmacological therapies in chronic diseases varies, but is predominantly low. With tamoxifen (TAM), 23% and 50% nonadherence after 1 and 4 years have been reported. Day-to-day clinical observation suggests that adherence may even be lower with aromatase inhibitors, but limited data exist on the situation in daily clinical routine. The aim of this study was to evaluate the rate of adherent patients in a randomly selected sample of postmenopausal women with primary breast cancer, who had been assigned to an adjuvant endocrine treatment with TAM or anastrozole (ANA). MATERIALS AND METHODS We investigated a random sample of 100 postmenopausal women with breast cancer (50 TAM and 50 ANA) who had received surgery for their primary breast cancer at our hospital in 2004/2005 and thereafter had been assigned to an adjuvant endocrine treatment. We evaluated the adherence rate with a detailed questionnaire and additionally carried out a retrospective prescription check of the hospital chart as well as calling the local physicians of our patients. A patient was counted as adherent with a self-reported tablet intake of 80% or more and if a medication possession ratio of 80% or more was achieved. RESULTS Regarding the baseline characteristics, a significant difference in mean age was noticed in women on ANA versus TAM [65 (+/-3) and 72 (+/-3); P<0.001]. All women on TAM and ANA reported to be adherent (100%). After controlling for prescriptions, only 40 (80%) and 27 (69%) of the women on TAM and ANA were still classified as adherent (P<0.01 and P<0.01 versus self-report). We found no significant correlation of adherence to any baseline characteristics or side-effects in a logistic regression model. CONCLUSIONS An important goal of any therapeutic intervention is to achieve comparable efficacy in routine clinical practice to that demonstrated in randomised clinical trials. However, a similar magnitude of adherence will be necessary in routine clinical practice to assure comparable clinical effects. Our results further support the data on suboptimal adherence of women with breast cancer on adjuvant TAM treatment. Here, we evaluated for the first time the patient reported and real-world adherence on adjuvant ANA and were able to show a similarly low adherence compared with TAM. More prospective studies are needed to increase our understanding of the underlying reasons for nonadherence in women with breast cancer.

The Patient's Anastrozole Compliance to Therapy (PACT) Program: a randomized, in-practice study on the impact of a standardized information program on persistence and compliance to adjuvant endocrine therapy in postmenopausal women with early breast cancer

BACKGROUND Compliance and persistence are often overlooked in adjuvant breast cancer treatment. PATIENTS AND METHODS PACT was a prospective, multicenter, randomized, open, parallel-group study assessing whether educational materials (EMs) enhanced compliance with aromatase inhibitor (AI) therapy in postmenopausal women with early, hormone-receptor-positive (HR+) breast cancer. The primary end points were compliance (proportion taking ≥ 80% anastrozole) at 12 months and persistence (proportion reporting anastrozole intake during the study period). RESULTS Four thousand eight hundred and forty-four patients were randomly assigned 1:1 to receive standard therapy or standard therapy with EMs. There was no difference between arms in compliance (N = 2740; 88.5%/88.8%, respectively, P = 0.81) or persistence rates (N = 2740; 40.5%/43.0%, respectively, P = 0.18). Modified end point analyses found no differences in compliance between arms based on the classification of: (i) patients with missing documentation or follow-up visit <9 months as non-compliant (N = 4397, P = 0.15); (ii) patients with early (≤ 292 days) 12-month follow-up documentation excluded (N = 4091, P = 0.19); (iii) patients reaching ≥ 80% compliance during individual follow-up as compliant (N = 4397, P = 0.26). Modified persistence analyses found no difference between arms (N = 4397, P = 0.37). CONCLUSIONS Addition of EMs to standard therapy did not significantly affect compliance and persistence with adjuvant anastrozole. CLINICALTRIALS ID: NCT00555867.

COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy

BACKGROUND This prospective study evaluated the relationship between arthralgia and compliance during the first year of adjuvant anastrozole therapy in postmenopausal women with hormone receptor-positive early breast cancer. PATIENTS AND METHODS COMPliance and Arthralgia in Clinical Therapy (COMPACT) was an open-label, multicenter, noninterventional study conducted in Germany. Patients had started adjuvant anastrozole 3-6 months before the study start. The primary end points were arthralgia, compliance, and the relationship between compliance and arthralgia, assessed at specific time points. RESULTS Overall, 1916 patients received upfront anastrozole. Mean arthralgia scores were increased from baseline at each visit up to 9 months. Compliance with anastrozole therapy gradually decreased over time from baseline to 9 months (P<0.001). At 9 months, investigators estimated that >95% of patients were compliant versus patient reports of <70%. There was a significant association between arthralgia mean scores and noncompliance at 6 months (P<0.0001), 9 months (P<0.0001), and overall (P<0.0001). Over time, new events or impairment of existing arthralgias were reported in 14% (3 months), 11% (6 months), and 9% (9 months) of patients. CONCLUSION Arthralgia is important in the clinical management of women with early breast cancer and may contribute to noncompliance and clinical outcomes. CLINICALTRIALSGOV IDENTIFIER NCT00857012.

Influence of pregnancy and breast-feeding on quantitative ultrasonometry of bone in postmenopausal women

Objective: Reproductive factors such as parity and breast-feeding may be associated with low bone mass and osteoporotic fractures in later years. In this study, os calcis quantitative ultrasonometry was used to elucidate the relationship between parity, lactation and bone mass in postmenopausal women. Design: This was a comparison study using subsequent matched pairs analysis as well as multiple linear regression analysis. The study was carried out at five centers in Germany. The study included 2080 postmenopausal women (age (mean ± SD) 58.8 ± 8.2 years), who were attending for routine check-up and in whom diseases and drug treatments known to affect bone metabolism had been excluded. Methods and outcome measures: Women underwent quantitative ultrasonometry (QUS) measurement at the heel. Values of the ultrasonometry variables –speed of sound, broadband ultrasound attenuation and stiffness index –were calculated and compared for nulliparous and parous women and for women who had and had not breast-fed. Because of some significant intergroup differences, and to determine any effect of the number of live births and the duration of breast-feeding on ultrasonometry results, second analyses were undertaken using equally sized samples, matched for possible confounding variables such as age and body mass index (matched pairs). In these analyses, nulliparous women were compared with parous women, grouped according to number of live births, and women who had never breast-fed were compared with women who had breast-fed, grouped according to duration of breast-feeding. Furthermore, a multiple linear regression analysis was performed to examine the combined effects of reproductive factors on QUS variables. Results: No statistically significant associations were found between ultrasonometry variables and parity or breast-feeding, even after controlling for confounding variables in matched-pairs analysis or in a multiple linear regression analysis.

Prevalence of menopausal symptoms and their influence on adherence in women with breast cancer.

Abstract Objectives The use of aromatase inhibitors for the adjuvant treatment of breast cancer may affect the quality of life of patients, as well as adherence to treatment. Methods Here we report the 2-year results of the 180 patients in the COMPAS study. This is the first randomized, controlled study reporting on menopausal symptoms under endocrine treatment with aromatase inhibitors in breast cancer patients, based on the Menopause Rating Scale. We analyzed the prevalence of menopausal symptoms as well as their associations with patient adherence. Results Baseline characteristics showed no significant differences among the control and the intervention groups. The majority of women experienced the symptoms at various severities. Overall, we found an increase in the prevalence of hot flushes, sleep disorders, bladder problems, dryness of the vagina as well as of joint and muscular discomfort between the 12- and 24-month visits. In compliant patients, all symptoms except for vaginal dryness improved between the 12- and 24-month visits while, in non-compliant women, hot flushes, irritability, dryness of the vagina as well as joint and muscular discomfort deteriorated. When comparing compliant and non-compliant patients, we found a significant difference only for anxiety (p = 0.028) in the 12-month analysis, as well as a large but non-significant difference for heart discomfort (p = 0.089) in the 24-month visit. Conclusions Our results indicate that the majority of women treated with aromatase inhibitors are experiencing menopausal symptoms at various severities. We showed that the mean symptom values in compliant patients improve with longer therapy duration. Furthermore, anxiety correlates with better compliance, while heart discomfort may lead to therapy discontinuation.

Adherence and persistence in patients with severe osteoporosis treated with teriparatide.

