Matthias Kalder

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.

Use of complementary and alternative medicine during pregnancy and delivery.

PurposeTo assess the use of complementary and alternative medicine (CAM) during pregnancy and birth and the reasons behind it from the patient’s perspective.MethodsIn a prospective study, we assessed the use of CAM before and during pregnancy as well as during delivery in women by means of a self-report questionnaire.ResultsSome 205 patients completed the questionnaire at a response rate of 43.2% (205/475) and 104 women used CAM during pregnancy, especially homoeopathy, acupuncture, and phytotherapy. Stepwise regression analysis identified CAM use prior to pregnancy, greater income, and nationality as the most important predictors of CAM use.ConclusionsIn accordance with earlier studies from Germany, we determined the most important methods used in the field of obstetrics. Interestingly, these are not evidence-based and those methods which are evidence-based are not now used. Also, the predictors of CAM use in pregnancy were similar to those in oncology. Future studies should focus on the safety and efficacy of CAM in pregnancy.

The effect of exemestane or tamoxifen on markers of bone turnover: Results of a German sub-study of the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial

Adjuvant treatment of breast cancer with aromatase inhibitors has been associated with increased bone loss. In this study, postmenopausal patients with oestrogen receptor positive breast cancer were randomised to exemestane for 5 years or tamoxifen for 2-2.5 years, followed by exemestane for 2-2.5 years. Levels of bone formation markers (bone specific alkaline phosphatase, amino terminal propeptide of type I procollagen, osteocalcin), and the bone resorption marker (carboxyterminal crosslinked telopeptide of type I collagen), were assessed at baseline and after 3, 6 and 12 months of treatment. Exemestane (n=78) resulted in increases from baseline in all bone turnover marker levels at all timepoints. In contrast, levels of all bone marker turnovers decreased with tamoxifen (n=83). Differences between tamoxifen and exemestane were statistically significant for all bone turnover markers at all timepoints. In conclusion, exemestane results in increases in markers of bone formation and resorption, while decreases are observed with tamoxifen.

The influence of chemotherapy on bone mineral density, quantitative ultrasonometry and bone turnover in pre-menopausal women with breast cancer

INTRODUCTION The effects of doxorubicin/cyclophosphamide (A/C; 6 cycles) chemotherapy on bone mineral density (BMD), quantitative ultrasonography (QUS) and bone turnover markers in pre-menopausal women with oestrogen receptor-negative breast cancer (BC) were compared with age-matched controls. METHODS Among 106 women (BC=53, controls=53), BMD (spine and hip), QUS (calcaneus and phalanges) and bone marker levels were measured at baseline, 6 and 12 months. Correlations between parameters were determined by Spearmans rho. RESULTS All BC patients became amenorrhoeic after chemotherapy and remained so for the duration of treatment. BC patients had significant bone loss at all sites (P.005) and significant increases in bone turnover (P.05). There were significant correlations between BMD, QUS and bone markers (P.05). CONCLUSIONS Results confirm A/Cs deleterious influence on bone health in pre-menopausal women with BC and established QUSs utility for monitoring bone effects. Large-scale longitudinal studies are needed to further understand and prevent bone changes following chemotherapy.

Effects of Exemestane and Tamoxifen Treatment on Bone Texture Analysis Assessed by TBS in Comparison With Bone Mineral Density Assessed by DXA in Women With Breast Cancer

We performed an analysis of a substudy of the randomized Tamoxifen Exemestane Adjuvant Multinational trial to determine the effects of exemestane (EXE) and tamoxifen (TAM) adjuvant treatment on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry compared with the trabecular bone score, a novel grey-level texture measurement that correlates with 3-dimensional parameters of bone texture in postmenopausal women with hormone receptor-positive breast cancer for the first time. In total, 36 women were randomized to receive TAM (n = 17) or EXE (n = 19). Patients receiving TAM showed a mean increase of BMD in lumbar spine from baseline of 1.0%, 1.5%, and 1.9% and in trabecular bone score of 2.2%, 3.5%, and 3.3% at 6-, 12-, and 24-mo treatment, respectively. Conversely, patients receiving EXE showed a mean decrease from baseline in lumbar spine BMD of -2.3%, -3.6%, and -5.3% and in trabecular bone score of -0.9%, -1.7%, and -2.3% at 6-, 12-, and 24-mo treatment, respectively. Changes in trabecular bone score from baseline at spine were also significantly different between EXE and TAM: p = 0.05, 0.007, and 0.006 at 6, 12, and 24 mo, respectively. TAM induced an increase in BMD and bone texture analysis, whereas EXE resulted in decreases. The results were independent from each other.

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.

Impact of a single perioperative dose of dexamethasone on the incidence of surgical site infections: A case–control study

Aims:  Dexamethasone is recommended in several international guidelines to prevent postoperative nausea and vomiting, a problem especially frequent in gynecological patients. Despite the increasing use of dexamethasone for this indication there are limited data concerning potential harmful effects of corticosteroids in surgical patients, especially the potential negative impact on wound healing and surgical site infection (SSI). This case–control study was conducted to look for potentially harmful effects of a single perioperative dose of dexamethasone with respect to the occurrence of SSI in gynecological and obstetric surgery patients.

Anti‐emetic prophylaxis with oral tropisetron and/or dexamethasone

Background  The corticosteroid dexamethasone and the serotonine3‐antagonist tropisetron are both effective drugs for the prophylaxis of post‐operative nausea and vomiting (PONV) when given intravenously. The aim of this trial was to evaluate the oral use of both drugs as part of a routine oral premedication and to compare their single and combined effectiveness.