Abstract Introduction: Medical intervention plays a key role in the treatment of postmenopausal osteoporosis and patients’ adherence to therapy is essential for optimal clinical outcomes. While adherence in RCTs is usually around 70–90%, a previous study showed that in clinical practice only 27.8% and 46.5% of the women on oral daily vs. weekly alendronate were still on treatment after 12 months. Data on adherence to teriparatide (TPTD) treatment of severe postmenopausal osteoporosis are available from only few countries. This study assessed adherence and persistence with TPTD in Germany. Material and methods: A sample of 50 women with severe postmenopausal osteoporosis treated with TPTD in accordance to the German osteoporosis guidelines was included. Treatment was initiated 12–24 months before recruitment. Patient self report was assessed using a validated questionnaire. In addition medication possession ratio (MPR) was calculated by counting prescription refills, and therefore all physicians who were treating the patients for any disease were contacted. Patients were classified adherent at 12 months of therapy if self-reported adherence and an MPR of ≥80% were achieved. Persistence was calculated in months and analysed with a Kaplan–Meier estimate. Results: Apart from a significantly lower age at menopause in the adherent group (46.1 vs. 50.0; p < 0.006) there were no significant differences in baseline demographics between adherent and non-adherent patients. After 12 months, 80% of the patients treated with TPTD were adherent, while 20% were non-adherent. A significant correlation with treatment adherence was found for self-reported medication tolerability (p < 0.001). Furthermore 79% of patients were persistent after 12 months. Conclusion: These results indicate that more patients seem to be adherent and persistent with TPTD than with oral treatments of postmenopausal osteoporosis. As these patients suffered from severe osteoporosis and sustained several fragility fractures, the generalisability of our retrospective study analysing a small sample is limited. The major factor that reduced adherence and persistence was tolerability. These findings are of practical relevance as numerous studies on antiresorptive therapies have shown that high adherence and persistence were needed to ensure an optimal therapeutic outcome.

The evolution of selective estrogen receptor modulators in osteoporosis therapy

Selective estrogen receptor modulators (SERMs), which exhibit estrogen receptor agonist or antagonist activity based on the target tissue, have evolved through multiple generations for the prevention and/or treatment of postmenopausal osteoporosis. An ideal SERM would protect bone without stimulating the breast or endometrium. Raloxifene, lasofoxifene, and bazedoxifene have demonstrated unique preclinical profiles. Raloxifene, lasofoxifene, and bazedoxifene have shown significant reduction in the risk of vertebral fracture and improvement in bone mineral density versus placebo in postmenopausal women with osteoporosis. Raloxifene has been shown to reduce the risk of non-vertebral fractures in women with severe prevalent fractures at baseline. Lasofoxifene 0.5 mg, but not lasofoxifene 0.25 mg, has shown reduction in the incidence of non-vertebral fractures. Bazedoxifene 20 mg has been associated with a significant reduction in the risk of non-vertebral fracture versus placebo and raloxifene 60 mg in women at higher baseline fracture risk. Neither raloxifene, lasofoxifene, nor bazedoxifene has shown an increase in the incidence of endometrial hyperplasia or carcinoma. All SERMs have been associated with increased venous thromboembolic events and hot flushes. SERMs are effective alternatives for women who cannot tolerate or are unwilling to take bisphosphonates and may be appropriate for women at higher risk of fracture, particularly younger women who expect to remain on therapy for many years and are concerned about the long-term safety of bisphosphonates.

The Impact of Breast Care Nurses on Patients' Satisfaction, Understanding of the Disease, and Adherence to Adjuvant Endocrine Therapy

Background: Breast care nurses (BCNs) are specialized caregivers in certified breast cancer center teams. The impact of a BCN’s work remains unknown. Patients and Methods: The role of BCN care was evaluated in a post-discharge mail survey of 360 patients. Results: A total of 207 (87%) of 237 (66%) returned questionnaires were analyzed; 171 (83%) patients had BCN contact, 36 (17%) did not. The mean global quality of life scores (EORTC-QLQ-C30) were 66.3 for women with contact to a BCN versus 62.5 for women without such contact (p < 0.05). Women with a BCN contact had better results than women without (p < 0.001) for the following parameters: receipt of information material (84 vs. 64%), information about hospital procedures (93 vs. 72%) and treatment plan (91 vs. 63%), and knowledge of own tumor hormone receptor status (83 vs. 53%). Medication adherence correlated with the knowledge about the tumor hormone receptor status and was significantly higher in women having contact with a BCN (79 vs. 56%). The high recommendation rate (81%) reflects the high level of satisfaction with BCNs. A qualitative analysis of comments and suggestions identified aspects to improve BCN services. Conclusions: BCN improve satisfaction and treatment adherence in breast cancer patients.

Comparison of dual-energy X-ray absorptiometry with six quantitative ultrasonometry devices in women with hip fractures

Abstract Objectives Dual-energy X-ray absorptiometry (DXA) is the gold standard for assessment of bone mineral density, an important risk factor for osteoporotic fractures. Recent reports suggest that quantitative ultrasonometry (QUS) is able to predict fractures; however, only limited data in women with hip fractures are available. Methods We examined 91 postmenopausal women who had sustained an osteoporosis-related hip fracture within the past 7 days using DXA and six different QUS devices and compared them with 91 healthy age-matched controls. Results Femoral neck (FN), total hip (TH) and lumbar spine (LS) T-scores were lower in women with hip fractures compared to matched controls: − 2.38 vs. − 1.64 (p < 0.001), − 2.36 vs. − 1.44 (p < 0.001) and − 2.05 vs. − 1.50 (p = 0.41), respectively. The T-scores of the Achilles, Sahara, InSight and Omnisence QUS devices were also lower in patients with hip fractures compared to matched controls: − 3.20 vs. − 2.36 (p < 0.001), − 2.196 vs. − 1.761 (p = 0.005), − 2.631 vs. − 1.849 (p < 0.001), − 3.707 vs. − 3.030 (p = 0.032), respectively. However, the T-scores of the DBM and QUS-2 did not differ between the two groups: − 4.543 vs. − 4.324 (p = 0.352) and − 1.7 vs. − 2.0 (p = 0.465), respectively. Compared to DXA (hip), the odds ratios of the Achilles, InSight and Sahara were comparable, while the odds ratios of the DBM, Omnisence and QUS-2 were significantly lower (p ≤ 0.05). Conclusions Compared to DXA, the Achilles, Sahara and InSight QUS devices showed similar hip fracture discrimination while the DBM, Omnisence and QUS-2 did not. Therefore, some QUS devices are able to identify a clinically meaningful risk factor in women at high risk of hip fracture.

Successful treatment of 1-34 parathyroid hormone (PTH) after failure of bisphosphonate therapy in a complex case of pregnancy associated osteoporosis and multiple fractures.

INTRODUCTION Pregnancy associated osteoporosis (PAO) was first reported almost half a century ago. The most common symptom is acute lower back pain due to vertebral fractures in the last trimester or immediately after birth. PATIENT We present a case involving a female patient born in 1971 (gravida II, para I) with a history of PAO. In April 2000 at the age of 28 years, she delivered a son and breastfed him for 4 months. A first magnetic resonance tomography (MRT) screening in June 2000 showed osteoporotic fractures at lumbar vertebra 1-4. Therefore, the patient received oral alendronate therapy. In May 2001, a second MRT exhibited burst fracture of thoracic 8, end-plate fracture of thoracic 11, 12, lumbar 2-5 and compression fracture of lumbar 1. The oral therapy was switched to ibandronate (3 mg) intravenously every 3 months. An X-ray in December 2002 showed 3 new additional end-plate fractures at thoracic 4, 6 and 7. Ibandronate was discontinued in September 2004 and the patient received daily subcutaneous (s. c.) injections of 1-34 PTH in September 2005. RESULTS After starting 1-34 PTH treatment for 18 months, a further increase in bone mineral density (BMD) was achieved without any further fracture. CONCLUSION We presented for the first time a case of severe PAO with 11 spine fractures. We observed an unsatisfactory effect of oral and i. v. bisphosphonates in combination with adequate calcium and vitamin D supplementation. The treatment with 1-34 PTH showed an increase in BMD with no further fractures.